Autoimmunity to collagen in adjuvant arthritis of rats.

Abstract

A B S T R A C T Arthritis can be induced in rats bv intradermal injection of oil containing bacterial derivatives (adjuvant-induced arthritis) or cartilage collagen (type II collagen-induced arthritis). It was of interest, therefore, to determine whether collagen functions as an autoantigen in rats with adjuvant arthritis. Blood mononuclear cells from the majority of rats with adjuvant arthritis exhibited enhanced thymidine incorporation to homologous types I and II collagens, as well as to purified protein derivative of tuberculin. In contrast, cells from rats remaining nonarthritic after injection of adjuvant did not respond to collagen, although they did react to tuberculin. Similar results were obtained with a radiometric ear assay used to quantifv intradermal delayed-type hypersensitivity in vivo. Using passive hemagglutination, autoantibodies to these collagens and their denatured a-chains were frequently detected in the sera of rats late in the course of adjuvant arthritis. Rats with inflammation of a hindlimb induced by turpentine did not acquire sensitivity to collagen. These data indicate that autoimmunity to collagen is a common feature of adjuvant-and collagen-induced arthritis, both of which are considered to be mediated by immunologic mechanisms.

Susceptibility to adjuvant arthritis in da and F344 RATS. A dominant trait controlled by an autosomal gene locus linked to the major histocompatibility complex

“…That adjuvant-induced arthritis may be identical to collagen-induced arthritis has been addressed by others (10,11,20). The 2 types of arthritis are phenotypically alike with similar strain distributions of susceptibility (20).…”

Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II.

“…Based on the finding of antibody or T lymphocyte responses to collagen type II in rats with AA (7) and in humans with rheumatoid arthritis (8), it has been suggested that collagen type II may be a critical self-antigen in autoimmune arthritis (7).…”

Clinical and Histological Assessment of Collagen-Induced Arthritis Progression in the Diabetes-Resistant BB/Wor Rat

“…Arthritis can be induced in susceptible strains of mice, rats, or nonhuman primates by immunization with heterologous native Type II collagen (CII) (2,3,18), mycobacteria-containing adjuvant [complete Freund's adjuvant CFA)] (14,17), or mycobacterial cell wall fragments suspended in mineral oil (14). These disease models share certain features with human RA, including clinical appearance of the arthritis, aspects of the histopathology including development of a proliferative synovitis, and MHC-linked genetic susceptibility (2,3,14,17,18). However, a detailed histological characterization of disease progression over time in these models has not been reported.…”