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Schwab, Nicholas; Schneider-Hohendorf, Tilman; Pignolet, Béatrice; Spadaro, Michela; Görlich, Dennis; Meinl, Ingrid; Windhagen, Susanne; Tackenberg, Björn; Breuer, Johanna; Cantó, Ester; Kümpfel, Tania; Hohlfeld, Reinhard; Siffrin, Volker; Luessi, Felix; Posevitz-Fejfár, Anita; Montalban, Xavier; Meuth, Sven G.; Zipp, Frauke; Gold, Ralf; Du Pasquier, Renaud A.; Kleinschnitz, Christoph; Jacobi, Annett; Comabella, Manuel; Bertolotto, Antonio; Brassat, David; Wiendl, Heinz (2016): PML risk stratification using anti-JCV antibody index and L-selectin. In: Multiple Sclerosis Journal, Vol. 22, No. 8: pp. 1048-1060
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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.