Publications
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Søraas, Arne Vasli Lund; Engvig, Andreas; Alnæs, Dag; Karim, Lana Nagmadin; Danilova, Elena & Istre, Mette Stausland
[Show all 17 contributors for this article]
(2026).
Interstitial fluid rejuvenation through young-donor plasma exchange in cognitively impaired patients: a pilot safety and feasibility study.
GeroScience.
ISSN 2509-2715.
doi:
10.1007/s11357-026-02435-0.
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Heterochronic parabiosis improves physiological and cognitive function in aging rodents; these benefits appear to be derived from the removal of aged blood plasma components and the addition of younger ones. In humans, removing plasma from older individuals with Alzheimer’s disease (AD) and replacing it with saline and albumin delayed cognitive deterioration in a large clinical trial. However, mimicking heterochronic parabiosis in humans by removing large volumes of a patient’s blood plasma and replacing it with plasma from young and healthy donors has not been tested. Here, we have performed a pilot study to characterize the feasibility and safety of such a procedure, replacing between 16 and 26 L of patient blood plasma with young (ages 18–24) donor blood plasma for twelve patients who recently received a diagnosis of mild cognitive impairment with biomarker evidence of AD. The dose and time interval between plasma exchanges was tailored to maximize equilibration of donor plasma components into the interstitial fluid, with the aim of achieving what we term interstitial rejuvenation. We explored three permutations of a plasma exchange protocol with different treatment intensities and doses, each performed on three to five patients. We present data on safety, feasibility, patient burden, resource use of the treatments, preliminary measurements of clinical variables, and short-term cognitive trajectories in the patients. The procedures were feasible, and the adverse events observed were consistent with known risks of plasma exchange, supporting further investigation of treatment efficacy in a larger controlled trial. This safety and feasibility study was first registered 22 December 2023 at ClinicalTrials.gov and given the identifier NCT06234436.
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Kildal, Anders Benjamin; Ueland, Thor; Mirlashari, Mohammad Reza; Nissen-Meyer, Lise Sofie; Granerud, Beathe Kiland & Riise, Anne Margarita Dyrhol
[Show all 44 contributors for this article]
(2026).
Serial blood serum measurements of calprotectin and deoxyribonuclease in COVID-19 patients during hospitalization and recovery until one year: a prospective, multicenter, observational study.
BMC Infectious Diseases.
26.
doi:
10.1186/s12879-026-12939-x.
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Objectives: To examine circulating calprotectin and deoxyribonuclease (DNase) serum levels during hospitalization in COVID-19 patients, their continuity post-discharge and dynamics in relation to disease severity.
Methods: Serum levels were measured in samples collected from 252 COVID-19 patients during hospitalization (admission, days 3–5 and 7–10), at 3 months and after 1 year, and related to admission to intensive care unit (ICU) or high dependency unit (HDU), and 60-day total mortality.
Results: During hospitalization, calprotectin and DNase levels were significantly elevated compared to healthy controls (HC). Calprotectin was increased in ICU/HDU patients compared to those at wards during hospitalization and in non-survivors compared to survivors during prolonged hospitalization. High calprotectin levels at admission were associated with male sex, PaO2/FiO2 ratio and national COVID-19 wave 2 and 3 compared to wave 1. High admission levels of both calprotectin and ferritin were associated with an approximately twofold higher odds ratio for ICU/HDU admission than either marker alone. DNase was lower at admission in non-survivors compared to survivors. Post-discharge, DNase but not calprotectin levels remained elevated extending to 1-year follow-up compared to HC.
Conclusions: COVID‑19 non‑survivors showed persistently higher calprotectin levels during prolonged hospitalization, and elevated admission calprotectin was associated with later pandemic waves and poorer oxygenation. Incorporating calprotectin with ferritin improved prediction of ICU/HDU admission. DNase levels were lower at admission in non‑survivors, while overall DNase remained elevated from hospitalization through 1‑year follow‑up compared with HC, suggesting a possible role in long‑term COVID‑19–related immune alterations.
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Haugen, Morten; Nissen-Meyer, Lise Sofie; Strand, Tor Arne & Magnussen, Karin
(2025).
The effect of plasma donation frequency on total serum protein, immunoglobulin G and donor safety: A non-inferiority randomized controlled trial.
Vox Sanguinis.
ISSN 0042-9007.
120(12),
p. 1205–1215.
doi:
10.1111/vox.70105.
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Background and objectives: The safety of varying plasma donation frequencies remains unclear. This non-inferiority randomized controlled trial investigated the effect of plasma donation frequency on total serum protein (TSP), immunoglobulin G (IgG) concentrations, additional biomarkers, adverse events (AEs) and psychological distress.
Materials and methods: In this trial, 120 male donors were randomized into three groups: high-frequency plasma donors (HFPDs, three times every 2 weeks), regular-frequency plasma donors (RFPDs, once every 2 weeks) and a control group (whole blood donation every 3 months). Blood samples were collected biweekly from baseline until the last donation in Week 16 and 4 weeks after the last donation.
Results: HFPDs completed median (range) 21.5 (1-24), RFPDs 8 (1-8) and controls 2 (1-2) donations. HFPDs had lower concentrations of TSP and IgG compared to controls, with a mean difference (95% confidence interval [CI]) of -5.5 g/L (-7.4, -3.6) and -2.8 g/L (-3.8, -1.8), respectively. Within-group analysis revealed significant reductions, which increased with the frequency of donations, in TSP, IgG, IgG subclasses, immunoglobulin M (IgM), immunoglobulin A (IgA), ferritin and haemoglobin. Many of the biomarkers required more than 4 weeks to return to baseline levels. Only mild AEs were reported, and plasma donation frequency had no effect on psychological distress.
Conclusion: High- and regular-frequency plasmapheresis substantially reduces concentrations of TSP, IgG and other biomarkers, with greater reductions at higher donation frequencies. Further research is needed to assess the long-term health implications of frequent plasma donation.
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Mahmood, Faiza; Hetland, Geir; Mirlashari, Mohammad Reza & Nissen-Meyer, Lise Sofie
(2025).
IgE sensitization profiles to food, inhalant and insect venom in Norwegian blood donors and their impact on blood transfusions.
Scandinavian Journal of Immunology.
ISSN 0300-9475.
101(1).
doi:
10.1111/sji.13425.
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Allergen-specific immunoglobulin-E (As-IgE) in blood donors (BD) can be transferred to transfusion recipients via plasma-containing blood components (PCBC) and sensitize recipient's mast cells. These cells can activate upon allergen exposure and cause allergy. This study aimed to assess sensitization profiles against an array of allergens in BD to identify donors with As-IgE and explore if this IgE can lead to allergic symptoms in recipients. Furthermore IgE sensitization was characterized in donors of PCBC that were associated with allergic transfusion reactions (ATR) in recipients. Serum samples from 300 randomly selected BD (RSBD) and 40 BD selected following 26 ATRs in patients transfused with PCBC from these donors were collected. IgE sensitization was tested by a line-blot enzyme-immunoassay and an ELISA-based IgE multiplex assay. Thirty-eight per cent of the RSBD had IgE to one or several allergens. High IgE levels with a potential to transfer to recipients of PCBC were also detected in some BD. Investigation of 2/3 of the PCBC from sensitized RSBD revealed no reports of ATR in recipients. IgE testing of donors associated with an ATR showed sensitization in 65% of the cases. We conclude that IgE testing of BD can reveal sensitization to different allergens, even though persons with severe allergies are not accepted as BD. The sensitization frequency appears higher in BD of PCBC that led to an ATR compared to the RSBD. No reports on ATR were found for PCBC from sensitized RSBD. More studies are needed to address the role of IgE-sensitization of BD in ATR.
