Immunopathologic Role of Proteoglycan Antigens in Rheumatoid Joint Disease

Abstract

Cell-mediated immunity to proteoglycan antigens was assessed by leucocyte migration inhibition and by lymphocyte stimulation tests in patients with rheumatoid arthritis or with ankylosing spondylarthritis, in patients with relapsing synovitis after a single trauma to their knee joints, and in healthy donors. Both tests revealed a sensitization in most of the patients examined with various proteoglycan antigens derived from human cartilaginous tissues, rheumatoid synovial fluid, and species-common antigen of bovine nasal cartilage. Antibodies against proteoglycan antigens of human articular cartilage were detected by solid-phase radioimmunoassay in eleven out of twenty-nine sera from patients with rheumatoid arthritis and in four out of six rheumatoid synovial fluids. The results suggest that the cartilage antigenic components released by an inflammatory process or trauma may trigger a vicious circle of chronic inflammation and joint destruction.

Proteoglycan‐induced arthritis in balb/c mice

“…The immunity expresses itself through both the production of autoantibodies and the development of T cell-mediated cellular immunity. Whereas in rheumatoid arthritis, immunity is often directed against type I1 cartilage collagen (7,13,14)-particularly to its degraded form (2-5)-i n ankylosing spondylitis, immunity to cartilage proteoglycan has been detected more frequently (3,9).…”

Cartilage proteoglycan‐induced arthritis in BALB/c mice. Antibodies that recognize human and mouse cartilage proteoglycan and can cause depletion of cartilage proteoglycan with little or no synovitis

“…Proteoglycan (PG) and collagen, which are major structural components of the extracellular matrix of articular cartilage, have been implicated in autoimmune mechanisms leading to the development and/or persistence of inflammatory diseases in humans, such as rheumatoid arthritis, ankylosing spondylitis, and relapsing polychondritis (1)(2)(3)(4)(5)(6)(7). The injection of type I1 collagen from cartilage produces polyarthritis in genetically predisposed strains of rats (8,9) and mice (10).…”

Induction of arthritis in HLA–DR4–humanized and HLA–DQ8–humanized mice by human cartilage proteoglycan aggrecan but only in the presence of an appropriate (non‐MHC) genetic background

“…Fragments released during PG degradation may trigger and/or maintain local immune reactions in the synovial joints in arthritis-susceptible animals and perhaps in human individuals as well. Indeed, immune responses to human cartilage PG have been detected in patients with RA (28)(29)(30), supporting the hypothesis that, among other candidate autoantigens, cartilage PG might be a target of the autoimmune inflammatory attack in RA joint lesions.…”