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PML risk stratification using anti-JCV antibody index and L-selectin

Item Type:Article
Title:PML risk stratification using anti-JCV antibody index and L-selectin
Creators Name:Schwab, N. and Schneider-Hohendorf, T. and Pignolet, B. and Spadaro, M. and Görlich, D. and Meinl, I. and Windhagen, S. and Tackenberg, B. and Breuer, J. and Cantó, E. and Kümpfel, T. and Hohlfeld, R. and Siffrin, V. and Luessi, F. and Posevitz-Fejfár, A. and Montalban, X. and Meuth, S.G. and Zipp, F. and Gold, R. and Du Pasquier, R.A. and Kleinschnitz, C. and Jacobi, A. and Comabella, M. and Bertolotto, A. and Brassat, D. and Wiendl, H.
Abstract:Background: Natalizumab treatment is associated with progressive multifocal leukoencephalopathy (PML) development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for risk stratification, but PML incidence stays high. Anti-JCV antibody index and L-selectin (CD62L) have been proposed as additional risk stratification parameters. Objective: This study aimed at verifying and integrating both parameters into one algorithm for risk stratification. Methods: Multicentric, international cohorts of natalizumab-treated MS patients were assessed for JCV index (1921 control patients and nine pre-PML patients) and CD62L (1410 control patients and 17 pre-PML patients). Results: CD62L values correlate with JCV serostatus, as well as JCV index values. Low CD62L in natalizumab-treated patients was confirmed and validated as a biomarker for PML risk with the risk factor "CD62L low" increasing a patient's relative risk 55-fold (p < 0.0001). Validation efforts established 86% sensitivity/91% specificity for CD62L and 100% sensitivity/59% specificity for JCV index as predictors of PML. Using both parameters identified 1.9% of natalizumab-treated patients in the reference center as the risk group. Conclusions: Both JCV index and CD62L have merit for risk stratification and share a potential biological relationship with implications for general PML etiology. A risk algorithm incorporating both biomarkers could strongly reduce PML incidence.
Keywords:Natalizumab, PML, L-selectin, CD62L, JCV Index, Risk Stratification
Source:Multiple Sclerosis Journal
Publisher:Sage Publications
Page Range:1048-1060
Date:July 2016
Official Publication:https://doi.org/10.1177/1352458515607651
PubMed:View item in PubMed

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