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Hetland, Geir; Fagerhol, Magne Kristoffer; Mirlashari, Mohammad Reza; Nissen-Meyer, Lise Sofie Haug; Croci, Stefania & Lonati, Paola Adele
[Show all 13 contributors for this article]
(2024).
Elevated NET, Calprotectin, and Neopterin Levels Discriminate between Disease Activity in COVID-19, as Evidenced by Need for Hospitalization among Patients in Northern Italy.
Biomedicines.
12:766(4),
p. 1–11.
doi:
10.3390/biomedicines12040766.
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Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful for discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining patients were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NETs), calprotectin, and DNase plasma levels via ELISA and a panel of proinflammatory cytokines via ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and do so more in hospitalized than non-hospitalized patients. C5a and sC5b-9, and other acute phase proteins, correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NETs, and neopterin are important proinflammatory parameters potentially useful for discriminating between COVID-19 patients at risk of hospitalization.
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Nguyen, Nhan Trung; Titze, Thomas Larsen & Nissen-Meyer, Lise Sofie Haug
(2024).
Evaluation of transfusion reactions in patients following transfusion of blood components containing antibodies to HLA class I – An attempt to prevent TRALI in patients.
Transfusion and Apheresis Science.
ISSN 1473-0502.
63(4).
doi:
10.1016/j.transci.2024.103970.
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Fagerhol, Magne Kristoffer; Schultz, Nina Haagenrud; Mirlashari, Mohammad Reza; Wiedmann, Markus; Nissen-Meyer, Lise Sofie Haug & Søraas, Arne Vasli Lund
[Show all 7 contributors for this article]
(2023).
DNase analysed by a novel competitive assay in patients with complications after ChAdOx1 nCoV-19 vaccination and in normal unvaccinated blood donors.
Scandinavian Journal of Immunology.
ISSN 0300-9475.
98(1).
doi:
10.1111/sji.13274.
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Abstract Increased levels of neutrophil extracellular traps (NETs) have been detected in individuals with vaccine complications after the ChAdOx1 nCov vaccine with a correlation between the severity of vaccine side effects and the level of NETosis. DNases may disrupt NETs by degrading their content of DNA, and a balance has been reported between NETs and DNases. Because of this and since the inflammatory marker NETs may be used as a confirmatory test in diagnosing VITT, it is of interest to monitor levels of DNase in patients with increased NETs levels. The current novel rapid DNase ELISA was tested in blood samples of patients with known increased levels of NETs with or without VITT after ChAdOx1 nCoV‐19 vaccination. DNase levels in VITT patients were significantly increased compared with normal unvaccinated blood donors and compared with patients with post‐vaccination symptoms but not VITT. However, since EDTA was found to inhibit DNase, serum and not EDTA‐plasma samples should be applied for DNase testing. The novel DNase assay may serve as a supplementary test to the NETs test when analysing samples from patients with suspected increased NETs levels.
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Johnsen, Katrine Neuman; Magnussen, Karin; Erstad, Christian; Bhatti, Sadaf Nabi & Nissen-Meyer, Lise Sofie Haug
(2023).
Safe Blood Donation from Donors Using Antihypertensive Medication. A Multi-Center Retrospective Quality Study from South-East Norway.
Journal of Blood Medicine.
14,
p. 337–343.
doi:
10.2147/JBM.S390609.
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Purpose: In Norway, blood donors using antihypertensive medication were deferred until 2015. Following revision of the national directive, these donors could be allowed, providing stable dose for at least 3 months, adequate blood pressure control and no adverse effects caused by the therapy. The new practice was evaluated by a quality study where the major aim was to establish whether donations from blood donors on antihypertensive medication pose a risk to the donor. The risk was assessed by counting the number and categorizing the adverse events related to blood donation. In addition, the quantitative effect of including these donors was calculated.
Subjects and methods: In this retrospective quality study, blood donors on antihypertensive therapy were recruited from four different blood centers to fill out a questionnaire. A total of 265 donors answered questions regarding their health status, type of medication used, and adverse events connected to blood donation both before and after starting the therapy.
Results: No severe adverse events were observed in donors on antihypertensive medications. The amount of mild adverse events, as exhibited by only 7 persons (0.46%) in this donor population, was the same as for donors without hypertensive treatment.
Conclusion: Blood donation from persons on antihypertensive therapy poses no extra risk of severe adverse events, given the use of screening criteria to identify and bleed only low-risk donors.
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Nissen-Meyer, Lise Sofie Haug; Macpherson, Magnhild Eide; Skeie, Linda Gail; Hvalryg, Marte; LLOHN, ABID HUSSAIN & Steinsvåg, Tine Torsvik
[Show all 17 contributors for this article]
(2023).
Covid-19-pasienter behandlet med rekonvalesensplasma.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
143(11).
doi:
10.4045/tidsskr.22.0577.
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BAKGRUNN I Norge er behandling med covid-19-rekonvalesensplasma gitt gjennom NORPLASMA-prosjektet. I begynnelsen ble behandlingen tilbudt kritisk syke pasienter etter individuell vurdering, men fra desember 2020 ble indikasjonen begrenset til kritisk syke pasienter med immunsvikt. Vi beskriver her kliniske karakteristika, komorbiditet og mortalitet hos pasienter som fikk rekonvalesensplasma i disse to periodene. MATERIALE OG METODE I perioden 22.4.2020–30.3.2022 ble 79 pasienter inkludert i observasjonsstudiene NORPLASMA MONITOR og Norwegian SARS-CoV-2-studien. Pasientene hadde mottatt totalt 193 enheter med rekonvalesensplasma ved 15 norske sykehus/sykehjem: 62 i Helse Sør-Øst, 8 i Helse Vest og 9 i Helse Midt-Norge. Opplysninger om immunstatus, komorbiditet og sykdomsforløp ble registrert fra pasientjournalen etter skriftlig samtykke. RESULTATER Av 79 pasienter med median alder 65 år (interkvartilbredde 51–73) som fikk behandling med rekonvalesensplasma, døde 31 (39 %) under sykehusoppholdet. 59 pasienter hadde immunsvikt, og blant disse døde 20 i sykehus, mot 11 av 20 antatt immunkompetente. Median antall komorbiditeter var 2 (interkvartilbredde 1–4). Pasientene fikk i median 2 plasmaenheter (min–maks 1–21). To av pasientene utviklet milde allergiske hudreaksjoner. FORTOLKNING Rekonvalesensplasma ble godt tolerert av pasienter med covid-19. Immunsviktpasienter hadde muligens effekt av behandlingen, med lavere dødelighet i denne gruppen enn blant antatt immunkompetente.
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Nissen-Meyer, Lise Sofie Haug; Steinsvåg, Christine Torsvik; Fenstad, Mona H.; Sørvoll, Ingvild Hausberg; Hvalryg, Marte & Titze, Thomas Larsen
[Show all 20 contributors for this article]
(2023).
