# B cell receptor signaling in autoimmune rheumatic diseases: regulatory mechanisms and therapeutic targeting

## TL;DR

This paper reviews how B cell receptor signaling contributes to autoimmune rheumatic diseases and explores its role as a potential therapeutic target.

## Contribution

The paper integrates recent clinical and mechanistic insights to position BCR signaling as a central target in autoimmune rheumatic diseases.

## Key findings

- BCR signaling is a shared pathogenic axis in autoimmune rheumatic diseases.
- Targeting BCR signaling shows variable therapeutic responses across different diseases.
- Biomarker-guided strategies could improve treatment outcomes in these diseases.

## Abstract

Autoimmune rheumatic diseases (ARDs) are a diverse group of chronic disorders characterized by immune dysregulation and multi-organ inflammation. B cell receptor (BCR) signaling emerges as a shared, yet heterogeneously regulated, pathogenic axis across these diseases. This dysregulation drives B cell activation, autoantibody production, and ultimately tissue damage. Recent research highlights its involvement in both common and disease-specific mechanisms, which helps explain the wide variation in clinical features and therapeutic responses across ARDs. This review summarizes current evidence establishing BCR signaling as a central regulatory and therapeutic target in rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, IgG4-related disease, and ANCA-associated vasculitis. It integrates mechanistic insights with recent clinical trial data on BCR signaling-targeted therapies, discussing factors that may contribute to variability in therapeutic responses and treatment limitations. Finally, we outline current challenges and future directions for precision medicine in ARDs, with a focus on biomarker-guided strategies and innovative combination therapies to improve patient outcomes.