The research group focuses on the study of intrathecal immune responses in neurological diseases, in particular multiple sclerosis (MS). Through this, we aim to understand disease mechanisms to contribute to more specific therapeutic approaches.
The group is located at the Department of Molecular Medicine at the Institute of Basic Medical Sciences at the University of Oslo and at Dept. of Neurology, Akershus university hospital, where we collaborate closely with the research group of Trygve Holmøy. We employ a wide variety of techniques to map the cellular and humoral immune response in the CSF, such as high-throughput sequencing, single-cell RNA-seq, flow cytometry, isoelectric focusing, immunoblotting, T cell cloning, and mass spectrometry. We have postulated that the immune response in MS is initiated by viruses, such as Epstein Barr virus (EBV), and is driven by T cells and B cells within the central nervous system (CNS). These cells could recognize an exogenous antigen, an autoantigen, or immunogenic determinants, idiotopes (Id). To address these questions we study T cells and B cells from the cerebrospinal fluid (CSF) of MS-patients.
We have used high-throughput sequencing to chart the T cell and B cell repertoire in the CSF. This enabled us to characterize the compartmentalization of the B cell and T cell responses within the CSF in great detail. Moreover, we demonstrated that T cell receptors against EBV accumulate in the CSF of MS patients.
More recently, we have established single-cell RNA-seq of CSF mononuclear cells and combine this with mass spectrometry of CSF proteins.
- B cells and immunoglobulins in the cerebrospinal fluid of patients with MS
- Polymorphisms in human immungolublin heavy chain genes
- T follicular helper cells in MS
Lindeman I, Polak J, Qiao SW, Holmøy T, Høglund RA, Vartdal F, Berg-Hansen P, Sollid LM, Lossius A. Stereotyped B-cell responses are linked to IgG constant region polymorphisms in multiple sclerosis. European Journal of Immunology. 2022. https://doi.org/10.1002/eji.202149576
Høglund RA, Bremel RD, Homan EJ, Torsetnes SB, Lossius A*, Holmøy T*. CD4+ T Cells in the Blood of MS Patients Respond to Predicted Epitopes From B cell Receptors Found in Spinal Fluid. Frontiers in Immunology. 2020; 11: 598. *Shared senior authorship. https://doi.org/10.3389/fimmu.2020.00598
Tomescu-Baciu A, Johansen JN, Holmøy T, Greiff V, Stensland M, de Souza GA, Vartdal F, Lossius A. Persistence of intrathecal oligoclonal B cells and IgG in multiple sclerosis. Journal of Neuroimmunology. 2019; 333: 576966. https://doi.org/10.1016/j.jneuroim.2019.576966
Tomescu-Baciu A, Vartdal F, Holmøy T, Vedeler CA, Lossius A. G1m1 predominance of intrathecal virus-specific antibodies in multiple sclerosis. Annals of Clinical and Translational Neurology. 2018; 5(10): 1303-1309. https://doi.org/10.1002/acn3.642
Lossius A, Tomescu-Baciu A, Holmøy T, Vedeler CA, Røsjø E, Lorentzen ÅR, Casetta I, Vartdal F. Selective intrathecal enrichment of G1m1-positive B cells in multiple sclerosis. Annals of Clinical and Translational Neurology. 2017; 4(10):756-761. https://doi.org/10.1002/acn3.451