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PML risk stratification using anti-JCV antibody index and L-selectin
Nicholas Schwab1, Tilman Schneider-Hohendorf2, Béatrice Pignolet3
1Department of Neurology, University of Münster, Germany nicholas.schwab@ukmuenster.de heinz.wiendl@ukmuenster.de.
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.
Insights
New biomarkers, the John Cunningham virus (JCV) index and L-selectin (CD62L), can improve risk stratification for progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients. Integrating these markers into an algorithm may significantly reduce PML incidence.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Clinical Risk Stratification
Background:
- Natalizumab treatment for multiple sclerosis (MS) is linked to progressive multifocal leukoencephalopathy (PML).
- Current risk stratification methods (treatment duration, prior immunosuppression, JCV serostatus) have limitations, as PML incidence remains high.
- The John Cunningham virus (JCV) antibody index and L-selectin (CD62L) are proposed as enhanced risk stratification parameters.
Purpose of the Study:
- To validate and integrate the JCV index and CD62L into a unified algorithm for PML risk stratification.
- To assess the predictive value of these biomarkers in natalizumab-treated MS patients.
Main Methods:
- Analysis of multicentric, international cohorts of natalizumab-treated MS patients.
- Assessment of JCV index in 1921 control and 9 pre-PML patients.
- Assessment of CD62L in 1410 control and 17 pre-PML patients.
Main Results:
- CD62L levels correlate with JCV serostatus and JCV index.
- Low CD62L was validated as a significant biomarker for PML risk, increasing relative risk 55-fold (p < 0.0001).
- CD62L demonstrated 86% sensitivity/91% specificity, and JCV index showed 100% sensitivity/59% specificity for predicting PML. A combined approach identified 1.9% of patients at high risk.
Conclusions:
- Both JCV index and CD62L are valuable for risk stratification and may share a biological link relevant to PML etiology.
- An integrated risk algorithm using both biomarkers holds potential to substantially decrease PML incidence.
- Further research into the biological relationship between CD62L, JCV index, and PML pathogenesis is warranted.