Rekonvalesensplasma mot covid-19 fremstilt fra norske blodgivere.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
143(11),
p. 953–957.
doi:
10.4045/tidsskr.22.0180.
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BAKGRUNN I Norge er behandling med covid-19-rekonvalesensplasma gitt gjennom NORPLASMA-prosjektet. I begynnelsen ble behandlingen tilbudt kritisk syke pasienter etter individuell vurdering, men fra desember 2020 ble indikasjonen begrenset til kritisk syke pasienter med immunsvikt. Vi beskriver her kliniske karakteristika, komorbiditet og mortalitet hos pasienter som fikk rekonvalesensplasma i disse to periodene. MATERIALE OG METODE I perioden 22.4.2020–30.3.2022 ble 79 pasienter inkludert i observasjonsstudiene NORPLASMA MONITOR og Norwegian SARS-CoV-2-studien. Pasientene hadde mottatt totalt 193 enheter med rekonvalesensplasma ved 15 norske sykehus/sykehjem: 62 i Helse Sør-Øst, 8 i Helse Vest og 9 i Helse Midt-Norge. Opplysninger om immunstatus, komorbiditet og sykdomsforløp ble registrert fra pasientjournalen etter skriftlig samtykke.RESULTATER Av 79 pasienter med median alder 65 år (interkvartilbredde 51–73) som fikk behandling med rekonvalesensplasma, døde 31 (39 %) under sykehusoppholdet. 59 pasienter hadde immunsvikt, og blant disse døde 20 i sykehus, mot 11 av 20 antatt immunkompetente. Median antall komorbiditeter var 2 (interkvartilbredde 1–4). Pasientene fikk i median 2 plasmaenheter (min–maks 1–21). To av pasientene utviklet milde allergiske hudreaksjoner. FORTOLKNING Rekonvalesensplasma ble godt tolerert av pasienter med covid-19. Immunsviktpasienter hadde muligens effekt av behandlingen, med lavere dødelighet i denne gruppen enn blant antatt immunkompetente.
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Mirlashari, Mohammad Reza; Vetlesen, Annette; Nissen-Meyer, Lise Sofie Haug & Hetland, Geir
(2023).
Effects of storage on quality and function of acid-treated platelets with reduced HLA Class I surface expression.
Transfusion Medicine.
ISSN 0958-7578.
33(4),
p. 329–336.
doi:
10.1111/tme.12983.
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Abstract Background Refractory patients need to be provided with HLA‐matched platelets (PLTs), which require time‐consuming cross‐matching. Treatment of PLTs with citric acid leads to denaturation of the HLA Class I complexes without significant damage to the PLTs. HLA Class I depleted PLTs could alternatively be used to HLA‐matched PLTs for transfusion. These PLTs have verified normal function up to 4–6 h after acid treatment. Materials and Methods Buffy coat (BC) PLT concentrates were depleted of HLA Class I complexes by incubation in citric acid. The days after acid‐treatment, surface expression of HLA Class I complexes, CD62P and CD63 were determined by flow cytometry, in addition to viability and mitochondrial membrane potential (MMP). Thromboelastography (TEG) tested PLT functionality. Results Expression of HLA Class I complexes was reduced by 70%–75% in acid‐treated PLTs compared to untreated PLTs from day 1 through day 7. Controls and acid‐treated PLTs showed insignificant loss of MMP stored for 4 days. Analysis of the residual PLT activation and viability showed no significant differences for 4 days of storage. However, the residual PLT activation potential and viability were significantly decreased in acid‐treated PLTs and control PLTs after 7 days of storage. Acid treatment caused a significant decrease in the TEG variable, reaction time (R time), for acid‐treated PLTs as compared to control PLTs from days 1 through day 3. Conclusion Our data suggest that extended storage of acid‐treated PLTs is possible and will improve flexibility when planning for transfusion of patients with alloimmune PLT refractoriness caused by anti‐HLA‐antibodies.
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Meyer, Saskia; Blaas, Isaac; Bollineni, Ravi Chand; Delic-Sarac, Marina; Tran, Trung & Knetter, Cathrine
[Show all 20 contributors for this article]
(2023).
Prevalent and immunodominant CD8 T cell epitopes are conserved in SARS-CoV-2 variants.
Cell reports.
42(1).
doi:
10.1016/j.celrep.2023.111995.
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The emergence of SARS-CoV-2 variants of concern (VOC) is driven by mutations that mediate escape from neutralizing antibodies. There is also evidence that mutations can cause loss of T cell epitopes. However, studies on viral escape from T cell immunity have been hampered by uncertain estimates of epitope prevalence. Here, we map and quantify CD8 T cell responses to SARS-CoV-2-specific minimal epitopes in blood drawn from April to June 2020 from 83 COVID-19 convalescents. Among 37 HLA ligands eluted from five prevalent alleles and an additional 86 predicted binders, we identify 29 epitopes with an immunoprevalence ranging from 3% to 100% among individuals expressing the relevant HLA allele. Mutations in VOC are reported in 10.3% of the epitopes, while 20.6% of the non-immunogenic peptides are mutated in VOC. The nine most prevalent epitopes are conserved in VOC. Thus, comprehensive mapping of epitope prevalence does not provide evidence that mutations in VOC are driven by escape of T cell immunity.
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Mahmood, Faiza; Nissen-Meyer, Lise Sofie Haug; Hetland, Geir & Nentwich, Ivo
(2023).
Assessing IgE sensitization profiles to birch and timothy grass pollen allergens in birch pollen allergic blood donors using an oligoplex specific IgE assay.
Scandinavian Journal of Clinical and Laboratory Investigation.
ISSN 0036-5513.
83(7),
p. 444–447.
doi:
10.1080/00365513.2023.2255972.
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IgE sensitization profiles to single birch allergens in birch-sensitized patients differ among European countries. The aim of this study was to determine the distribution of specific IgE antibodies to major and minor birch pollen allergens in a population of allergic Norwegian individuals by using a birch allergic blood donor population as a surrogate sample. Sixty blood donors were recruited and sampled based on birch allergy symptoms such as rhinitis, rhinoconjunctivitis and/or mild asthma in previous seasons. All sera were collected before start of the pollen season and tested using a line blot assay (Euroimmun AG, Lübeck, Germany) for IgE to birch and timothy pollen. Both extracts, single allergens, and cross-reacting carbohydrate determinants (CCD) were analysed. Only donors with specific IgE to birch and/or timothy grass were further evaluated. Specific IgE to birch pollen extract was found in 52 sera, and sensitization to timothy grass in 40 sera. Specific IgE to Bet v 1 was predominant in contrast to Bet v 4 which was absent. However, sensitization to the minor allergens Bet v 2 and 6 was always found together with high levels of IgE to Bet v 1. Subjects sensitized to the profilin Bet v 2 from birch were also sensitized to Phl p 12 from timothy grass. In conclusion, there was predominantly Bet v 1 sensitization in this cohort and low sensitization to minor allergens and cross-reactive allergens (Bet v 2, Bet v 4, Phl p 7 and Phl p 12).
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Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette
[Show all 40 contributors for this article]
(2022).
Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants.
npj Vaccines.
7(1).
doi:
10.1038/s41541-022-00586-7.
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Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.
