Single-cell profiling reveals preferential reduction of memory B cell subsets in cladribine patients that correlates with treatment response.

"Declarations Ethics approval and consent to participate: Data and sample acquisition was performed at the Department of Neurology with Institute of Translational Neurology of the University Hospital Münster (approved by the local ethics committee Ärztekammer Westfalen-Lippe 2018-004557-24), the Institute for Clinical Neuroimmunology at the Ludwig-Maximilian-Universität München (Approval 163-16, specific project number 20-0996), and the Department of Neurology at the University Hospital Essen (20-9510-BO). All participants provided written informed consent prior to study entry, in accordance with the Declaration of Helsinki.Consent for publication: Not applicable.Author contributions:Valerie E. Teschner: Data curation; Formal analysis; Investigation; Methodology; Software; Visualization; Writing – original draft.Ann-Katrin Fleck: Formal analysis; Investigation; Methodology; Project administration; Software; Writing – review & editing.Carolin Walter: Data curation; Formal analysis; Software; Visualization; Writing – review & editing.Anna-Sophie Schwarze: Formal analysis; Investigation; Visualization; Writing – review & editing.Melanie Eschborn: Conceptualization; Funding acquisition; Investigation; Methodology; Writing – review & editing.Timo Wirth: Data curation; Formal analysis; Software; Visualization; Writing – review & editing.Olga V. Steinberg: Formal analysis; Visualization; Writing – review & editing.Andreas Schulte-Mecklenbeck: Writing – review & editing.I-Na Lu: Formal analysis; Writing – review & editing.Marisol Herrera-Rivero: Formal analysis; Software; Writing – review & editing.Claudia Janoschka: Investigation; Writing – review & editing.Jan D. Lünemann: Writing – review & editing.Nicholas Schwab: Writing – review & editing.Gerd Meyer zu Hörste: Writing – review & editing.Julian Varghese: Writing – review & editing.Catharina C. Gross: Writing – review & editing.Refik Pul: Resources; Writing – review & editing.Christoph Kleinschnitz: Resources; Writing – review & editing.Simone Mader: Writing – review & editing.Edgar Meinl: Resources; Writing – review & editing.Monika Stoll: Software; Writing – review & editing.Heinz Wiendl: Writing – review & editing.Luisa Klotz: Conceptualization; Funding acquisition; Investigation; Methodology; Project administration; Supervision; Writing – original draft; Writing – review & editing.Competing interests: VET was supported by the Medical Faculty of the University of Münster (Doctoral program ‘Medizinerkolleg MedK’). AKF received travel support from Novartis. ME received speaker honoraria and travel support from Sanofi-Genzyme. She received research support from the Deutsche Multiple Sklerose Gesellschaft (DMSG) Landesverband Nordrhein-Westfalen (NRW), the Innovative Medical Research (IMF) program of the University Münster, and Novartis. CJ received travel support from Novartis. JDL received speaker fees, research support, travel support, and/or served on advisory boards by Abbvie, Alexion, Adivo, Argenx, Biogen, Merck, Novartis, Roche, Sanofi, Takeda. NS reports grants from Biogen and Roche outside the submitted work. GMzH has received speaker honoraria and consultant/advisor reimbursement from Roche, LFB Pharma, and Alexion. CCG received speaker honoraria from DIU Dresden International University. She received research support from the European Union, the German Research Foundation, Biogen, and Roche. RP received honoraria for lecturing and consulting from Alexion, Bayer Healthcare, Biogen, Bristol-Mayers Squibb, MedDay, Merck Serono, Mylan, Novartis, Roche, and Sanofi Genzyme. He received research funds from Teva, Merck Serono, and Novartis. CK received remuneration for lectures and advisory boards from Alexion, Almirall, Bayer, Biogen, Boehringer Ingelheim, Bristol Myers-Squibb, Celgene, CSL Behring, Daiichi Sankyo, GE Healthcare, MedDay Pharmaceuticals, Merck Serono, Mylan/Viatris, Novartis, Pfizer, Roche, Sanofi-Genzyme, Stada, Teva, Biontech, Janssen-Cilag, Horizon Therapeutics GmbH, Medscape LLC, Baumgart Consultants GmbH; Shares from Biontech and Bayer. SM receives research support from Novartis. EM received honoraria or compensation from Bioeq, Novartis, Merck, Sanofi, and Teva. He received grant support from the DFG, Novartis, Roche, Merck, and GlycoEra. HW receives honoraria for acting as a member of Scientific Advisory Boards from Abbvie, Alexion, Argenx, Bristol Myers Squibb/Celgene, Janssen, Merck, Novartis, and Sandoz. Speaker honoraria and travel support from Alexion, Biogen, Bristol Myers Squibb, Genzyme, Merck, Neurodiem, Novartis, Ology, Roche, TEVA, and WebMD Global. HW is acting as a paid consultant for Abbvie, Actelion, Argenx, BD, Biogen, Bristol Myers Squibb, EMD Serono, Fondazione Cariplo, Gossamer Bio, Idorsia, Immunic, Immunovant, Janssen, Lundbeck, Merck, NexGen, Novartis, PSI CRO, Roche, Sanofi, Swiss Multiple Sclerosis Society, UCB, and Worldwide Clinical Trials. