D-penicillamine-induced pancreatic islet autoantibody production is independent of the immunogenetic background: A lesson from patients with Wilson'sdisease

D-penicillamine (D-PA) was reported to induce various immunological abnorma lities including production of autoantibodies to insulin. These abnormaliti es were mainly described in patients with primary immunological disorders s uch as rheumatoid arthritis. In order to clarify whether D-PA-induced immun e disorders are restricted to patients genetically prone to develop autoimm une diseases or to a direct drug effect, we tested for the presence of vari ous autoantibodies and for molecular HLA typing in 17 patients with Wilson' s disease treated with this drug. In 2/17 patients, low-titer (10 JDFU) cir culating islet cell autoantibodies (ICA) were detected, while smother patie nt was positive for the presence of insulin autoantibodies. None of the ser a tested showed reactivity for glutamic acid decarboxylase or ICA512, Five of twelve patients were positive for anti-single-stranded DNA autoantibody, Molecular HLA typing of the autoantibody-positive subjects showed that the y carry HLA haplotypes not associated with insulin-dependent diabetes. The insulin response to intravenous glucose tolerance test in two patients with autoantibodies was found to be normal. A second blood testing of the autoa ntibody-positive patients 5 months following initial evaluation revealed co nversion to negativity in all three. Our results suggest that D-PA-induced autoantibodies in patients with Wilson's disease are independent of the imm unogenetic background characteristics Of diabetes. (C) 1998 Academic Press.