Projects & Grants

Intrathecal IgM synthesis as a possible prognostic factor in multiple sclerosis patients: correlations with clinical and laboratory tests
Project IdSGS03/LF/2020-2021
Main solverIng. MUDr. David Zeman, Ph.D.
Periodr1/2020 - 12/2021
ProviderSpecifický VŠ výzkum
AnotationMultiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS). Recently, the role of B lymphocytes is at the center of research of the MS immunopathogenesis. According to recent research, these cells are capable to recirculate between the peripheral and CNS compartments and, after homing in the CNS and differentiation into plasma cells, they are responsible for intrathecal antibody synthesis, in particular oligoclonal IgG and kappa free light chains. Local free lambda light chain synthesis can be detected in 60 to 70 % MS patients and isolated studies as well as our yet unpublished experience point towards possible association between free lambda light chains and worse disease prognosis. In a proportion of MS patients (20 to 70 % according to various studies) intrathecal oligoclonal IgM synthesis is present as well, with a predominant specificity to myelin lipids (phosphatidylcholine in particular). The presence of CSF oligoclonal IgM bands in MS patients is strongly associated with unfavourable prognosis in some studies, whereas no such association was found in others. CD19+ CD5+ B lymphocytes are elevated in CSF of MS patients and are presumably responsible for intrathecal oligoclonal IgM synthesis. More detailed phenotypic characteristics of these cells in MS has not been investigated. The composition of light chains kappa and lambda in oligoclonal IgM has not been systematically studied either. The aim of the project is to find out whether intrathecal IgM synthesis can be used as a biomarker of unfavourable prognosis in our population of MS patients; to investigate the composition of kappa and lambda light chains in intrathecally synthesised IgM bands; to verify the correlation between oligoclonal IgM positivity and increased amounts of CD19+ CD5+ B lymphocytes in the CSF; and to characterise in more detail this population in both CSF (in samples with enough B lymphocytes, i.e. >25/mL) and blood using flow cytometry.