CD62L (L-selectin) is Not a Reliable Biomarker for Predicting Risk of Progressive Multifocal Leukoencephalopathy in Natalizumab-Treated Multiple Sclerosis Patients (P4.039)

OBJECTIVE: The goal of this study was to assess in an independent cohort whether the percent of CD62L-expressing CD4+ T cells ([percnt]CD62L) in cryopreserved peripheral blood mononuclear cells (PBMC) predicts the risk of progressive multifocal leukenchephalopathy (PML) in natalizumab-treated multiple sclerosis (MS) patients. BACKGROUND: The presence of anti-JCV antibodies in serum, use of immunosuppressants prior to natalizumab treatment and duration of natalizumab treatment are known risk factors for developing PML. Recently, a decreased [percnt]CD62L in cryopreserved PBMC was proposed as a novel marker for predicting an increased risk of PML in natalizumab-treated MS patients.DESIGN/METHODS: Cryopreserved PBMC from 21 natalizumab-treated MS patients who later developed PML and 104 matched non-PML controls collected as part of Biogen Idec clinical trials were retrospectively examined for CD3, CD4, CCR7, CD45RA and CD62L by flow cytometry. Both cross-sectional and longitudinal analysis of the data was performed.RESULTS: [percnt]CD62L was variable in non-PML control natalizumab-treated MS patients on repeat sampling. Pre-PML (collected 蠅 6 months prior to PML diagnosis) and non-PML populations had overlapping [percnt]CD62L levels, and three out of nine PML patients with longitudinal pre-PML samples exhibited high [percnt]CD62L. Measurements of [percnt]CD62L were affected by sample collection, processing procedure, and assay methodologies. Further, [percnt]CD62L was significantly lower in samples with lymphocyte viability below 75[percnt]. CONCLUSIONS: Data from this well controlled cohort suggests that determination of [percnt]CD62L on CD4+ T cells in cryopreserved PBMCs is not a reliable biomarker of PML risk in natalizumab-treated MS patients.Study Supported by: Biogen Idec Disclosure: Dr. Lieberman has received personal compensation for activities with Biogen Idec as an employee. Dr. Zeng has received personal compensation for activities with Biogen Idec as an employee. Dr. Plavina has received personal compensation for activities with Biogen Idec as an employee. Dr. Singh has received personal compensation for activities with Biogen Idec as an employee. Dr. Otipoby has received personal compensation for activities with Biogen Idec as an employee. Dr. Loh has received personal compensation for activities with Biogen Idec as an employee. Dr. Gorelik has received personal compensation for activities with Biogen Idec and Coronado Biosciences as an employee. Dr. Cahir-McFarland has received personal compensation for activities with Biogen Idec as an employee.