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Hetland, Geir; Fagerhol, Magne Kristoffer; Dimova-Svetoslavova, Veselka Petrova; Mirlashari, Mohammad Reza; Nguyen, Nhan Trung & Lind, Andreas
[Show all 9 contributors for this article]
(2022).
Inflammatory markers calprotectin, NETs, syndecan-1 and neopterin in COVID-19 convalescent blood donors.
Scandinavian Journal of Clinical and Laboratory Investigation.
ISSN 0036-5513.
82(6),
p. 481–485.
doi:
10.1080/00365513.2022.2123387.
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Persisting inflammation has been discovered in lungs and other parenchymatous organs of some COVID-19 convalescents. Calprotectin, neutrophil extracellular traps (NETs), syndecan-1 and neopterin are general key inflammatory markers, and systemically enhanced levels of them may remain after the COVID-19 infection. These inflammatory markers were therefore measured in serum samples of 129 COVID-19 convalescent and 27 healthy blood donors or employees at Oslo Blood bank, Norway. Also antibodies against SARS-CoV-2 nucleocapsid antigen were measured, and timing of sampling and severity of infection noted. Whereas neopterin and NETs values remained low and those for syndecan-1 were not raised to statistically significant level, concentrations for calprotectin, as measured by a novel mixed monoclonal assay, were significantly increased in the convalescents. Antibodies against SARS-CoV-2 nucleocapsid antigen were elevated, but did not correlate with levels of inflammatory markers. Difference between the groups in only one biomarker makes evaluation of ongoing or residual inflammation in the convalescents difficult. If there is a low-grade inflammation, it would in that case involve neutrophils.
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Kared, Hassen; Wolf, Asia-Sophia Fumika Michaela; Alirezaylavasani, Amin; Ravussin, Anthony; Solum, Guri & Tran, Trung
[Show all 17 contributors for this article]
(2022).
Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults.
Nature Communications.
13(1).
doi:
10.1038/s41467-022-31888-y.
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Abstract The SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event have robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Individuals with Omicron SARS-CoV-2 breakthrough infections have significantly increased activated SARS-CoV-2 wild type Spike-specific cytotoxic T cells, activated follicular helper (T FH ) cells, functional T cell responses, boosted humoral responses, and rapid release of Spike and RBD-specific IgG + B cell plasmablasts and memory B cells into circulation. Omicron breakthrough infection affords significantly increased de novo memory T cell responses to non-Spike viral antigens. Concerted T and B cell responses may provide durable and broad immunity.
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Syversen, Silje Watterdal; Jyssum, Ingrid; Tveter, Anne Therese; Tran, Trung; Sexton, Joseph & Provan, Sella Aarrestad
[Show all 22 contributors for this article]
(2022).
Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy.
Arthritis & Rheumatology.
ISSN 2326-5191.
74(8),
p. 1321–1332.
doi:
10.1002/art.42153.
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Objective Immunogenicity and safety following receipt of the standard SARS–CoV-2 vaccination regimen in patients with immune-mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2-dose regimen and a third dose of SARS–CoV-2 vaccine in IMID patients receiving immunosuppressive therapy. Methods Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2-dose SARS–CoV-2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor-binding domain (RBD) of the SARS–CoV-2 spike protein were performed prior to and 2–4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor-binding domain of the full-length SARS–Cov-2 spike protein, were allotted a third vaccine dose. Results A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti-RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192–4,191) than in controls (median 3,355 AU/ml [IQR 896–7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA–1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable. Conclusion IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.
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Hetland, Geir; Fagerhol, Magne Kristoffer; Wiedmann, Markus; Søraas, Arne Vasli; Mirlashari, Mohammad Reza & Nissen-Meyer, Lise Sofie Haug
[Show all 9 contributors for this article]
(2022).
Elevated NETs and Calprotectin Levels after ChAdOx1 nCoV-19 Vaccination Correlate with the Severity of Side Effects.
Vaccines.
10(8).
doi:
10.3390/vaccines10081267.
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ChAdOx1 nCoV-19 vaccination has been associated with the rare side effect; vaccine-induced immune thrombotic thrombocytopenia (VITT). The mechanism of thrombosis in VITT is associated with high levels of neutrophil extracellular traps (NETs). The present study examines whether key markers for NETosis, such as H3-NETs and calprotectin, as well as syndecan-1 for endotheliopathy, can be used as prognostic factors to predict the severity of complications associated with ChAdOx1 vaccination. Five patients with VITT, 10 with prolonged symptoms and cutaneous hemorrhages but without VITT, and 15 with only brief and mild symptoms after the vaccination were examined. Levels of H3-NETs and calprotectin in the vaccinated individuals were markedly increased in VITT patients compared to vaccinees with milder vaccination-associated symptoms, and a strong correlation (r ≥ 0.745, p < 0.001) was found with severity of vaccination side effects. Syndecan-1 levels were also positively correlated (r = 0.590, p < 0.001) in vaccinees to side effects after ChAdOx1 nCoV-19 vaccination. We hypothesize that the inflammatory markers NETs and calprotectin may be used as confirmatory tests in diagnosing VITT.
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Nissen-Meyer, Lise Sofie Haug; Czapp, Elzbieta; Naper, Christian; Jensen, Tore & Boulland, Line
(2022).
Screening for antibodies to HLA class I in apheresis donors following Covid‐19 or SARS-CoV-2 vaccination.
Transfusion and Apheresis Science.
ISSN 1473-0502.
61(5).
doi:
10.1016/j.transci.2022.103567.
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Riise, Jon; Meyer, Saskia; Blaas, Isaac; Chopra, Adity; Tran, Trung & Delic-Sarac, Marina
[Show all 22 contributors for this article]
(2022).
Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination.
British Journal of Haematology.
ISSN 0007-1048.
197(6),
p. 697–708.
doi:
10.1111/bjh.18149.
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B-cell depletion induced by anti-cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, but effects on CD8 T-cell responses are unknown. Here, we investigated humoral and CD8 T-cell responses following two vaccinations in patients with lymphoma undergoing anti-CD20-mAb therapy as single agent or in combination with chemotherapy or other anti-neoplastic agents during the last 9 months prior to inclusion, and in healthy age-matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor-binding domain of the SARS-CoV-2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T-cell responses against prevalent human leucocyte antigen (HLA) class I SARS-CoV-2 epitopes were determined by peptide-HLA multimer analysis. Strong CD8 T-cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS-CoV-2-vaccinated, anti-CD20-treated patients with lymphoma, their CD8 T-cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B-cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID-19) vaccines, and development of vaccines aimed at eliciting T-cell responses to non-Spike epitopes might provide improved protection.
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Jyssum, Ingrid; Kared, Hassen; Tran, Trung; Tveter, Anne Therese; Provan, Sella Aarrestad & Sexton, Joseph
[Show all 22 contributors for this article]
(2021).
Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study.
The Lancet Rheumatology.
00.
doi:
10.1016/S2665-9913(21)00394-5.
