Selective therapies are needed. Report about reation to B-cells treatment.

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Selective therapies are needed. Report about reation to B-cells treatment.

Post by frodo » Tue Apr 23, 2019 10:21 am

Selective treatments are needed. Some patients respond well to B-cells depletion while for others is contraindicated. ... 1.abstract

Immunological phenotyping identifies a subgroup of MS patients experiencing a proinflammatory immune cell activation upon therapeutic B cell removal


Objective: To study how anti-CD20 treatment of multiple sclerosis (MS) patients affects activation and cytokine production of myeloid antigen-presenting cells (APC) and T cells and whether a pre-existing regulatory B cell phenotype correlates with the extent of immune cell activation upon therapeutic B cell removal.

Background: In MS, B cell-depleting anti-CD20 antibodies efficiently reduce relapses and central nervous system lesion formation by abrogating APC function and pro-inflammatory cytokine secretion of B cells. However, B cells are moreover capable of regulating immune cells via anti-inflammatory cytokines, e.g. interleukin-10, a property which may be concomitantly eradicated by anti-CD20.

Design/Methods: To study the influence of B cells on other immune cells, we co-cultured murine macrophages, B and T cells in various settings. To investigate the effects of anti-CD20, we collected peripheral blood mononuclear cells of MS patients before and after treatment initiation and assessed phenotype and cytokine signature of B, T and myeloid cells by flow cytometry and ELISPOT.

Results: We identified a triangle of B, T and myeloid cells, in which B cell-derived interleukin-6 enhanced myeloid APC and T cell activation. Conversely, B cell-produced interleukin-10 regulated the APC-T cell axis in an anti-inflammatory manner. Reflecting these interactions, we identified distinct subgroups of MS patients with a pro-versus anti-inflammatory differentiation of monocytes and T cells after therapeutic removal of B cells.

Conclusions: The B cell-generated cytokine milieu is capable of shaping the activity of other immune cells. While in most MS patients, anti-CD20 treatment resulted in a desirable immunological outcome, others displayed an accentuated immune cell activation. We hypothesize that the latter situation reflects the loss of pre-existing B cell regulation, which we are currently evaluating. In context with clinical data, these investigations aim to generate immunological biomarkers to identify individual patients in whom B cells should not be unselectively eradicated.

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