Rheumatoid arthritis. From bench to bedside.

摘要: The clinical presentation of rheumatoid arthritis (RA) poses intriguing challenges to the elucidation underlying pathogenesis. Unifying hypotheses must explain onset and perpetuation inflammation, angiogenesis, hyperplasia within synovial membrane; articular destruction in cartilage bone compartments; propensity subsets patients manifest extra-articular involvement, variable prognosis, functional decline, mortality. This broad heterogeneity could alternatively instruct investigator that several disease processes coexist cohort defined by American College Rheumatology classification criteria. 3 During last decade, extraordinary advances have been made exploring pathogenetic events ongoing RA patients, culminating development application specific cytokine- cell-targeting agents with success. In parallel, radical alterations occurred use "traditional" disease-modifying antirheumatic drugs such most are now receiving combinations according regimens. 50 Such not, however, always derived from proven synergistic modes action. short review explores hypothesis translational science involving clinicians basic scientists common interests essential maintain further progress. A significant problem investigation pathogenesis human autoimmune diseases has absence reliable measures immune activity, reflecting, analogy, an "immunologic stethoscope." For many decades, associated autoantibody production, particularly through association factor expression. Autoimmune humoral responses may be identified detection autoantibodies serum; as such, they can related cohorts relative ease. Several novel specificities, including citrullinated peptides, Sa, RA33, (pro)filaggrin, patients. Some antibodies (e.g., anticitrullinated peptides anti-Sa) present early carry high specificity for RA, perhaps identifying clinically distinct subgroups. 21,57 Sensitivities remain low, these antibodies, presence multiple specificities individual is generally not rule. Much less known yet precise cellular contribute Investigation cell-mediated immunity logistic difficulties. Peripheral blood–derived leukocytes traditionally employed but likely represent than 2% total active cells. Critical immune-regulatory activities almost certainly occur lymph nodes target tissues, which difficult access. fact host tissues also directly responses, "nonprofessional immune" cells activated fibroblasts, epithelial cells) increasingly become evident emphasizes importance evaluating situ. absolute phenotype, tissue origin, kinetics developing elusive thus far. Formerly, studies relied exclusively on examination fluid or obtained at arthroplasty end-stage closed-needle biopsies. advent needle arthroscopy/direct vision biopsy contributing our understanding architecture membrane macro micro levels phases. 71 potential integrated pathway leading applied shown Figure 1. Well-characterized a prerequisite representative peripheral blood obtained. existence significance pathways interest then tested vitro vivo using animal model systems appropriate. Recent each stage this reviewed.