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Background In rituximab-treated patients with rheumatoid arthritis, humoral and cellular immune responses after two or three doses of SARS-CoV-2 vaccines are not well characterised. We aimed to address this knowledge gap. Methods This prospective, cohort study (Nor-vaC) was done at two hospitals in Norway. For this sub-study, we enrolled patients with rheumatoid arthritis on rituximab treatment and healthy controls who received SARS-CoV-2 vaccines according to the Norwegian national vaccination programme. Patients with insufficient serological responses to two doses (antibody to the receptor-binding domain [RBD] of the SARS-CoV-2 spike protein concentration <100 arbitrary units [AU]/mL) were allotted a third vaccine dose. Antibodies to the RBD of the SARS-CoV-2 spike protein were measured in serum 2–4 weeks after the second and third doses. Vaccine-elicited T-cell responses were assessed in vitro using blood samples taken before and 7–10 days after the second dose and 3 weeks after the third dose from a subset of patients by stimulating cryopreserved peripheral blood mononuclear cells with spike protein peptides. The main outcomes were the proportions of participants with serological responses (anti-RBD antibody concentrations of ≥70 AU/mL) and T-cell responses to spike peptides following two and three doses of SARS-CoV-2 vaccines. The study is registered at ClinicalTrials.gov, NCT04798625, and is ongoing. Findings Between Feb 9, 2021, and May 27, 2021, 90 patients were enrolled, 87 of whom donated serum and were included in our analyses (69 [79·3%] women and 18 [20·7%] men). 1114 healthy controls were included (854 [76·7%] women and 260 [23·3%] men). 49 patients were allotted a third vaccine dose. 19 (21·8%) of 87 patients, compared with 1096 (98·4%) of 1114 healthy controls, had a serological response after two doses (p<0·0001). Time since last rituximab infusion (median 267 days [IQR 222–324] in responders vs 107 days [80–152] in non-responders) and vaccine type (mRNA-1273 vs BNT162b2) were significantly associated with serological response (adjusting for age and sex). After two doses, 10 (53%) of 19 patients had CD4+ T-cell responses and 14 (74%) had CD8+ T-cell responses. A third vaccine dose induced serological responses in eight (16·3%) of 49 patients, but induced CD4+ and CD8+ T-cell responses in all patients assessed (n=12), including responses to the SARS-CoV-2 delta variant (B.1.617.2). Adverse events were reported in 32 (48%) of 67 patients and in 191 (78%) of 244 healthy controls after two doses, with the frequency not increasing after the third dose. There were no serious adverse events or deaths. Interpretation This study provides important insight into the divergent humoral and cellular responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis. A third vaccine dose given 6–9 months after a rituximab infusion might not induce a serological response, but could be considered to boost the cellular immune response.
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Mirlashari, Mohammad Reza; Vetlesen, Annette; Nissen-Meyer, Lise Sofie Haug; Naper, Christian; Tjønnfjord, Geir Erland & Njerve, Ida Unhammer
[Show all 12 contributors for this article]
(2021).
HLA class I depletion by citric acid, and irradiation of
apheresis platelets for transfusion of refractory patients.
Transfusion.
ISSN 0041-1132.
61(4),
p. 1222–1234.
doi:
10.1111/trf.16282.
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Background Patients can form antibodies to foreign human leukocyte antigen (HLA) Class I antigens after exposure to allogeneic cells. These anti‐HLA class I antibodies can bind transfused platelets (PLTs) and mediate their destruction, thus leading to PLT refractoriness. Patients with PLT refractoriness need HLA‐matched PLTs, which require expensive HLA typing of donors, antibody analyses of patient sera and/or crossmatching. An alternative approach is to reduce PLT HLA Class I expression using a brief incubation in citric acid on ice at low pH. Methods and Materials Apheresis PLT concentrates were depleted of HLA Class I complexes by 5 minutes incubation in ice‐cold citric acid, at pH 3.0. Surface expression of HLA Class I complexes, CD62P, CD63, phosphatidylserine, and complement factor C3c was analyzed by flow cytometry. PLT functionality was tested by thromboelastography (TEG). Results Acid treatment reduced the expression of HLA Class I complexes by 71% and potential for C3c binding by 11.5‐fold compared to untreated PLTs. Acid‐treated PLTs were significantly more activated than untreated PLTs, but irrespective of this increase in steady‐state activation, CD62P and CD63 were strongly upregulated on both acid‐treated and untreated PLTs after stimulation with thrombin receptor agonist peptide. Acid treatment did not induce apoptosis over time. X‐ray irradiation did not significantly influence the expression of HLA Class I complexes, CD62P, CD63, and TEG variables on acid treated PLTs. Conclusion The relatively simple acid stripping method can be used with irradiated apheresis PLTs and may prevent transfusion‐associated HLA sensitization and overcome PLT refractoriness.
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Hvalryg, Marte & Nissen-Meyer, Lise Sofie H.
(2021).
Sero-prevalence of SARS-CoV-2 antibodies in blood donors during the third wave of infection in Norway, winter/spring 2021.
Transfusion and Apheresis Science.
ISSN 1473-0502.
p. 1–4.
doi:
10.1016/j.transci.2021.103256.
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Holm, Sverre; Kared, Hassen; Michelsen, Annika Elisabet; Kong, Xiang Yi; Dahl, Tuva Børresdatter & Schultz, Nina Haagenrud
[Show all 21 contributors for this article]
(2021).
Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia.
European Heart Journal.
ISSN 0195-668X.
42(39),
p. 4064–4072.
doi:
10.1093/eurheartj/ehab506.
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Aims - We recently reported five cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) 7–10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against corona virus disease 2019 (COVID-19). We aimed to investigate the pathogenic immunological responses operating in these patients.<p> <p>Methods and results - We assessed circulating inflammatory markers by immune assays and immune cell phenotyping by flow cytometry analyses and performed immunoprecipitation with anti-platelet factor (PF)4 antibody in plasma samples followed by mass spectrometry from all five patients. A thrombus was retrieved from the sinus sagittal superior of one patient and analysed by immunohistochemistry and flow cytometry. Precipitated immune complexes revealed multiple innate immune pathway triggers for platelet and leucocyte activation. Plasma contained increased levels of innate immune response cytokines and markers of systemic inflammation, extensive degranulation of neutrophils, and tissue and endothelial damage. Blood analyses showed activation of neutrophils and increased levels of circulating H3Cit, dsDNA, and myeloperoxidase–DNA complex. The thrombus had extensive infiltration of neutrophils, formation of neutrophil extracellular traps (NETs), and IgG deposits.<p> <p>Conclusions - The results show that anti-PF4/polyanion IgG-mediated thrombus formation in VITT patients is accompanied by a massive innate immune activation and particularly the fulminant activation of neutrophils including NETosis. These results provide novel data on the immune response in this rare adenoviral vector-induced VITT.
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Mirlashari, Mohammad Reza; Vetlesen, Annette; Nissen-Meyer, Lise Sofie Haug; Stensland, Maria Ekman; Singh, Sachin Kumar & Nyman, Tuula Anneli
[Show all 7 contributors for this article]
(2021).
Proteomic study of apheresis platelets made HLA class I deficient for transfusion of refractory patients.
PROTEOMICS - Clinical Applications.
ISSN 1862-8346.
15:e2100022(6),
p. 1–8.
doi:
10.1002/prca.202100022.
