Contributions
Abstract: P1248
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab is an anti-CD52 antibody leading to rapid depletion followed by delayed repopulation of B and T lymphocytes and is approved for active relapsing-remitting multiple sclerosis (RRMS). Autoimmunity following alemtuzumab treatment represents the most relevant adverse event. Currently, it is assumed that B cells are the central drivers for these autoimmune conditions due to predominance of antibody-mediated autoimmune disorders.
Objectives/Aims: To report two 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 sequencing of peripheral blood mononuclear cells.
Results: Here, we describe two cases of alemtuzumab treated RRMS patients developing vitiligo 52 and 18 months after alemtuzumab initiation. Peripheral blood mononuclear cells of one patient were analyzed for vitiligo-related immune patterns. We found high proportions of CD8+ T cells with an activated (HLA-DR+), memory and type 1 cytokine (IFN-γ+ + TNF-α+) phenotype at vitiligo onset compared to a control cohort of alemtuzumab treated RRMS patients (n = 30). Of note, analysis of CD8 TCR (T cell receptor) repertoire in this patient revealed a highly increased clonality and reduced repertoire diversity compared to healthy controls and treatment-naïve RRMS patients. 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.
Conclusions: The two cases represent the first detailed description of vitiligo as 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 to understand the underlying mechanisms.
Disclosure: TR received travel expenses and financial research support from Genzyme and Novartis and received honoraria for lecturing from Roche, Merck, Genzyme, Biogen, and Teva.
SP received travel reimbursements and lecturing honoraria from Sanofi Genzyme and Biogen, Merck and Mylan. He received research support from Diamed.
ASM has nothing to disclose.
CCG received speaker honoraria and travel expenses for attending meetings from Biogen, Euroimmun, Genzyme, Novartis Pharma GmbH, and Bayer Health Care. Her work is funded by the German Ministry for Education and Research (BMBF; 01GI1603A), the German Research Foundation (DFG; GR3946/3-1 and SFB/Transregio 128 A09), and the European Union (Horizon2020, RESTORE).
ML has nothing to disclose.
DM has nothing to disclose.
JE received research grants from Pfizer and Actelion, was investigator for Boehringer Ingelheim and received speaker honoraria from Actelion, Pfizer and Chugai.
HW receives honoraria for acting as a member of Scientific Advisory Boards and as consultant for Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, as well as speaker honoraria and travel support from Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Global. HW is acting as a paid consultant for Abbvie, Actelion, Biogen, IGES, Novartis, Roche, Sanofi-Genzyme, and the Swiss Multiple Sclerosis Society. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children's Foundation, Biogen GmbH, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme.
SGM has received honoraria for lecturing, travel expenses for attending meetings and financial research support from Almirall, Bayer Health Care, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis and Teva.
L.K. received compensation for serving on Scientific Advisory Boards for Genzyme. She received speaker honoraria and travel support from Novartis, Merck Serono, and CSL Behring. She receives research support from Novartis.
Abstract: P1248
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Alemtuzumab is an anti-CD52 antibody leading to rapid depletion followed by delayed repopulation of B and T lymphocytes and is approved for active relapsing-remitting multiple sclerosis (RRMS). Autoimmunity following alemtuzumab treatment represents the most relevant adverse event. Currently, it is assumed that B cells are the central drivers for these autoimmune conditions due to predominance of antibody-mediated autoimmune disorders.
Objectives/Aims: To report two 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 sequencing of peripheral blood mononuclear cells.
Results: Here, we describe two cases of alemtuzumab treated RRMS patients developing vitiligo 52 and 18 months after alemtuzumab initiation. Peripheral blood mononuclear cells of one patient were analyzed for vitiligo-related immune patterns. We found high proportions of CD8+ T cells with an activated (HLA-DR+), memory and type 1 cytokine (IFN-γ+ + TNF-α+) phenotype at vitiligo onset compared to a control cohort of alemtuzumab treated RRMS patients (n = 30). Of note, analysis of CD8 TCR (T cell receptor) repertoire in this patient revealed a highly increased clonality and reduced repertoire diversity compared to healthy controls and treatment-naïve RRMS patients. 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.
Conclusions: The two cases represent the first detailed description of vitiligo as 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 to understand the underlying mechanisms.
Disclosure: TR received travel expenses and financial research support from Genzyme and Novartis and received honoraria for lecturing from Roche, Merck, Genzyme, Biogen, and Teva.
SP received travel reimbursements and lecturing honoraria from Sanofi Genzyme and Biogen, Merck and Mylan. He received research support from Diamed.
ASM has nothing to disclose.
CCG received speaker honoraria and travel expenses for attending meetings from Biogen, Euroimmun, Genzyme, Novartis Pharma GmbH, and Bayer Health Care. Her work is funded by the German Ministry for Education and Research (BMBF; 01GI1603A), the German Research Foundation (DFG; GR3946/3-1 and SFB/Transregio 128 A09), and the European Union (Horizon2020, RESTORE).
ML has nothing to disclose.
DM has nothing to disclose.
JE received research grants from Pfizer and Actelion, was investigator for Boehringer Ingelheim and received speaker honoraria from Actelion, Pfizer and Chugai.
HW receives honoraria for acting as a member of Scientific Advisory Boards and as consultant for Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, as well as speaker honoraria and travel support from Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Global. HW is acting as a paid consultant for Abbvie, Actelion, Biogen, IGES, Novartis, Roche, Sanofi-Genzyme, and the Swiss Multiple Sclerosis Society. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Else Kröner Fresenius Foundation, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children's Foundation, Biogen GmbH, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme.
SGM has received honoraria for lecturing, travel expenses for attending meetings and financial research support from Almirall, Bayer Health Care, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis and Teva.
L.K. received compensation for serving on Scientific Advisory Boards for Genzyme. She received speaker honoraria and travel support from Novartis, Merck Serono, and CSL Behring. She receives research support from Novartis.