CD4+CD62L+ cells: A monitoring marker of fingolimod dosage in multiple sclerosis. Issue 1 (28th September 2019)

• Record Type: Journal Article
• Authors: Tanaka, Masami; Kinoshita, Masako; Tomita, Yutaka; Tanaka, Keiko
• Is Part Of: Clinical & experimental neuroimmunology. Volume 11:Issue 1(2020)
• Page Start: 26
• Page End: 32
• Publication Date: 2019-09-28
• Subjects: CD62L -- fingolimod -- lymphocyte subset -- multiple sclerosis -- personalized medicine; 616.80479
• DOI: 10.1111/cen3.12545
• Languages: English
• ISSNs: 1759-1961

Abstract

Abstract: Objectives: Fingolimod (FTY) potentially inhibits the disease activity of multiple sclerosis (MS), but induces severe lymphocytopenia that might be related viral infections, including progressive multifocal leukoencephalopathy. We use a reduced dosage of FTY treatment to avoid its cessation because of lymphocytopenia. FTY inhibits the egress of CD62L + cells from lymph nodes, and the number of CD4 + CD62L + cells, a major population of CD62L + cells, in blood is a maker to evaluate the strength of FTY action in patients with MS treated by intermittent drug holidays of FTY. Methods: A total of 24 Japanese patients with MS were treated with variable dosages of FTY initially based on the number of lymphocytes, and then changed to CD4 + CD62L + cell counts as a marker. Fluorescence‐activated cell sorting analysis was used to evaluate the number of CD4 + CD62L + cells in fresh blood of 21 MS patients treated with FTY for 30–94 months, including the mean period of 27.5 months of daily administration. Results: The CD4 + CD62L + cell counts and the proportion of patients with <2% CD4 + CD62L + cells in total lymphocytes declined from 12 ± 13 cells/mm 3 (median 8 cells/mm 3 ) to 31 ± 4 cells/mm 3 (median 27 cells/mm 3 ) and 61.5% to 0%, respectively, after further dosage reduction. Their annual relapse rates were kept to <0.03, even after inducing CD4 + CD62L+ counts as a monitoring marker. The target range of CD4 + CD62L + cells on reduction of FTY dosage was 10–80 cells/mm 3 . Conclusions: It is critical to monitor CD4 + CD62L + cells rather than total lymphocyte count to avoid excessive FTY administration. Abstract : CD4 + CD62L + cells could be a better marker than total lymphocyte counts to avoid excessive dosage in multiple sclerosis patients treated by a reduced dosage of fingolimod with intermittent drug holidays. The proportion of patients with <2% CD4/62L cells in total lymphocytes declined from (a) 61.5% to (b) 12.5%, and then to (c) 0% after further dosage reduction.