l -Selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients

Abstract

The cell-based assessment of the percentage of l-selectin-expressing CD4 T cells could provide an urgently needed biomarker for individual PML risk assessment.

Immunological biomarkers identifying natalizumab-treated multiple sclerosis patients at risk of progressive multifocal leukoencephalopathy

“…The presence of a very low percentage of these cells was highly correlated with the risk of developing PML in the group with available pre-PML samples when compared with non-PML natalizumab-treated patients. These data demonstrated that the cell-based assessment of the percentage of L-selectin-expressing CD4 + T cells has the possibility of providing a biomarker for an individualized natalizumab-related PML risk assessment, and perhaps also for HIV-associated PML risks (Schwab et al, 2013;Schneider-Hohendorf et al, 2014).…”

“…L-selectin, which acts as a "homing receptor" for lymphocytes to enter secondary lymphoid tissues via high endothelial venules, was evaluated in a study that included 289 subjects with MS; 224 patients had been treated for 18-80 months with natalizumab, 21 had received glatiramer acetate or interferon beta, 28 were untreated MS subjects and 16 were natalizumab-treated patients that developed PML (Schwab et al, 2013). In eight of them, blood samples were available also prior to the diagnosis of PML and in three before natalizumab therapy initiation.…”

Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis

“…Even for some time after the cessation of natalizumab, a certain risk of PML remains and pharmacovigilance should be continued [63,64]. There are increasing efforts to further refine PML risk stratification, especially for patients that convert to anti-JCV antibody positive status while on natalizumab, using antibody indices in serum and cerebrospinal fluid, as well as other approaches [65][66][67][68].…”

Immunology of progressive multifocal leukoencephalopathy

“…However, JCV viremia was observed in patients that were seronegative for anti-JCV VP1 antibodies, indicating that testing JCV-specific antibodies might not be sufficient to stratify the risk for some natalizumab-treated MS patients (Major et al, 2013). Interestingly, serum JCV VP1-specific antibody levels are increased in patients at onset of natalizumab-associated PML compared to natalizumab-treated MS patients (Trampe et al, 2012;Warnke et al, 2013;Warnke et al, 2014). PML survivors in the context of AIDS show significant increases in JCV-specific T cells and IgG responses in the peripheral blood, which are positively correlated with peripheral CD4 + T cell counts (Khanna et al, 2009).…”