Response to b-cell depletion can be predicted

[frodo]

Autoantibodies against central nervous system antigens in a subset of B cell–dominant multiple sclerosis patients

https://www.pnas.org/content/early/2020 ... 9117.short

Significance

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). B cells play a key role in MS immunopathology, as demonstrated by the success of B cell-directed therapies; however, the target antigen of MS remains unknown.

Using a combination of ELISpot-based prescreening of peripheral blood mononuclear cells followed by investigation of antibody specificity with a CNS antigen array, we identified a population of MS patients characterized by a highly active B cell response.

These individuals with MS, who have active B cell responses, exhibited heterogeneous interindividual anti-CNS antibody responses, although the antigenic specificity of the antibodies remained stable over time for each individual.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), with characteristic inflammatory lesions and demyelination.

The clinical benefit of cell-depleting therapies targeting CD20 has emphasized the role of B cells and autoantibodies in MS pathogenesis. We previously introduced an enzyme-linked immunospot spot (ELISpot)-based assay to measure CNS antigen-specific B cells in the blood of MS patients and demonstrated its usefulness as a predictive biomarker for disease activity in measuring the successful outcome of disease-modifying therapies (DMTs).

Here we used a planar protein array to investigate CNS-reactive antibodies in the serum of MS patients as well as in B cell culture supernatants after polyclonal stimulation. Anti-CNS antibody reactivity was evident in the sera of the MS cohort, and the antibodies bound a heterogeneous set of molecules, including myelin, axonal cytoskeleton, and ion channel antigens, in individual patients. Immunoglobulin reactivity in supernatants of stimulated B cells was directed against a broad range of CNS antigens. A group of MS patients with a highly active B cell component was identified by the ELISpot assay. Those antibody reactivities remained stable over time.

These assays with protein arrays identify MS patients with a highly active B cell population with antibodies directed against a swathe of CNS proteins.