Abstract
B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to brain antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that patients can be subdivided into responders that show brain-specific B cell reactivity in the blood and patients without this reactivity. Only in patients that classified as B cell responders, there was a significant positive correlation between treatment duration and the time since last relapse in our study. This correlation was GA-specific because it was absent in a control group that consisted of interferon-ß (IFN-β)-treated RRMS patients (n = 23). These data suggest that GA has an effect on brain-reactive B cells in a subset of patients and that only this subset benefits from treatment. The detection of brain-reactive B cells is likely to be a suitable tool to identify drug responders.
Highlights
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system (CNS) characterized by an initial inflammatory phase, followed by selective demyelination and neurodegeneration[1]
We separately examined Glatiramer acetate (GA) treatment duration, the brain-reactive B cell response and the time since last relapse with respect to the disability score of the patients
We hypothesized that the identification of brain-specific B cells in relapsing-remitting MS (RRMS) patients is as crucial at an early stage of the disease as the identification of treatment responders at the onset of GA therapy
Summary
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system (CNS) characterized by an initial inflammatory phase, followed by selective demyelination and neurodegeneration[1]. Studies of early active MS lesions reported interindividual heterogeneity, but intraindividual homogeneity in the patterns of demyelinating plaque pathology[3,4], where the most frequently observed pattern was selectively associated with immunoglobulin and complement deposition[3]. Contrasting this notion, it has been proposed that all MS lesions begin with oligodendrocyte apoptosis, followed by antibody deposition and complement activation[5]. The level of GA-specific antibodies of the TH2-associated IgG4 isotype was inversely correlated with the number of relapses, but only in long-term treatment[15]. Recent findings indicate that IFN-β increases the number of CD19+CD24++CD38++ transitional B cells, which in turn suppress the differentiation of CD4+ T cells[22,23]
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