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December 11, 2018; 91 (24) ArticleOpen Access

Vitiligo after alemtuzumab treatment

Secondary autoimmunity is not all about B cells

Tobias Ruck, Steffen Pfeuffer, Andreas Schulte-Mecklenbeck, Catharina C. Gross, Maren Lindner, Dieter Metze, Jan Ehrchen, Wiebke Sondermann, Refik Pul, Christoph Kleinschnitz, Heinz Wiendl, Sven G. Meuth, Luisa Klotz
First published November 7, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006648
Tobias Ruck
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Steffen Pfeuffer
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Andreas Schulte-Mecklenbeck
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Catharina C. Gross
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Maren Lindner
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Dieter Metze
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Jan Ehrchen
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Wiebke Sondermann
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Refik Pul
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Christoph Kleinschnitz
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Heinz Wiendl
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Sven G. Meuth
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Luisa Klotz
From the Clinic of Neurology with Institute of Translational Neurology (T.R., S.P., A.S.-M., C.C.G., M.L., H.W., S.G.M., L.K.) and Department of Dermatology (D.M., J.E.), University of Münster; and Departments of Dermatology, Venereology, and Allergology (W.S.) and Neurology (R.P., C.K.), University School of Medicine Essen-Duisburg, Essen, Germany.
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Citation
Vitiligo after alemtuzumab treatment
Secondary autoimmunity is not all about B cells
Tobias Ruck, Steffen Pfeuffer, Andreas Schulte-Mecklenbeck, Catharina C. Gross, Maren Lindner, Dieter Metze, Jan Ehrchen, Wiebke Sondermann, Refik Pul, Christoph Kleinschnitz, Heinz Wiendl, Sven G. Meuth, Luisa Klotz
Neurology Dec 2018, 91 (24) e2233-e2237; DOI: 10.1212/WNL.0000000000006648

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Abstract

Objective To report 3 patients with relapsing-remitting multiple sclerosis (RRMS) showing vitiligo after treatment with alemtuzumab.

Methods Retrospective case series including flow cytometric analyses and T-cell receptor (TCR) sequencing of peripheral blood mononuclear cells.

Results We describe 3 cases of alemtuzumab-treated patients with RRMS developing vitiligo 52, 18, and 14 months after alemtuzumab initiation. Histopathology shows loss of epidermal pigmentation with absence of melanocytes and interface dermatitis with CD8+ T-cell infiltration. Also compatible with pathophysiologic concepts of vitiligo, peripheral blood mononuclear cells of one patient showed high proportions of CD8+ T cells with an activated (human leukocyte antigen–DR+), memory (CD45RO+), and type 1 cytokine (interferon-γ + tumor necrosis factor–α) phenotype at vitiligo onset compared to a control cohort of alemtuzumab-treated patients with RRMS (n = 30). Of note, analysis of CD8 TCR repertoire in this patient revealed a highly increased clonality and reduced repertoire diversity compared to healthy controls and treatment-naive patients with RRMS. We observed a predominance of single clones at baseline in this patient and alemtuzumab treatment did not substantially affect the proportions of most abundant clones over time.

Conclusion The 3 cases represent a detailed description of vitiligo as a T-cell-mediated secondary autoimmune disease following alemtuzumab treatment. The prevailing concept of unleashed B-cell responses might therefore not cover all facets of alemtuzumab-related secondary autoimmunity. Mechanistic studies, especially on TCR repertoire, might help clarify the underlying mechanisms.

Glossary

EDSS=
Expanded Disability Status Scale;
HLA=
human leukocyte antigen;
IFN-γ=
interferon-γ;
IL=
interleukin;
PBMC=
peripheral blood mononuclear cell;
RRMS=
relapsing-remitting multiple sclerosis;
TCR=
T-cell receptor;
TNF-α=
tumor necrosis factor–α

Footnotes

  • ↵* These authors contributed equally to this work.

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by the University of Münster.

  • Received May 9, 2018.
  • Accepted in final form August 28, 2018.
  • Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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