Abstract General Information

Title

Increased production of anti-inflammatory molecules by a B cell subset of Multiple Sclerosis patients treated with Natalizumab

Abstract

Background and aim: Natalizumab (NTZ) is a widely used therapy for the relapsing-remitting forms of Multiple Sclerosis (RRMS). This humanized antibody blocks the α4 domain of the VLA4 integrin in leukocytes and prevents the migration of these cells to the Central Nervous System (CNS). The self-reactive lymphocytes that mediate the CNS inflammatory response remain in the periphery and apparently are regulated. Studies of regulatory T cells did not show an improved function in this population, but little is known about regulatory B cells' potential. Thus, we aim to evaluate the potential role of B cells in regulating the activated T cells from RRMS patients treated with NTZ.

Methods: Healthy donors (49) and RRMS patients receiving NTZ (37) consented to participate in the study (CAAE: 99798918.0.0000.5404). Peripheral blood mononuclear cells (PBMC) were isolated and labeled for analysis by flow cytometry (FACSymphony A5 BD). CD19+ cells were purified from PBMC to perform RT-PCR.

Results: The proportion of B cells (CD19+) was higher in NTZ-RRMS patients. The CD20+CD5+ B cell subset was reduced in the patients, however, these cells showed an increased anti-inflammatory profile, expressing the cytokines TGFbeta-1 and IL-27/IL-35. The expression of these molecules is one of the mechanisms by which B lymphocytes exert regulatory functions.

Conclusions: Our results suggest that NTZ treatment may induce a regulatory profile in the CD20+CD5+ B lymphocytes. These cells may contribute to maintaining homeostasis in the periphery during NTZ treatment. Further, we plan to co-culture those cells with self-reactive T lymphocytes to confirm their regulatory potential.

Financial support: FAPESP, CAPES, CNPq (INCT-NIM).
Keywords: regulatory B cells, anti-inflammatory cytokines, relapse remitting multiple sclerosis