Abstract Details

Title PML risk stratification using anti-JCV antibody index and L-selectin (CD62L)

Topic Multiple Sclerosis

Presentation(s) (-)

Poster/Presentation
Number 007

Objective

Background Natalizumab treatment is associated with PML development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for categorical risk stratification, but PML incidence stays high. Anti-JCV antibody index and L-selectin (CD62L) have been proposed as additional risk stratification parameters.

Design/Methods A multicentric cohort of natalizumab-treated MS patients was assessed for JCV index (2945 samples of 1864 patients) and CD62L (1307 samples of 510 patients; 3 pre-PML patients). Validation included additional 686 natalizumab-treated (non-PML) and 12 pre-PML patients in 6 independent cohorts from 4 different countries.

Results Natalizumab treatment increases JCV seroconversion at least eightfold and reduces CD62L levels. Low CD62L in natalizumab-treated patients was confirmed as a biomarker for PML risk with the risk factor “CD62L low” increasing a patient’s relative risk 37-fold (p<0.0001). JCV index and CD62L values show comparable longitudinal stability, both correlating with parameters of cellular viability: high cellular viability is, therefore, associated with low JCV index and high CD62L values. Verification efforts established 87% sensitivity / 95% specificity for CD62L and 59% specificity for JCV index as predictors of PML. Using both parameters identifies less than 5% of natalizumab-treated patients 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 reduce PML incidence tenfold.

Authors/Disclosures
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��