Análise dos diferentes subtipos de células B TFH e TFC como marcadores biológicos associados ao risco de progressão da esclerose múltipla

Abstract

Multiple sclerosis (MS) is an inflammatory and demyelinating autoimmune disease of the central nervous system (CNS) characterized by progressive damage to the myelin sheath in genetically susceptible individuals, affecting a socioeconomically productive age group. Most patients (>80%) progress to acute episodes of neurological disability followed by total or partial clinical remission, known as relapsing-remitting MS (RRMS), which, over time, will progress to the secondary progressive form (SPMS). Although there is no cure, the RRMS form can be controlled with the use of different drugs that target Th1 and Th17 cells. Unfortunately, the treatment failure rate is significant, and there are no therapeutic options for the SP form. The discovery of B cell aggregates adjacent to areas of neurodegeneration in patients with SPMS suggests the involvement of humoral immunity in the progression of the disease, and this phenomenon may also be related to severe forms of RRMS. However, efficient activation of B cells depends on their ability to interact with follicular CD4+ T cells (TFH). However, it has been described that follicular CD8+ T cells (TFC), in chronic inflammation, also assist in the process of B cell activation. In this sense, the frequency of different subtypes of these lymphocytes in peripheral blood mononuclear cell cultures from RRMS patients was determined through flow cytometry after stimulation for 4 h with PMA and ionomycin. Furthermore, plasma levels of CXCL13 and Nfl were quantified by ELISA. Clinical data were obtained from the medical record. Our results demonstrate that patients at high risk of progression present a preferential expansion of HLA-DR+IgD- memory B cells and more functional plasmablasts (CD138+) that express high levels of HLA-DR. Moreover, these cells were directly correlated with plasma levels of CXCL13 and NfL. In contrast, high frequency of different B cell subtypes associated with immune regulation (IgD+HLA-DR-) among low-risk patients was inversely correlated with NfL levels. Regarding follicular T cells, our study observed a positive and significant correlation between TFC17.1 and TFC17 cellular phenotypes with plasma CXCL13 levels and disease severity. Although preliminary, our findings suggest that monitoring the different subtypes of B cells and TFH and TFC lymphocytes could become a standard signature associated with the outcome of MS and response to therapy.