The role of immune regulatory molecules in rheumatoid arthritis: Implication for etiopathogenesis and prospective for treatment

Abstract

Rheumatoid arthritis (RA) is considered an autoimmune chronic disorder and the most common inflammatory arthropathy. Disease progression in RA begins with asymptomatic autoimmune responses in cases with a genetic or environmental predisposition, that alters to arthralgia phase as autoantibodies reach the joints and subjects begin demonstrating nonspecific musculoskeletal presentations lacking any clinical symptoms of synovial inflammation. After that, patients' symptoms develop to undifferentiated arthritis (UA)/idiopathic arthritis (IA) whenever the subjects progress to clinical synovitis systemic comorbidities affecting the vasculature, metabolism, and bone, and eventually with augmented immune cell infiltration, IA/UA patients progress to clinically classifiable RA. RA is mainly correlated with different immune cells and each of them contributes variously to the pathogenesis of the disease. The pathogenesis of RA is altered by the contribution of both T and B cells in an autoimmune irregularity. Modulation of the immune responses occurs through regulatory and inhibitory molecules that control activation of the adaptive system as well as immune hemostasis. To confine the exorbitant T cell‐associated inflammatory reactions, the immune system provides a system of inhibitory feedbacks, collectively named immune checkpoints. In this review, we aimed to discuss about inhibitory members of immune checkpoint molecules, including programmed cell death 1 (PD‐1)/PD‐L1, cytotoxic‐T‐lymphocyte‐antigen‐4, lymphocyte activation gene‐3, T cell immunoglobulin‐3, V‐domain Ig suppressor of T cell activation, B‐ and T‐lymphocyte attenuator, and T cell immunoglobulin and ITIM domain and their role in RA.

Migraine and risk of rheumatoid arthritis: A systematic review and meta-analysis of observational studies

“…Rheumatoid arthritis (RA) is a chronic autoimmune joint disease whose pathophysiology is influenced by the involvement of T cells and B cells in autoimmune abnormalities [ 27 ]. Upon entering the body, RA-specific autoantigens activate an aberrant immune system mediated by several dendritic cell (DC) subtypes, T cells, macrophages, B cells, neutrophils, fibroblasts, and osteoclasts [ 28 ].…”

Osteomyelitis is associated with increased anti-inflammatory response and immune exhaustion

“…These molecules are important to keep the immune system in balance. Since the last decade, checkpoint molecules have been investigated in various malignancies (12) and autoimmune diseases as potential immunotherapy targets (13). Among the various candidates, programmed cell death protein 1 (PD-1), cytotoxic Tlymphocyte-associated protein 4 (CTLA-4), and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) are extensively studied checkpoint molecules in various diseases.…”