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Purpose Refractoriness can occur after repeated platelet (PLT) transfusions because of alloimmunization to HLA class I antigens on transfused PLTs and generation of anti-HLA antibodies that bind to the foreign PLTs and initiate their destruction. Such refractoriness can be overcome by provision of HLA-matched PLTs from HLA typed donors. However, since the procedure is both expensive and time-consuming, an alternative approach is to deplete PLTs of HLA class I molecules by a brief treatment with citric acid, on ice. This is shown to be feasible without damaging PLT function. We used label free quantitative mass spectrometry (MS)-based proteomics to investigate the effect of acid treatment on apheresis PLTs for combatting immunologic PLT refractoriness. Experimental Design Proteomic analyses are undertaken using PLTs from seven apheresis concentrates, which were split in two with or without acid treatment. Results In total 1717 proteins in apheresis PLTs were quantified using proteomics. Data are available via ProteomeXchange with identifier PXD027893 . Of these, the amount of 80 proteins changed significantly after acid treatment, but overall there were not any major differences in proteomes between samples with and without acid treatment. Conclusions and Clinical Relevance In general, the changes of PLT proteins after treatment with citric acid were quite small and functionally safe. Hence, this result taken together with our previously published data indicates that acid treated PLTs can be used for treatment of patients with PLT refractoriness and opens up for a clinical trial.
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Hetland, Geir; Tangen, Jon-Magnus; Mahmood, Faiza; Mirlashari, Mohammad Reza; Nissen-Meyer, Lise Sofie Haug & Nentwich, Ivo
[Show all 9 contributors for this article]
(2020).
Antitumor, Anti-inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifola frondosa: A Review of Preclinical and Clinical Studies.
Nutrients.
12(5),
p. 1–19.
doi:
10.3390/nu12051339.
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Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms’ anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions—tumor, inflammation and allergy—seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.
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Fagerhol, Magne Kristoffer; Johnson, Egil; Tangen, Jon-Magnus; Hollan, Ivana; Mirlashari, Mohammad Reza & Nissen-Meyer, Lise Sofie Haug
[Show all 7 contributors for this article]
(2020).
NETs Analyzed by Novel Calprotectin-Based Assays in Blood Donors, and Patients With Multiple Myeloma or Rheumatoid Arthritis. A Pilot Study.
Scandinavian Journal of Immunology.
ISSN 0300-9475.
91(5),
p. 1–5.
doi:
10.1111/sji.12870.
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Two novel enzyme-linked immunosorbent assays (ELISAs), designed to detect complexes containing DNA, leucocyte calprotectin and S100A12 proteins, were generated for improved specificity and rapid measurement of neutrophil extracellular traps (NETs). The assays were applied on plasma and serum samples from blood donors for establishment of reference values, and from patients with multiple myeloma (MM) or rheumatoid arthritis (RA) in order to examine putatively increased values in the two different inflammatory conditions. Although NETs were hardly detectable in healthy individuals, NET levels were as expected highly and statistically significantly increased in RA patients. The detection of statistically significantly increased NET levels in MM is a novel finding.
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Mahmood, Faiza; Hetland, Geir; Nentwich, Ivo; Mirlashari, Mohammad Reza; Ghiasvand, Reza & Nissen-Meyer, Lise Sofie Haug
(2019).
Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial.
Nutrients.
11(10),
p. 1–15.
doi:
10.3390/nu11102339.
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Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract AndosanTM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the AndosanTM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based AndosanTM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.
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Johnson, Egil; Therkelsen, Stig Palm; Nentwich, Ivo; Nissen-Meyer, Lise Sofie Haug & Hetland, Geir
(2019).
IgE-sensitization to food and inhalant allergens in IBD patients compared with normal blood donors at Oslo University Hospital, Norway.
Scandinavian Journal of Gastroenterology.
ISSN 0036-5521.
54(9),
p. 1107–1110.
doi:
10.1080/00365521.2019.1663445.
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Post, Joakim Iver; Leergaard, Trygve B.; Ratz, Veronika; Walaas, S. Ivar; Hörsten, Stephan von & Nissen-Meyer, Lise Sofie Haug
(2019).
Differential Levels and Phosphorylation of Type 1 Inositol 1,4,5-Trisphosphate Receptor in Four Different Murine Models of Huntington Disease.
Journal of Huntington's Disease.
ISSN 1879-6397.
8(3),
p. 271–289.
doi:
10.3233/JHD-180301.
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Nissen-Meyer, Lise Sofie Haug; Tjønnfjord, Geir Erland; Golebiowska, Elzbieta; Kjeldsen-Kragh, Jens & Akkøk, Cigdem Ahaein
(2015).
Paroksysmal nattlig hemoglobinuri ved Oslo universitetssykehus 2000-10 :.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
135(11),
p. 1039–1043.
doi:
10.4045/tidsskr.14.0444.
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Nissen-Meyer, Lise Sofie Haug & Chaudhry, Farrukh Abbas
(2013).
Protein kinase C phosphorylates the system N glutamine transporter SN1 (Slc38a3) and regulates its membrane trafficking and degradation.
Frontiers in Endocrinology.
4,
p. 1–7.
doi:
10.3389/fendo.2013.00138.
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The system N transporter SN1 (also known as SNAT3) is enriched on perisynaptic astroglial cell membranes. SN1 mediates electroneutral and bidirectional glutamine transport, and regulates the intracellular as well as the extracellular concentrations of glutamine. We hypothesize that SN1 participates in the glutamate/?-aminobutyric acid (GABA)-glutamine cycle and regulates the amount of glutamine supplied to the neurons for replenishment of the neurotransmitter pools of glutamate and GABA. We also hypothesize that its activity on the plasma membrane is regulated by protein kinase C (PKC)-mediated phosphorylation and that SN1 activity has an impact on synaptic plasticity. This review discusses reports on the regulation of SN1 by PKC and presents a consolidated model for regulation and degradation of SN1 and the subsequent functional implications. As SN1 function is likely also regulated by PKC-mediated phosphorylation in peripheral organs, the same mechanisms may, thus, have impact on e.g., pH regulation in the kidney, urea formation in the liver, and insulin secretion in the pancreas.
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Kvamme, Elling; Nissen-Meyer, Lise Sofie Haug; Roberg, Bjørg Åse & Torgner, Ingeborg Aasland
(2008).
Novel form of phosphate activated glutaminase in cultured astrocytes and human neuroblastoma cells, PAG in brain pathology and localization in the mitochondria.
Neurochemical Research.
ISSN 0364-3190.
33(7),
p. 1341–1345.
doi:
10.1007/s11064-008-9589-9.
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Nissen-Meyer, Lise Sofie Haug; Svalheim, S; Taubøll, Erik; Gjerstad, Leif; Reinholt, Finn P. & Jemtland, Rune
(2008).
How can antiepileptic drugs affect bone mass, structure and metabolism? Lessons from animal studies.
Seizure.
ISSN 1059-1311.
17.
doi:
10.1016/j.seizure.2007.11.024.
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Nissen-Meyer, Lise Sofie Haug; Svalheim, Sigrid; Taubøll, Erik; Reppe, Sjur; Lekva, Tove & Solberg, Lene Bergendal
[Show all 10 contributors for this article]
(2007).
Levetiracetam, phenytoin, and valproate act differently on rat bone mass, structure and metabolism.
Epilepsia.
ISSN 0013-9580.
48,
p. 1850–1860.
doi:
10.1111/j.1528-1167.2007.01176.x.
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Haug, Lise Sofie & Østvold, Anne Carine
(2000).
Regulation of type I IP3 receptors and neurodegeneration.
Current Topics in Biochemical Research.
