Natalizumab treatment alters the expression of T-cell trafficking marker LFA-1 alpha-chain (CD11a) in MS patients

作者：Jilek Samantha; Mathias Amandine; C****es Mathieu; Lysandropoulos Andreas; Pantaleo Giuseppe; Schluep Myriam; Du Pasquier Renaud A^*

来源：Multiple Sclerosis, 2014, 20(7): 837-842.

DOI：10.1177/1352458513513208

• Adverse effects
• CD11a
• cellular immunity
• CXCR3
• LFA-1
• integrins
• longitudinal study
• natalizumab
• progressive multifocal encephalopathy
• T cell
• VLA-4

Objective: To determine the long-term effect of natalizunnab (NTZ) treatment on the expression of integrins and chenmokine receptors involved in the migration of T cells towards the central nervous system (CNS).
Methods: We drew the blood of 23 patients just before starting NTZ therapy and every 12 months thereafter, for up to 48 months of treatment. We assessed the ex-vivo expression of phenotype markers (CCR7 and CD45RA), CNS-addressing integrins (CD11a, CD49d and CD29) and chemokine receptors (CXCR3 and CCR6) in CD4+ or CD8+ T-cell subsets by flow cytometry.
Results: As compared to the pre-NTZ values, there was a marked increase in central memory (CCR7+/CD45RA-) CD4+ T cells and in effector memory (CCR7-/CD45RA-) CD8+ T cells at 12 and 24 months. In addition to an expected downregulation of both VLA-4 subunits (CD49d/CD29), we also found decreased T-cell expression of CXCR3 at 12 months, and of CD11a (LFA-1 alpha(L) subunit) at 12 months, but mostly at 24 months of NTZ treatment.
Conclusion: Our data show a nadir of CD11a expression at 2 years of NTZ treatment, at the peak of incidence of progressive multifocal leukoencephalopathy (PML), indirectly suggesting that a lack of these molecules may play a role in the onset of PML in NTZ-treated patients.

• 出版日期2014-6