Journal of Inherited Metabolic Disease

, Volume 39, Issue 1, pp 125–130 | Cite as

Concomitant immune-related events in Wilson disease: implications for monitoring chelator therapy

  • Jessica Seessle
  • Daniel Nils Gotthardt
  • Mark Schäfer
  • Annina Gohdes
  • Jan Pfeiffenberger
  • Peter Ferenci
  • Wolfgang Stremmel
  • Karl Heinz Weiss
Original Article


Background and Aims

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.


We retrospectively analyzed 235 Wilson disease patients. Medical regimens were classified and analyzed in relation to adverse events and antinuclear antibody courses.


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.


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.


Systemic Lupus Erythematosus Autoimmune Thyroiditis Wilson Disease Menkes Disease Trientine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Wilson disease


Systemic lupus erythematosus


Hepatitis C virus


Antinuclear antibodies



We sincerely thank the patients for their help and willingness to participate in this study.

Compliance with the Ethics Guidelines

Conflict of interest


Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Supplementary material

10545_2015_9866_MOESM1_ESM.doc (40 kb)
Supplemental Table 1 (DOC 40 kb)
10545_2015_9866_MOESM2_ESM.doc (57 kb)
Supplemental Table 2 (DOC 57 kb)


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Copyright information

© SSIEM 2015

Authors and Affiliations

  • Jessica Seessle
    • 1
  • Daniel Nils Gotthardt
    • 1
    • 2
  • Mark Schäfer
    • 1
  • Annina Gohdes
    • 1
  • Jan Pfeiffenberger
    • 1
  • Peter Ferenci
    • 3
  • Wolfgang Stremmel
    • 1
  • Karl Heinz Weiss
    • 1
    • 2
  1. 1.Department of GastroenterologyUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Liver Cancer Center HeidelbergUniversity Hospital HeidelbergHeidelbergGermany
  3. 3.Department of GastroenterologyUniversity Hospital ViennaViennaAustria

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