ISSN 0972-4583.
2,
p. 77–89.
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Nissen-Meyer, Lise Sofie; Walaas, Sven Ivar & Østvold, Anne Carine
(2000).
Degradation of the Type I Inositol 1,4,5-Trisphosphate Receptor by Caspase-3 in SH-SY5Y Neuroblastoma Cells Undergoing Apoptosis.
Journal of Neurochemistry.
ISSN 0022-3042.
75(5),
p. 1852–1861.
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Nissen-Meyer, Lise Sofie; Jensen, Vidar; Hvalby, Øyvind Christian; Walaas, Sven Ivar & Østvold, Anne Carine
(1999).
Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic nucleotide-dependent kinases in vitro and in rat cerebellar slices in situ.
Journal of Biological Chemistry.
ISSN 0021-9258.
274(11),
p. 7467–7473.
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We have examined cyclic nucleotide-regulated phosphorylation of the neuronal type I inositol
1,4,5-trisphosphate (IP3) receptor immunopurified from rat cerebellar membranes in vitro and in rat cerebellar
slices in situ. The isolated IP3 receptor protein was phosphorylated by both cAMP- and cGMP-dependent
protein kinases on two distinct sites as determined by thermolytic phosphopeptide mapping, phosphopeptide
1, representing Ser-1589, and phosphopeptide 2, representing Ser-1756 in the rat protein (Ferris, C. D.,
Cameron, A. M., Bredt, D. S., Huganir, R. L., and Snyder, S. H. (1991) Biochem. Biophys. Res. Commun.
175, 192-198). Phosphopeptide maps show that cAMP-dependent protein kinase (PKA) labeled both sites with
the same time course and same stoichiometry, whereas cGMP-dependent protein kinase (PKG)
phosphorylated Ser-1756 with a higher velocity and a higher stoichiometry than Ser-1589. Synthetic
decapeptides corresponding to the two phosphorylation sites (peptide 1, AARRDSVLAA (Ser-1589), and
peptide 2, SGRRESLTSF (Ser-1756)) were used to determine kinetic constants for the phosphorylation by PKG
and PKA, and the catalytic efficiencies were in agreement with the results obtained by in vitro
phosphorylation of the intact protein. In cerebellar slices prelabeled with [32P]orthophosphate, activation of
endogenous kinases by incubation in the presence of cAMP/cGMP analogues and specific inhibitors of PKG
and PKA induced in both cases a 3-fold increase in phosphorylation of the IP3 receptor. Thermolytic
phosphopeptide mapping of in situ labeled IP3 receptor by PKA showed labeling on the same sites (Ser-1589
and Ser-1756) as in vitro. In contrast to the findings in vitro, PKG preferentially phosphorylated Ser-1589 in
situ. Because both PKG and the IP3 receptor are specifically enriched in cerebellar Purkinje cells, PKG may be
an important IP3 receptor regulator in vivo.
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Nissen-Meyer, Lise Sofie; Østvold, Anne Carine; Torgner, Ingeborg Aasland; Roberg, Bjørg Åse; Dvoráková, Lenka & Stastný, F.
[Show all 7 contributors for this article]
(1998).
Intracerebroventricular administration of quinolinic acid induces a selective decrease of inositol (1,4,5)-trisphosphate receptor in rat brain.
Neurochemistry International.
ISSN 0197-0186.
33,
p. 109–119.
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[3H]inositol(1,4,5)-trisphosphate (IP3) binding studies have shown
decreased [3H]IP3 binding to brain tissue in several neurodegenerative
diseases, including Alzheimer's and Huntington's diseases. In addition,
previous results obtained from brains of Alzheimer patients indicated a
reduction of IP3-receptor protein correlated to neuronal loss. The
neurotoxic effect of the glutamate receptor agonist quinolinic acid
(QUIN) was therefore examined with respect to the level of IP3-receptor
immunoreactivity in rat brain. Neuronal lesions were estimated with
antibodies to marker proteins for striatal medium-sized spiny neurons
(dopamine- and cyclic AMP-regulated phosphoprotein, Mr 32,000;
DARPP-32), synaptic vesicles(synaptophysin), mitochondria
(phosphate-activated glutaminase; PAG) and glial cells (glial
fibrillary acidic protein; GFAP). Injection of QUIN into rat
neostriatum induced a massive loss of striatal medium-sized spiny
neurons, and led to a comparable loss of IP3-receptor and PAG
immunoreactivity, suggesting a neuronal localisation of both these
proteins. In an effort to induce less pronounced excitotoxic damage,
intracerebroventricular infusion of QUIN was performed. Following this
lesion, the neostriatum showed a negligible loss of DARPP-32
immunoreactivity (-11+/-5%), but contained only 43+/-3% of IP3-receptor
immunoreactivity levels compared to controls. In the hippocampus,
cerebellum and entorhinal cortex, the IP3-receptor loss was less
pronounced. The decrease in the level of IP3-receptor immunoreactivity
appears to be selective with respect to the other proteins studied, and
the IP3-receptor thus shows extreme sensitivity to QUIN neurotoxicity
in the neostriatum.
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Nissen-Meyer, Lise Sofie; Østvold, Anne Carine; Cowburn, Richard F.; Garlind, Anita; Winblad, Bengt & Bogdanovich, Nenad
[Show all 7 contributors for this article]
(1996).
Decreased Inositol (1,4,5)-Trisphosphate Receptor Levels in Alzheimer's Disease Cerebral Cortex: Selectivety of Changes and Possible Correlation of Pathological Severity.
Neurodegeneration.
ISSN 1055-8330.
5,
p. 169–176.
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Magnusson, Andres; Nissen-Meyer, Lise Sofie; Walaas, Sven Ivar & Østvold, Anne Carine
(1993).
Calcium-induced degradation of the Inositol (1,4,5)-trisphosphate receptor/Ca(2+)-channel.
FEBS Letters.
ISSN 0014-5793.
323(3),
p. 229–232.
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Ca(2+)-induced degradation of the neuronal inositol (1,4,5)-trisphosphate receptor, a protein which regulates
Ca(2+)-release from intracellular stores, has been examined. The IP3-receptor, immunopurified from rat cerebellum,
appeared to be an excellent substrate for purified Ca(2+)-activated neutral protease (calpain). Incubation of
membranes or immunopurified IP3-receptor with Ca2+ and cerebellar cytosol also resulted in degradation of the
receptor. Two main fragments with approximate molecular masses of 130 and 95 kDa were generated, both of
which appeared to derive from the carboxyterminal Ca(2+)-channel-containing part of the protein. These data
suggest that activation of the IP3-receptor, by causing increases in intracellular [Ca2+], might result in degradation
of the N-terminal, IP3-binding part of the receptor.
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Nissen-Meyer, Lise Sofie
(2025).
A place for plasmapheresis.
Transfusion and Apheresis Science.
ISSN 1473-0502.
64(5).
doi:
10.1016/j.transci.2025.104234.
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The increased need for source plasma in the production of plasma-derived medical products has received attention and elicited diverse actions in Europe lately. The discrepancy between production and utilization poses ethical as well as medical questions to be discussed in the international community. The contribution of non-remunerated voluntary donors should be encouraged, and several nations have addressed the problem in national plasma strategy documents. Independent of this, blood centers have increased their plasmapheresis activity in efforts to increase plasma donation and retain valuable donors, in parallel with decreased use of cellular blood products. In Oslo Blood Center we have encouraged our whole blood donors to also donate plasma, by which we keep them active and prepared for whole blood donation if an urgent situation rises. In this commentary I describe the change of mind set necessary to increase the number of plasmaphereses within the current frameworks.
