title: D-penicillamine-induced pancreatic islet autoantibody production is independent of the immunogenetic background: a lesson from patients with Wilson's disease.
abstract: D-penicillamine (d-PA) was reported to induce various immunological abnormalities including production of autoantibodies to insulin. These abnormalities were mainly described in patients with primary immunological disorders such as rheumatoid arthritis. In order to clarify whether d-PA-induced immune disorders are restricted to patients genetically prone to develop autoimmune diseases or to a direct drug effect, we tested for the presence of various 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) circulating islet cell autoantibodies (ICA) were detected, while another patient was positive for the presence of insulin autoantibodies. None of the sera 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 they 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 autoantibody-positive patients 5 months following initial evaluation revealed conversion to negativity in all three. Our results suggest that d-PA-induced autoantibodies in patients with Wilson's disease are independent of the immunogenetic background characteristics of diabetes.
authors.affiliation: SCMCI, The Felsenstein Research Center, Petah Tiqva, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Kauschansky
authors.forename: M
authors.initials: M
authors.lastname: Frydman
authors.forename: S
authors.initials: S
authors.lastname: Assa
authors.forename: O J
authors.initials: OJ
authors.lastname: Kwon
authors.forename: S
authors.initials: S
authors.lastname: Israel
authors.forename: D
authors.initials: D
authors.lastname: Lazard
authors.forename: E
authors.initials: E
authors.lastname: Sprecher
authors.forename: K
authors.initials: K
authors.lastname: Bloch
authors.forename: C
authors.initials: C
authors.lastname: Brautbar
authors.forename: P
authors.initials: P
authors.lastname: Vardi
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006527:Hepatolenticular Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007125:Immunogenetics; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D010396:Penicillamine / Q000009:adverse effects*
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; C024211:islet cell antibody; D010396:Penicillamine