title: CD62L is not a reliable biomarker for predicting PML risk in natalizumab-treated R-MS patients.
abstract: OBJECTIVE
  To assess if the percentage of CD3(+)CD4(+)CD62L(+) cells in cryopreserved peripheral blood mononuclear cells (PBMCs) (here termed %CD62L) can predict risk of developing progressive multifocal leukoencephalopathy (PML) and better inform the physician for benefit-risk assessment of natalizumab treatment decisions in a global setting.
  
  
  METHODS
  Cryopreserved PBMCs from 21 natalizumab-treated patients who developed PML and 104 matched natalizumab-treated patients with multiple sclerosis (MS) without PML collected as a part of Biogen clinical trials were retrospectively examined for CD3, CD4, CCR7, CD45RA, and CD62L by flow cytometry.
  
  
  RESULTS
  In this cohort, %CD62L in natalizumab-treated patients did not predict PML risk. Natalizumab-treated patients with MS without PML showed highly variable %CD62L upon serial sampling. In the STRATA study, the distribution of %CD62L in samples collected more than 6 months before a PML diagnosis, at diagnosis, and in natalizumab-treated patients without PML overlapped. No statistical threshold for risk could be determined. In addition, we demonstrated that lymphocyte viability strongly affects %CD62L, supporting previous reports that %CD62L is inherently unstable following cryopreservation and is sensitive to sample collection.
  
  
  CONCLUSIONS
  Data from this well-controlled cohort of natalizumab-treated patients indicate that %CD62L is not a biomarker of PML risk.
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Lieberman
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Wanyong
authors.initials: W
authors.lastname: Zeng
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Carol
authors.initials: C
authors.lastname: Singh
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wang
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Otipoby
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Christine
authors.initials: C
authors.lastname: Loh
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Plavina
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Leonid
authors.initials: L
authors.lastname: Gorelik
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.affiliation: From Discovery Research, Biogen, Cambridge, MA. Ellen.Cahir-McFarland@biogen.com.
authors.forename: Ellen
authors.initials: E
authors.lastname: Cahir-McFarland
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001793:Blood Preservation; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D015925:Cryopreservation; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D019041:L-Selectin / Q000097:blood*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000188:drug therapy; D000069442:Natalizumab / Q000009:adverse effects*; D011379:Prognosis; D012189:Retrospective Studies; D012306:Risk; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D000069442:Natalizumab; D019041:L-Selectin