Role of B-Cell in the Pathogenesis of Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) is a rare multisystem autoimmune disease, characterized by fibrosis, vasculopathy, and autoimmunity. Recent advances have highlighted the significant implications of B-cells in SSc. B-cells are present in affected organs, their subpopulations are disrupted, and they display an activated phenotype, and the regulatory capacities of B-cells are impaired, as illustrated by the decrease in the IL-10+ producing B-cell subpopulation or the inhibitory membrane co-receptor density. Recent multi-omics evidence highlights the role of B-cells mainly in the early stage of SSc and preferentially during severe organ involvement. This dysregulated homeostasis partly explains the synthesis of anti-endothelial cell autoantibodies (AECAs) or anti-fibroblast autoantibodies (AFAs), proinflammatory or profibrotic cytokines (interleukin-6 and transforming growth factor-β) produced by B and plasma cells. That is associated with cell-to-cell interactions with endothelial cells, fibroblasts, vascular smooth muscle cells, and other immune cells, altogether leading to cell activation and proliferation, cell resistance to apoptosis, the impairment of regulatory mechanisms, and causing fibrosis of several organs encountered in the SSc. Finally, alongside these exploratory data, treatments targeting B-cells, through their depletion by cytotoxicity (anti-CD20 monoclonal antibody), or the cytokines produced by the B-cell, or their costimulation molecules, seem interesting, probably in certain profiles of early patients with severe organic damage.

Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis

“…Therefore, IL-10 can regulate the TLR4/NF-κB pathway in dermal fibroblasts through the IL-10 receptor (IL-10R)/STAT3 axis to reduce both ECM protein deposition and fibroblast transformation to myofibroblasts, thereby inhibiting the formation of skin scar induced by lipopolysaccharide. In addition, Thoreau et al ( 71 ) found that the expression of IL-10 was reduced in mouse models and patients with SSc and was associated with ILD formation. We found that the expression of COL1A1 in SSc plasma cirexos was negatively correlated with IL-10 in the SSc serum, which is consistent with the abovementioned studies.…”

Targeting B cells for treatment of systemic sclerosis

“…As a result, these immune cells further contribute to the inflammatory and fibrotic processes associated with SSc. Targeting B cells and their activity has become a therapeutic approach in SSc [7–9]. For example, rituximab, a monoclonal antibody that selectively depletes B cells, has been used in SSc patients with promising results [10,11,12 ▪ ,13–18].…”

Increased expression of the ectoenzyme CD38 in peripheral blood plasmablasts and plasma cells of patients with systemic sclerosis

“…A possible drawback for RTX efficacy may come from the fact that this drug is certainly efficacious in B cell depletion but plasma cells and hematopoietic stem cells are not among its targets. Long-lived plasma cells are thought to be an important player in SSc pathogenesis, as they infiltrate the skin of SSc patients together with CD20+ B cells and being the main source of SSc autoantibodies, that may also have a functional role ( 9 ).…”