title: Concomitant immune-related events in Wilson disease: implications for monitoring chelator therapy.
abstract: OBJECTIVE
  Current guidelines favor the use of chelating agents (d-penicillamine, trientine) in first line therapy of symptomatic Wilson disease patients. Development of chelator induced immunological adverse events are a concern especially under d-penicillamine therapy. This study assessed the prevalence of co-existing or therapy-related immune-mediated diseases in Wilson disease patients, and evaluated the role of antinuclear antibodies in therapy monitoring.
  
  
  METHODS
  We retrospectively analyzed 235 Wilson disease patients. Medical regimens were classified and analyzed in relation to adverse events and antinuclear antibody courses.
  
  
  RESULTS
  Coexisting immune-mediated diseases were evident in 19/235 (8.1%) patients, of which 13/235 (5.5%) had pre-existing autoimmune diseases. Six patients (2.6%) developed an autoimmune disease under therapy, all of them under long-term d-penicillamine treatment. Data relating to antinuclear antibody courses during treatment and adverse events were available for patients treated with d-penicillamine (n = 91), trientine (n = 58), and zinc salts (n = 58). No significant increase in antinuclear antibody titers in patients treated with d-penicillamine (16/91; 17.6%), trientine (12/58; 20.7%), and zinc (7/58; 12.1%) were found.
  
  
  CONCLUSIONS
  Under long-term d-penicillamine therapy a minority of patients developed immune-mediated disease. Elevations in antinuclear antibodies were found frequently, but no correlations were evident between increases in antinuclear antibodies and the development of immune-mediated diseases or medical regimes. Thus, the value of antinuclear antibodies for monitoring adverse events under chelator therapy seems to be limited.
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Seessle
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany.|Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Daniel Nils
authors.initials: DN
authors.lastname: Gotthardt
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany.
authors.forename: Annina
authors.initials: A
authors.lastname: Gohdes
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Pfeiffenberger
authors.affiliation: Department of Gastroenterology, University Hospital Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany. karl-heinz_weiss@med.uni-heidelberg.de.|Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany. karl-heinz_weiss@med.uni-heidelberg.de.
authors.forename: Karl Heinz
authors.initials: KH
authors.lastname: Weiss
mesh_terms: D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology; D002614:Chelating Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D003430:Cross-Sectional Studies; D016903:Drug Monitoring / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000276:immunology*; D005260:Female; D006527:Hepatolenticular Degeneration / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D010396:Penicillamine / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D012189:Retrospective Studies; D014266:Trientine / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D055815:Young Adult; D015032:Zinc / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000974:Antibodies, Antinuclear; D002614:Chelating Agents; D010396:Penicillamine; D015032:Zinc; D014266:Trientine