Primarily involves joints but extraarticular involvement

5% in some Native American populations

5% in females over 65 years old
Pathogenesis still unclear but progress being made

07/16/96

Understanding the pathology and specific inflammatory cells involved provides

rational basis for tx
RA is characterized by these pathologic findings:

07/16/96

Type A cells (macrophage like) >> Type B (fibroblast-like)

Type A cells recruited from bone marrow
Subsynovium: mononuclear cell inflitrate
Dendritic cells professional antigen presenting cells
Plasma cells polyclonal Ig production and IgM RFs
RF=Ab to Fc portion of other Igs
Angiogenesis

Th-2 = antiinflammatory profile

07/16/96

Tissue inhibitors of MMPs (TIMPs)

07/16/96

07/16/96

Build figure while describing main points as follows:

Autoimmune (T cell, APC, B cell, Plasma cell, IL-4, IL-6, IL-10 etc.)
Autoantibody production precedes joint inflammation
Genetic association with T cell antigen recognition,
mediated via ACPA
Inflammatory (Macrophage, Synoviocyte, Immune complexes, complement
fixation, IL6, TNF alpha, IL-1 etc.)
Migration of macrophages to synovium
Production of TNF/IL-6
Destructive (pannus, osteoclast, RANKL)

cricoarytenoid

07/16/96