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 SG, Zipp F, Gold R, Du Pasquier RA, Kleinschnitz C, Jacobi A, Comabella M, Bertolotto A, Brassat D, Wiendl H. PML risk stratification using anti-JCV antibody index and L-selectin. Mult Scler. 2015. pii: 1352458515607651. [Epub ahead of print]
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 aetiology. A risk algorithm incorporating both biomarkers could strongly reduce PML incidence.
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 aetiology. A risk algorithm incorporating both biomarkers could strongly reduce PML incidence.
We have seen that a number of posts find low CD62L as a risk factor for developing PML
Multiple Sclerosis Research: Low L-selectin as a risk factor …
28 Aug 2015 http://multiple-sclerosis-research.blogspot.com/
28 Aug 2015 http://multiple-sclerosis-research.blogspot.com/
Multiple Sclerosis Research: Finding a marker of Risk of PML
27 Aug 2013 http://multiple-sclerosis-research.blogspot.com/
27 Aug 2013 http://multiple-sclerosis-research.blogspot.com/
Will this come into routine practice as a part of risk management
Dear MD,
As a Natalizumab user, is there any way that I could get tested for this number?
It something any heamatology department can do if they can see immune subsets but maybe NDG or ProfG can comment on whether they believe that the sensitivity specificity is good enough to be informative
Dear MD,
I understand that it is only beta release level metric, but would be interested.