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| Item Type: | Article |
|---|---|
| Title: | PML risk stratification using anti-JCV antibody index and L-selectin |
| Creators Name: | Schwab, N., Schneider-Hohendorf, T., Pignolet, B., Spadaro, M., Görlich, D., Meinl, I., Windhagen, S., Tackenberg, B., Breuer, J., Cantó, E., Kümpfel, T., Hohlfeld, R., Siffrin, V., Luessi, F., Posevitz-Fejfár, A., Montalban, X., Meuth, S.G., Zipp, F., Gold, R., Du Pasquier, R.A., Kleinschnitz, C., Jacobi, A., Comabella, M., Bertolotto, A., 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 |
| ISSN: | 1352-4585 |
| Publisher: | Sage Publications |
| Volume: | 22 |
| Number: | 8 |
| Page Range: | 1048-1060 |
| Date: | July 2016 |
| Official Publication: | https://doi.org/10.1177/1352458515607651 |
| PubMed: | View item in PubMed |
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