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

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

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.

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.

Conclusion

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.

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Abbreviations

WD:

Wilson disease

SLE:

Systemic lupus erythematosus

HCV:

Hepatitis C virus

ANA:

Antinuclear antibodies

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Acknowledgments

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

Compliance with the Ethics Guidelines

ᅟ

Conflict of interest

None.

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.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany

    Jessica Seessle, Daniel Nils Gotthardt, Mark Schäfer, Annina Gohdes, Jan Pfeiffenberger, Wolfgang Stremmel & Karl Heinz Weiss

  2. Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany

    Daniel Nils Gotthardt & Karl Heinz Weiss

  3. Department of Gastroenterology, University Hospital Vienna, Vienna, Austria

    Peter Ferenci

Authors
  1. Jessica Seessle
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  2. Daniel Nils Gotthardt
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  3. Mark Schäfer
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  4. Annina Gohdes
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  5. Jan Pfeiffenberger
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  6. Peter Ferenci
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  7. Wolfgang Stremmel
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  8. Karl Heinz Weiss
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Corresponding author

Correspondence to Karl Heinz Weiss.

Additional information

Communicated by: Ertan Mayatepek

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Supplemental Table 1

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Seessle, J., Gotthardt, D.N., Schäfer, M. et al. Concomitant immune-related events in Wilson disease: implications for monitoring chelator therapy. J Inherit Metab Dis 39, 125–130 (2016). https://doi.org/10.1007/s10545-015-9866-0

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  • DOI: https://doi.org/10.1007/s10545-015-9866-0

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