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Deutsche Myasthenie Gesellschaft e.V., Alexion, Amicus Therapeutics Inc., Argenx, Biogen, CSL Behring, F. Hoffmann – La Roche, Genzyme, Merck KgaA, Novartis, Roche Pharma, and UCB Biopharma. LK received compensation for serving on Scientific Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Genzyme, Horizon, Janssen, Merck Serono, Novartis, Roche, and Viatris. She received speaker honoraria and travel support from Bayer, Biogen, Bristol-Myers Squibb, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera, and Teva. She receives research support from the German Research Foundation, the IZKF Münster, IMF Münster, Biogen, Immunic AG, Novartis, and Merck Serono. CW, ASS, TW, OVS, ASM, INL, MHR, JV, and MS have nothing to disclose.Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the ‘Deutsche Forschungsgemeinschaft’ (DFG) SFB TR128 (project A08 to L.K.) and SFB1009 (project A03 to L.K.), as well as by the Interdisciplinary Center for Clinical Research (IZKF) Münster (K103/010/19 to L.K.). Parts of this study were funded by Merck Germany.Availability of data and materials: All data associated with this study are present in the article or the Supplemental Material. Data and codes of all scripts are available from the corresponding author on reasonable request. All models were created using publicly available packages and functions in the R programming language. Competing interests: VET was supported by the Medical Faculty of the University of Münster (Doctoral program ‘Medizinerkolleg MedK’). AKF received travel support from Novartis. ME received speaker honoraria and travel support from Sanofi-Genzyme. She received research support from the Deutsche Multiple Sklerose Gesellschaft (DMSG) Landesverband Nordrhein-Westfalen (NRW), the Innovative Medical Research (IMF) program of the University Münster, and Novartis. CJ received travel support from Novartis. JDL received speaker fees, research support, travel support, and/or served on advisory boards by Abbvie, Alexion, Adivo, Argenx, Biogen, Merck, Novartis, Roche, Sanofi, Takeda. NS reports grants from Biogen and Roche outside the submitted work. GMzH has received speaker honoraria and consultant/advisor reimbursement from Roche, LFB Pharma, and Alexion. CCG received speaker honoraria from DIU Dresden International University. She received research support from the European Union, the German Research Foundation, Biogen, and Roche. RP received honoraria for lecturing and consulting from Alexion, Bayer Healthcare, Biogen, Bristol-Mayers Squibb, MedDay, Merck Serono, Mylan, Novartis, Roche, and Sanofi Genzyme. He received research funds from Teva, Merck Serono, and Novartis. CK received remuneration for lectures and advisory boards from Alexion, Almirall, Bayer, Biogen, Boehringer Ingelheim, Bristol Myers-Squibb, Celgene, CSL Behring, Daiichi Sankyo, GE Healthcare, MedDay Pharmaceuticals, Merck Serono, Mylan/Viatris, Novartis, Pfizer, Roche, Sanofi-Genzyme, Stada, Teva, Biontech, Janssen-Cilag, Horizon Therapeutics GmbH, Medscape LLC, Baumgart Consultants GmbH; Shares from Biontech and Bayer. SM receives research support from Novartis. EM received honoraria or compensation from Bioeq, Novartis, Merck, Sanofi, and Teva. He received grant support from the DFG, Novartis, Roche, Merck, and GlycoEra. HW receives honoraria for acting as a member of Scientific Advisory Boards from Abbvie, Alexion, Argenx, Bristol Myers Squibb/Celgene, Janssen, Merck, Novartis, and Sandoz. Speaker honoraria and travel support from Alexion, Biogen, Bristol Myers Squibb, Genzyme, Merck, Neurodiem, Novartis, Ology, Roche, TEVA, and WebMD Global. HW is acting as a paid consultant for Abbvie, Actelion, Argenx, BD, Biogen, Bristol Myers Squibb, EMD Serono, Fondazione Cariplo, Gossamer Bio, Idorsia, Immunic, Immunovant, Janssen, Lundbeck, Merck, NexGen, Novartis, PSI CRO, Roche, Sanofi, Swiss Multiple Sclerosis Society, UCB, and Worldwide Clinical Trials. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Deutsche Myasthenie Gesellschaft e.V., Alexion, Amicus Therapeutics Inc., Argenx, Biogen, CSL Behring, F. Hoffmann – La Roche, Genzyme, Merck KgaA, Novartis, Roche Pharma, and UCB Biopharma. LK received compensation for serving on Scientific Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Genzyme, Horizon, Janssen, Merck Serono, Novartis, Roche, and Viatris. She received speaker honoraria and travel support from Bayer, Biogen, Bristol-Myers Squibb, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera, and Teva. She receives research support from the German Research Foundation, the IZKF Münster, IMF Münster, Biogen, Immunic AG, Novartis, and Merck Serono. CW, ASS, TW, OVS, ASM, INL, MHR, JV, and MS have nothing to disclose."

"Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the ‘Deutsche Forschungsgemeinschaft’ (DFG) SFB TR128 (project A08 to L.K.) and SFB1009 (project A03 to L.K.), as well as by the Interdisciplinary Center for Clinical Research (IZKF) Münster (K103/010/19 to L.K.). Parts of this study were funded by Merck Germany."