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Haugen, Morten; Magnussen, Karin; Aarsland, Tonje Eiane; Nissen-Meyer, Lise Sofie Haug & Strand, Tor Arne
(2024).
The effect of donation frequency on donor health in blood donors donating plasma by plasmapheresis: study protocol for a randomized controlled trial.
Trials.
25.
doi:
10.1186/s13063-024-08035-7.
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Background: The demand for plasma products is growing, necessitating an increase in plasma collection by plasmapheresis. While the 20th edition of the European Guidelines permits plasma donors in Europe to donate with 96-h donation intervals, the potential short- and long-term consequences of high-frequency plasma donations on donor health remain unknown. This study aims to measure the effect of plasma donation frequency on plasma protein composition, including total serum protein (TSP) and immunoglobulin G (IgG), in Norwegian male blood donors. Methods: This randomized controlled trial (RCT) included 120 male blood donors who were randomized into two intervention groups and one control group: high-frequency plasma donors (HFPDs) who donated 650 mL of plasma 3 times every 2 weeks, whereas regular-frequency plasma donors (RFPDs) who donated 650 mL of plasma 1 time every 2 weeks. The control group consisted of whole blood donors. The primary outcomes are the concentrations of TSP and IgG. Discussion: The findings from this study may have implications for recommendations related to donor health and plasma donation frequencies and may contribute to supporting the strategic independence of plasma products in Norway and Europe without compromising donor health.
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Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette
[Show all 40 contributors for this article]
(2023).
Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants (npj Vaccines, (2022), 7, 1, (174), 10.1038/s41541-022-00586-7).
npj Vaccines.
8(1).
doi:
10.1038/s41541-023-00600-6.
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Holter, Jan Cato; Søraas, Arne Vasli Lund & Nissen-Meyer, Lise Sofie Haug
(2021).
OUS-forskere mener pandemiberedskapen var mangelfull og fraværende.
[Journal].
NRK.no.
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Melby, Kjetil K.; Nissen-Meyer, Lise Sofie Haug & Lundin, Knut Erik Aslaksen
(2019).
Helicobacter pylori in patients with coeliaci compared to healthy blood donors.
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Nissen-Meyer, Lise Sofie Haug & Chaudhry, Farrukh Abbas
(2017).
Corrigendum: Protein kinase C phosphorylates the system N glutamine transporter SN1 (Slc38a3) and regulates its Membrane trafficking and Degradation [Front Endocrinol, 4, (2013) (138)] doi: 10.3389/fendo.2013.00138.
Frontiers in Endocrinology.
8:190,
p. 1–2.
doi:
10.3389/fendo.2017.00190.
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Chaudhry, Farrukh Abbas; Nissen-Meyer, Lise Sofie Haug; Popescu, Mark-Christian; Bjørkmo, Mona; Gudbrandsen, Marius & Hamdani, El Hassan
(2013).
SN2 (Slc38a5) resembles SN1 (Slc38a3) in electroneutral transport but partly differ in functional roles.
Journal of Neurochemistry.
ISSN 0022-3042.
125,
p. 153–153.
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Nissen-Meyer, Lise Sofie Haug
(2012).
PKC-mediated regulation of the rat glial glutamine transporter SN1 and its membrane trafficking.
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Nissen-Meyer, Lise Sofie Haug; Svalheim, Sigrid; Taubøll, Erik; Reppe, Sjur; Lekva, Tove & Solberg, Lene B.
[Show all 10 contributors for this article]
(2006).
Differential effects of anti-epileptic drugs on bone health in rats. Dose-dependent impairment of biomechanical and microstructural properties of rat femur by levetiracetam.
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Nissen-Meyer, Lise Sofie Haug; Jemtland, Rune & Gautvik, Kaare M
(2005).
Redusert BMD hos voksne mus heterozygote for den PTH-regulerte transkripsjonsfaktoren Sox4 kan skyldes hemmet osteoblastutvikling.
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Nissen-Meyer, Lise Sofie Haug; Jemtland, Rune & Gautvik, Kaare M
(2005).
Reduced BMD in adult Sox4+/- mice is associated with suppressed osteoblast activity in culture.
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Paro, Rita; Nissen-Meyer, Lise Sofie Haug; Fortunati, Dario; Pedersen, Mona E; Reppe, Sjur & Gautvik, Vigdis Teig
[Show all 10 contributors for this article]
(2005).
Adult mice heterozygous for the transcription factor Sox4 exhibit reduced bone mineral density and suppressed osteoblast activity in culture.
Bone.
ISSN 8756-3282.
36,
p. S122–S122.
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Nissen-Meyer, Lise Sofie Haug; Gautvik, Vigdis Teig; Reppe, Sjur; Reinholt, Finn P.; Gautvik, Kaare M & Jemtland, Rune
(2004).
Reduced bone Mineral Density in Adult Heterozygous Sox4+/- Mice.
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Nissen-Meyer, Lise Sofie; Torgner, Ingeborg Aasland & Østvold, Anne Carine
(1999).
Characterization of the cell death process in SH-SY5Y human neuroblastoma cells induced by bilirubin.
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Haug, Lise Sofie; Dvoráková, Lenka; Walaas, Sven Ivar & Østvold, Anne Carine
(1998).
The inositol (1,4,5)-trisphosphate receptor/Ca2+ channel protein is selectively decreased in rat brains treated with quinolinic acid.
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Haug, Lise Sofie; Jensen, Vidar; Hvalby, Øyvind Christian; Walaas, Sven Ivar & Østvold, Anne Carine
(1998).
Stimulation of cyclic GMP-dependent protein kinase leads to phosphorylation of type I inositol trisphosphate-receptor in rat cerebellar slices.
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Haug, Lise Sofie; Østvold, Anne Carine & Walaas, Sven Ivar
(1997).
Regulation of the neuronal IP3-receptor: a possible correlation to Alzheimer's disease.
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Haug, Lise Sofie; Østvold, Anne Carine; Torgner, Ingeborg Aasland; Roberg, Bjørg Åse; Dvoráková, Lenka & Walaas, Sven Ivar
(1996).
Type I inositol (1,4,5)-trisphosphate receptor and phosphate-activated glutaminase are highly enriched in neurons as compared to glial cells in rat neostriatum.
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Haug, Lise Sofie; Cowburn, Richard F.; Walaas, Sven Ivar & Østvold, Anne Carine
(1995).
The Inositol (1,4,5)-trisphosphate receptor is selectively degraded in brain tissues from patients with Alzheimer's disease.
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Haug, Lise Sofie; Walaas, Sven Ivar & Østvold, Anne Carine
(1994).
Phosphorylation of purified IP3-receptor from rat cerebellum by cyclic GMP-dependent protein kinase.
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Nissen-Meyer, Lise Sofie; Østvold, Anne Carine & Walaas, Sven Ivar
(1993).
Calcium-induced degradation of the IP3-receptor/Ca(2+)-channel.
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Mar. 10, 2025 1:11 PM
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Apr. 8, 2025 12:35 PM
