The role of antibodies in mouse models of rheumatoid arthritis, and relevance to human disease.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting approximately 1% of the world’s population (Lee and Weinblatt, 2001). Although inflammatory lesions in the skin, lungs, and other organs are common, the disease hallmark is severe, often destructive, inflammation of peripheral joints. Although manifestations vary among patients, RA is usually a symmetric polyarthritis affecting distal [metacarpophalangeal (MCP), metatarsophalangeal (MTP), proximal interphalangeal (PIP), wrist, and ankle] more than intermediate (knee, elbow) and more than proximal (hip, shoulder) joints, and sparing the distal interphalangeal (DIP) joints. The cervical spine is often affected, but not the remainder of the axial skeleton. Synovial tendon sheaths and bursae are frequently involved. Microscopically, the characteristic lesion of RA is a novel tissue called pannus, composed of a greatly expanded number of both type 1 (macrophage-like) and type 2 (fibroblast-like) synoviocytes, as well as new blood vessels and a mononuclear cell infiltrate that is often follicular and can contain germinal centers. Although neutrophils are the predominant cell in inflamed synovial fluid, they are sparse in pannus. Pannus overgrows and erodes articular cartilage; destroys bone, especially at the junction of bone and cartilage; and erodes through tendons and ligaments. Together, these processes often destroy joint function, usually over the course of many years.