D-PENICILLAMINE-INDUCED AUTOANTIBODIES IN A MOUSE MODEL

Objective. We have previously shown that the administration of D-penic illamine (D-PEN) to patients with rheumatoid arthritis induces circula ting insulin autoantibodies (INSAAB). In order to gain further insight into such immune responses, we measured a battery of circulating auto antibodies in 4 strains of mice receiving D-PEN: C57BL/KsJ, BALB/c, C3 H/HeJ, and C57BL/6. These rodents groups differ in their degree of sus ceptibility to streptozotocin (STZ)-induced immune diabetes (SIMD), wh ich is high in the first 2 strains, and mild and nil in the third and fourth, respectively. Methods. Randomly assigned animals from each gro up were given a weekly subcutaneous (SC) injection of either D-PEN I m g, D-PEN 3 mg, or solvent (PBS)for a period of 4 weeks. Serum levels o f antibodies to insulin, single stranded DNA (ssDNA), thyroglobulin, a nd cardiolipin were measured weekly. Results. Only the C57BL/KsJ and C 3H/HeJ mice reacted to D-PEN administration. When compared to the pre- treated and solvent-treated mice, D-PEN I mg, and to a lesser degree D -PEN 3 mg, induced elevation of antibodies to insulin and to ssDNA in C57/KsJ mice (p < 0.001), while only ssDNA antibodies were detected in the C3H/HeJ mice (p < 0.0001 for D-PEN I mg; p < 0.05 for D-PEN 3 mg) . D-PEN had no effect on the level of antibodies to cardiolipin or to thyroglobulin in any of the mice. Conclusions. This study showed that D-PEN induces an antigen(s)-specific humoral response only in mice alr eady inherently prone to autoimmunity This model suggests that the act ivation of autoimmunity by environmental factors is probably facilitat ed by genetic background, and might partly explain the diversity of au toimmune manifestations in D-PEN-treated patients.