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Vitiligo after alemtuzumab treatment: Secondary autoimmunity is not all about B cells

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...

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Detalles Bibliográficos
Autores principales: Ruck, Tobias, Pfeuffer, Steffen, Schulte-Mecklenbeck, Andreas, Gross, Catharina C., Lindner, Maren, Metze, Dieter, Ehrchen, Jan, Sondermann, Wiebke, Pul, Refik, Kleinschnitz, Christoph, Wiendl, Heinz, Meuth, Sven G., Klotz, Luisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329330/
https://www.ncbi.nlm.nih.gov/pubmed/30404783
http://dx.doi.org/10.1212/WNL.0000000000006648
Descripción
Sumario: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.