Rheumatoid Arthritis and Inflammatory Disease

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by symmetric inflammatory polyarthritis targeting synovial joints. The pathogenesis begins with loss of immune tolerance to citrullinated self-antigens, leading to production of rheumatoid factor (RF — IgM antibody against the Fc portion of IgG) and anti-citrullinated protein antibodies (anti-CCP/ACPA) years before clinical disease onset (preclinical RA). The synovial membrane undergoes dramatic transformation: normally 1-2 cell layers thick, it proliferates into an invasive, tumor-like tissue called pannus. Pannus is composed of hyperplastic fibroblast-like synoviocytes (FLS), macrophages, T cells (CD4+ Th1 and Th17), B cells, and plasma cells. Pro-inflammatory cytokines — particularly TNF-alpha, IL-6, and IL-1 — drive synovial inflammation, angiogenesis, and cartilage/bone destruction. TNF-alpha activates osteoclasts via RANKL upregulation, causing juxta-articular bone erosions. IL-6 drives systemic inflammation (elevated CRP, ESR, anemia of chronic disease) and contributes to fatigue. The ACR/EULAR 2010 classification criteria assign points for joint involvement (small vs large joints, symmetric involvement), serology (RF, anti-CCP), acute phase reactants (CRP, ESR), and symptom duration (≥6 weeks), with a score ≥6/10 classifying as definite RA. The treat-to-target (T2T) strategy establishes remission...