The expression of L-selectin (CD62L) on specific T cells in peripheral blood in patients with relapsing forms of multiple sclerosis (MS) does not predict the risk of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment reliably, according to findings published January 26 in Neurology.
These findings contradict those of a previous preliminary study that used a different analytical technique. Investigators in the earlier study found a decrease in the percentage of CD4- and CD3-positive T cells expressing CD62L at least four months and often two years before PML diagnosis. They concluded that measuring the percentage of CD4- and CD3-positive T cells expressing CD62L “may improve stratification of patients taking natalizumab who are at risk for developing PML.”
Linda A. Lieberman, PhD, a research scientist at Biogen in Cambridge, Massachusetts, and colleagues sought to confirm the findings, enhance the reproducibility of the CD62L assay, “and potentially enable the deployment of CD62L as a biomarker for PML in a global setting.” The investigators, however, did not find a significant difference in the percentage of CD62L in cryopreserved peripheral blood mononuclear cells between 104 patients with relapsing forms of MS who received natalizumab and did not develop PML, and 21 patients who developed PML.
In the current study, the investigators detected a large range of CD62L (ie, 0.31% to 68.4%) in a subset of natalizumab-treated MS patients without PML at two time points at least six months apart. Because CD62L and the chemokine receptor CCR7 are coexpressed on CD4- and CD3-positive T cells, the researchers also examined the level of variation in simultaneous measurements of CD62L and CCR7 on the same cells at two separate time points in the same patients. They found that CD62L expression varied substantially, whereas CCR7 varied little, and the difference between the two was significant, “signifying that CD62L is not a stable outcome measure,” they wrote.
Dr. Lieberman and her colleagues also confirmed a positive correlation between lymphocyte viability and CD62L expression, which highlights the “technique-driven variability of the assay” used in the preliminary study.
In patient samples collected at least six months before PML diagnosis, the percentage of CD62L did not discriminate significantly between non-PML and active PML (defined as 0 to 6 months prior to diagnosis). The median percentage of CD62L varied according to the viability of cryopreserved CD4- and CD3-positive T cells. Median percentage of CD62L was no different between non-PML and pre-PML samples with lymphocyte viability greater than 75% (25.9% vs 26.3%, respectively), but was significantly lower than with non-PML and pre-PML samples with lymphocyte viability less than 75% (10.55% and 5.41%). There was no difference in lymphocyte viability between non-PML and pre-PML samples.
In a case–control comparison of patients receiving natalizumab who had multiple pre-PML samples, nine patients who developed PML had CD62L levels that in most samples were similar to those of nine matched control patients without PML.
Examination of samples from healthy controls demonstrated that CD62L also varied significantly in various disease states, such as after influenza vaccination and during hospitalization for total knee replacement surgery or methicillin-resistant Staphylococcus aureus infection, the researchers found.
—Jeff Evans