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Anti-JCV antibody serology is associated with CSF cell counts in multiple sclerosis patients with and without natalizumab treatment
Author(s): ,
T. Schneider-Hohendorf
Affiliations:
Neurology, University of Muenster, Muenster
,
A. Schulte-Mecklenbeck
Affiliations:
Neurology, University of Muenster, Muenster
,
P. Ostkamp
Affiliations:
Neurology, University of Muenster, Muenster
,
F. Luessi
Affiliations:
Neurology, University of Mainz, Mainz, Germany
,
L. Klotz
Affiliations:
Neurology, University of Muenster, Muenster
,
F. Zipp
Affiliations:
Neurology, University of Mainz, Mainz, Germany
,
H. Wiendl
Affiliations:
Neurology, University of Muenster, Muenster
,
C.C. Gross
Affiliations:
Neurology, University of Muenster, Muenster
N. Schwab
Affiliations:
Neurology, University of Muenster, Muenster
ECTRIMS Online Library. Schneider-Hohendorf T. Oct 12, 2018; 228145
Tilman Schneider-Hohendorf
Tilman Schneider-Hohendorf
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Abstract: P1767

Type: Poster Sessions

Abstract Category: N/A

Background: Treatment of RRMS patients with natalizumab can be associated with the development of PML. The primary risk stratification factor since 2010 has been the detection of antibodies against the etiologic JC virus. JCV serology has been updated in 2014 to include the titer levels of the antibodies (anti-JCV index). CSF cell counts and cellular composition were analyzed in order to address issues of immune response and defence regarding JCV infection.
Methods: From 2011 to 2018, CSF samples of 137 RRMS patients were analyzed by standardized 10-color flow cytometry during routine diagnostic procedures. Patients were grouped by anti-JCV antibody serology (status and -index, resulting in three groups: JCV-, JCV-low < 1.5 and JCV-high ≥1.5), and cell counts per mL of CSF were investigated using a generalized linear mixed model adjusted for age, sex and current use of corticosteroids.
Results: 1. Patients during relapse presented with slightly higher cell counts of CD4 T cells, CD8 T cells, and NK cells. 2. Natalizumab treatment strongly reduced all cell populations except monocytes. 3. Patients with JCV index values of ≥1.5 presented with higher CSF cell counts, especially of T- and B cells, compared to JCV-, or patients with JCV indices < 1.5. 4. Data from 4 natalizumab-associated PML patients at diagnosis suggest comparatively low cell counts in the CSF.
Conclusions: Our results suggest that JC activity - reflected by high anti-JCV index values and -PML risk - is usually associated with high CSF cell counts. This could mean that these cells are recruited into the CNS by high virus activity and the need to control it. However, future studies will have to replicate, whether patients who later developed PML might indeed present with comparatively low cell numbers, which would be consistent with the hypothesis of impaired immune surveillance in these patients.
Disclosure: TSH received travel support from Biogen and received research and travel support from Novartis Pharma.
ASM has nothing to disclose.
PO has nothing to disclose.
FL received travel grants from Teva Pharmaceutical.
LK: received compensation for serving on Scientific Advisory Boards for Genzyme and Novartis; received speaker honoraria and travel support from Novartis, Merck Sorono, Biogen, and Genzyme; and receives research support from Novartis and Biogen.
F.Z. has received research grants from Teva, Merck Serono, Novartis and Bayer as well as consultation funds from Teva, Merck Serono, Novartis, Bayer Healthcare, Biogen Germany, ONO, Genzyme, Sanofi-Aventis and Octapharma. Her travel compensation has been provided for by the aforementioned companies.
HW: received honoraria for acting as a member of Scientific Advisory Boards and steering committees 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. Hofmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Peervoice, Sanofi-Genzyme, Swiss Multiple Sclerosis Society, TEVA, and WebMD Global; he acted as a paid consultant for Abbvie, Actelion, Biogen, IGES, Novartis, Roche Pharma AG, Sanofi-Genzyme, and GlaxoSmithKline GmbH; received research support from 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, Novartis, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children's Foundation, Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme.
CG: received speaker honoraria and travel support for attending meetings from Genzyme, Novartis, and Bayer Healthcare.
NS: received travel support from Sanofi-Genzyme and Novartis.

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