Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammatory arthritis and extra-articular involvement. It is a chronic inflammatory disorder caused in many cases by the interaction between genes and environmental factors including tobacco, primarily involving synovial joints. The disease typically starts in small peripheral joints, is usually symmetric, and affects more women than men, with an incidence ratio of 2:1 to 3:1.
The immunopathogenesis of rheumatoid arthritis spans decades, beginning with the production of autoantibodies against post-translationally modified proteins (checkpoint 1). This early phase may last for years with asymptomatic autoimmunity and progressive immune system remodeling. Over time, tissue tolerance erodes, leading to joint inflammation.
Defining inflammatory cell states in RA joint and innate immunity’s role in the pathogenesis is crucial. Raychaudhuri and colleagues have leveraged several single-cell technologies to better understand this disease, identifying specific cell types and their activation status in RA.
Early arthritis and chronic arthritis phases are marked by distinct checkpoints: recognition of modified proteins and T cell metabolic reprogramming. Genetic polymorphisms contribute 30–60% of the risk for RA, with HLA-class II alleles, specifically HLA-DRB1 alleles containing a sequence stretch from position 71–74 of the β-chain, conferring the strongest risk.
As an immunological entity, RA begins years to decades earlier than its clinical manifestation, usually in the 6th decade of life. Persistent articular inflammation and joint damage are driven by proliferating synovial tissue fibroblasts as well as T and B lymphocytes.
To gain a deeper understanding of the immunology of rheumatoid arthritis, you can refer to these sources:
PubMed
Nature Immunology
PMC – National Center
NCBI Bookshelf
Nature PDF
Nature Immunology Review
PMC Article on RA
