Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy

Abstract

Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients. Recently, disappearance of oligoclonal bands (OCB) from the CSF of a few natalizumab-treated patients with MS has been reported. This is interesting since CSF-restricted OCB are considered to persists in MS.Since lumbar punctures during natalizumab therapy are infrequent we pooled CSF data from fourteen MS centers to obtain a suitable patient cohort for furhter investigations about the suspected impact of natalizumab on CNS-restricted humoral immune activities.In a retrospective chart analysis CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy.

Novel serum autoantibodies against talin1 in multiple sclerosis: Possible pathogenetic roles of the antibodies

“…Interestingly, our clinical examination is similar to previous reports on OCB and IgG index of MS patients treated with natalizumab (Harrer et al, 2013;Mancuso et al, 2014;von Glehn et al, 2012). Natalizumab is an effective monoclonal antibody therapy for the treatment of relapsing-remitting MS patients that interferes with immune cell migration into the CNS by binding to VLA-4 (Polman et al, 2006), thus causing a pronounced and sustained reduction of immune cells in CSF (Stuve et al, 2006).…”

Effect of Multiple Sclerosis Disease-Modifying Therapies on B Cells and Humoral Immunity

“…Of interest, natalizumab decreases or eliminates CSF-restricted oligoclonal bands in 16% to 55% of patients. 38,39 This phenomenon has not been reported after other MS disease-modifying therapies. Natalizumab-treated patients are able to mount an immune response to vaccines, but this response may be attenuated compared with controls.…”

Intrathecal BCR transcriptome in multiple sclerosis versus other neuroinflammation: Equally diverse and compartmentalized, but more mutated, biased and overlapping with the proteome

“…Other observations do, however, point towards continuous recruitment of B cells from the periphery [40]. Thus, the main IgG-secreting cell type in CSF seems to be short-lived plasmablasts [7], founders of intrathecal B-cell clones have been detected in cervical lymph nodes [23], and intrathecal IgG synthesis is downregulated upon blocking the migration of immune cells by natalizumab [41]. Along with the sharing of clonally related B cells in CSF and blood reported by us and others [20][21][22], and the mutation pattern of IgG-secreting B cells shown herein, this supports that the intrathecal IgG synthesis in MS is part of an ongoing immune response on both sides of the blood-brain barrier.…”