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Association between soluble L-selectin and anti- JCV antibodies in natalizumabtreated relapsing-remitting MS patients

      Background: Long-term treatment of Natalizumab in relapsing-remitting MS (RRMS) patients is associated with the risk of developing progressive multifocal leukoencephalopathy (PML), a JC virus (JCV)-mediated disease of the CNS. Measurement of anti-JCV antibodies in natalizumab-treated MS patients is used for the estimation of patient’s risk for PML and lower percentage of L-selectin CD4 + T cells has been suggested as a biomarker for individual PML risk assessment.
      Objective: L-selectin is also present as functionally active soluble form in the blood upon shedding from the cell surface of activated T cells. Therefore, our aim was to examine whether the levels of soluble L-selectin (sL-selectin) can predict the risk of PML in natalizumab-treated RRMS patients.
      Methods: The levels of sL-selectin and anti-JCV antibody indices in sera were measured from a total of 99 subjects of whom 44 RRMS patients were treated with natalizumab, 30 patients with IFN-β and 25 subjects were healthy controls.
      Results: The significant correlation was found between the levels of sL-selectin and JCV-antibody indices in the natalizumab-treated patients (r = 0.402; p = 0.007; n = 44), but not in those treated with IFN-β. This correlation became even stronger in JCV-seropositive patients treated with natalizumab longer than 18 months therapy (r = 0.529; p = 0.043; n = 15). Moreover, significantly higher level of sL-selectin was detected in the high-risk group (JCV antibody index >1.5) compared to that with low risk group (JCV antibody index ≤1.5) for developing PML.
      Conclusion: Our data suggest that the measurement of sL-selectin should be evaluated further as a potential biomarker for predicting the risk of developing PML.