BARCELONA—The anti-JCV antibody index and L-selectin (CD62L) have merit for risk stratification and share a potential biological relationship with implications for general progressive multifocal leukoencephalopathy (PML) etiology, according to research presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). “A risk algorithm incorporating both biomarkers could strongly reduce PML incidence,” said Nicholas Schwab, PhD, of the Department of Neurology at the University of Münster in Germany.
Natalizumab treatment is associated with PML development, with more than 541 cases as of March 3, 2015. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for categorical risk stratification, but PML incidence continues to rise steadily. Anti-JCV antibody index and CD62L have previously been proposed as additional risk stratification parameters. Dr. Schwab and his research colleagues aimed at verifying and integrating both parameters into one applicable algorithm for risk stratification.
The research team gathered international cohorts of patients with multiple sclerosis who were treated with natalizumab. The participants were assessed for JCV index (1,921 control patients and nine pre-PML patients) and CD62L (1,257 control patients and 17 pre-PML patients).
Low CD62L in natalizumab-treated patients was retrospectively confirmed and prospectively validated as a biomarker for PML risk. The risk factor “CD62L low” increased a patient’s relative risk 55-fold. Validation efforts established an 86% sensitivity and 91% specificity for CD62L and 100% sensitivity and 59% specificity for JCV index as predictors of PML.
Low CD62L values were also found in various other PML associations and stages (ie, lupus, lymphopenia, HIV, acute natalizumab-PML). CD62L values correlated with JCV serostatus, so the lower the CD62L value of a patient was, the higher the probability that they were JCV positive. The researchers ultimately found that 26 out of 27 (96%) patients with low CD62L were JCV positive. Additionally, CD62L values negatively correlated with JCV index values.
“The combined use of JCV serology and CD62L level found 2% of patients studied to be at highest risk,” Dr. Schwab reported. “Adherence to the risk-stratification algorithm might prevent up to or over 85% of PML cases,” he said.