Author response: Prospective validation of the PML risk biomarker l -selectin and influence of natalizumab extended intervals

Abstract

On behalf of all authors, we would like to thank Mr. Tugemann for his interest in our article.1 It is correct that acute progressive multifocal leukoencephalopathy (PML) can, in some circumstances, lead to high(er) CD62L values. However, as the study was conducted prospectively and, more importantly, alongside treatment, we reported all results of samples shipped to us back to the treating physicians. At the time of measurement and reporting, we were not aware of the patients' disease state. Because this is the situation to be expected in postmarketing settings, we chose to report all measured values, even if the samples turned out to be less than 6 months before PML diagnosis. Although the exclusion of these samples would indeed have led to a perfect sensitivity with the threshold of 36.05, we believed that it would not accurately reflect the real-world situation. Similarly, we chose not to focus on other PML risk stratification factors such as previous immune suppression or anti-JC virus antibody serostatus because we could not rely on having this information for all samples shipped to us. We, therefore, decided to report on the feasibility of measuring one biomarker rather than presenting a holistic approach for risk stratification using all available markers, which was addressed before.2 As supported by this study, CD62L was proven to be a useful biomarker for PML risk stratification also in the real-world setting but could also help with monitoring immunologic changes because of natalizumab-extended interval dosing. Owing to its initial detection in a retrospective cohort, the validated methodology3 still requires a mandatory freeze/thaw cycle, thereby limiting its widespread use. However, we would be more than happy if methodological improvements could be achieved here.