Alemtuzumab-induced changes in cerebrospinal fluid immune cell pattern - a prospective observational study
Author(s): ,
S. Pfeuffer
Affiliations:
Neurology Clinic and Institute for Translational Neurology, University of Muenster, Muenster, Germany
,
T. Ruck
Affiliations:
Neurology Clinic and Institute for Translational Neurology, University of Muenster, Muenster, Germany
,
L. Lammerding
Affiliations:
Neurology Clinic and Institute for Translational Neurology, University of Muenster, Muenster, Germany
,
A. Schulte-Mecklenbeck
Affiliations:
Neurology Clinic and Institute for Translational Neurology, University of Muenster, Muenster, Germany
,
C.C. Gross
Affiliations:
Neurology Clinic and Institute for Translational Neurology, University of Muenster, Muenster, Germany
,
H. Wiendl
Affiliations:
Neurology Clinic and Institute for Translational Neurology, University of Muenster, Muenster, Germany
,
L. Klotz
Affiliations:
Neurology Clinic and Institute for Translational Neurology, University of Muenster, Muenster, Germany
S.G. Meuth
Affiliations:
Neurology Clinic and Institute for Translational Neurology, University of Muenster, Muenster, Germany
ECTRIMS Online Library. Pfeuffer S. Oct 12, 2018; 229040; P1200
Dr. Steffen Pfeuffer
Dr. Steffen Pfeuffer
Contributions
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Abstract

Abstract: P1200

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

Objective: Alemtuzumab is a humanized monoclonal antibody that causes a rapid but long-lasting depletion of the CD52-bearing lymphoid lineage. Selective pulsed depletion is followed by a complex pattern of immune cell reconstitution that reflects the reshaping and potential reprogramming of immune networks, including the development of tolerance. Recent studies showed that pulsed-immune reconstitution therapy with alemtuzumab can produce durable efficacy after 2 courses of treatment (year 1 and 2). Thus far, the consequences of immune cell depletion for the immune cell composition in the cerebrospinal fluid (CSF) are unknown.
Methods: As part of the ALAIN study (“alemtuzumab in autoimmune inflammatory neurodegeneration”) and the PROGRAMMS cohort, we collected CSF samples from 21 patients immediately before and 12 months after the first course of alemtuzumab. Besides conventional CSF analysis, we conducted ten-color flow-cytometry of CSF cells to assess the cellular immune signature in the CSF and in comparison to peripheral blood.
Results: Total CSF cell counts as well as specific CSF lymphocyte populations are reduced 12 month after a first course of immune cell depletion. Specifically, a reduction of CD4+ T cells was observed, while CD8+ T cells and CD19+ B cells remained largely unaltered. The presence of CD138+ plasma cells in a proportion of MS patients was mostly unaffected. The reduction of CD4+ T cells was accompanied by elevated numbers of monocytes and NK cells in the CSF.
Conclusion: Taken together, our findings indicate that cellular immune cell composition following CD52- depletion is partially transferred from the peripheral blood to the CSF compartment. This process is unlikely to be directly caused by alemtuzumab-mediated depletion itself as the antibody should not cross the BBB in significant amounts. We assume that the reduction of CD4+ T cells is rather an “absence of replenishment” indicative of a vital crosstalk of immune cells beyond the BBB.
We aim for further follow-up to evaluate whether the observed changes are associated with either persistent NEDA status or rekindling disease activity. Additionally, we will add further analyses for examination of functional changes in immune cells as for example cytokine production.
This project is supported financially by Sanofi Genzyme and the Competence Network Multiple Sclerosis.
Disclosure: S. Pfeuffer: received speaker honoraria from Sanofi Genzyme, Biogen, Mylan Healthcare and travel reimbursements from Sanofi Genzyme, Biogen and Merck Serono.
T. Ruck: received travel expenses and financial research support from Genzyme and Novartis and received honoraria for lecturing from Roche, Merck, Genzyme, Biogen and Teva.
L. Lammerding: received travel reimbursements from Merck Serono and Sanofi-Genzyme.
A. Schulte-Mecklenbeck: declares no conflicts of interest.
C. Gross: received speaker honoraria and travel expenses for attending meetings from Genzyme, Novartis, and Bayer.
H. Wiendl: 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.
L. Klotz: received compensation for serving on scientific advisory boards from Genzyme and Novartis, speaker honoraria and travel support from CSL Behring, Merck Serono and Novartis) and research support from Biogen and Novartis.
S. Meuth: 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.

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