Induction of tolerance with intranasal administration of human cartilage gp-39 in DBA/1 mice - Amelioration of clinical, histologic, and radiologic signs of type II collagen-induced arthritis

Objective. Human cartilage glycoprotein 39 (HC gp-39) was recently identifi ed as a candidate autoantigen in the pathogenesis of rheumatoid arthritis, In the present studies, we investigated the capacity of HC gp-39 to interfe re in clinical disease induced by an unrelated autoantigen, type II collage n (CII), by the induction of cross-tolerance. Methods, DBA-1j/Bom mice were immunized with bovine CII/complete Freund's a djuvant and were given intraperitoneal booster injections of CII on day 21, Tolerance was induced via the intranasal pathway with either the disease-i nducing antigen (CII), a control antigen (ovalbumin), or HC gp-39 either be fore priming with CII or near the day of the booster injection. Arthritis w as monitored visually, and joint pathology was examined histologically and radiologically, In addition, CII antibody levels in serum were analyzed by enzyme-linked immunosorbent assay. Results. In contrast to treatment before priming, intranasal application of HC gp-39 after immunization markedly suppressed disease activity and preve nted joint destruction, whereas application of ovalbumin or CII was ineffec tive. Interference of HC gp-39 with the immune response to CII was demonstr ated by decreased anti-CII antibody levels. The combined data indicate that intranasal treatment with HC gp-39 may trigger modulatory or regulatory me chanisms that interfere with the expression of disease in murine collagen-i nduced arthritis, Conclusion. HC gp-39 is the first cross-tolerance-inducing protein in arthr itis that down-modulates a spectrum of disease features when given in a sem itherapeutic protocol.