The effect of disease modifying therapies on CD62L expression in multiple sclerosis

Abstract

Background: The increasing armamentarium of disease-modifying therapies in multiple sclerosis is accompanied by potentially severe adverse effects. The cell-adhesion molecule CD62L, which facilitates leukocyte extravasation, has been proposed as a predictive marker for treatment tolerability. However, pre-analytical procedures might impact test results, thereby limiting its clinical usability. Whether the immediate analysis of CD62L expression of peripheral blood mononuclear cells can aid treatment decision making is yet unclear.

Objective: To investigate the effect of various disease-modifying therapies in multiple sclerosis on CD62L expression of CD3⁺CD4⁺ peripheral blood mononuclear cells in freshly collected blood samples.

Methods: We collected peripheral blood samples from patients with clinically isolated syndrome and multiple sclerosis (baseline/follow up n = 234/n = 98) and healthy controls (n = 51). CD62L⁺CD3⁺CD4⁺ expression was analysed within 1 hour by fluorescence-activated cell sorting.

Results: CD62L⁺CD3⁺CD4⁺ expression was significantly decreased in patients treated with natalizumab (n = 26) and fingolimod (n = 20) and increased with dimethyl-fumarate (n = 15) compared to patients receiving interferon/glatiramer acetate (n = 90/30) or no disease-modifying therapies (n = 53) and controls (n = 51) (p<0.001). CD62L expression showed temporal stability during unchanged disease-modifying therapy usage, but increased after natalizumab withdrawal and decreased upon fingolimod introduction.

Conclusion: CD62L⁺CD3⁺CD4⁺ expression is altered in patients treated with different disease-modifying therapies when measured in freshly collected samples. The clinical meaning of CD62L changes under disease-modifying therapies warrants further investigation.

Keywords: CD62L; clinically isolated syndrome; disease-modifying therapies; immunology; lymphocytes; multiple sclerosis.

Figure 1.

CD62L expression of CD3⁺CD4⁺ PBMCs in CIS/MS patients receiving different types of DMTs and healthy controls. (a) CD62L expression was significantly decreased with the use of natalizumab (n = 26) and fingolimod (n = 20), and significantly increased with the use of dimethyl fumarate (n = 15) compared to all other DMT subgroups and healthy controls (multi-comparison model p < 0.001). The data shown refer to baseline measurements. (b) Longitudinal measurements showed no overall alteration of CD62L expression in patients with stable DMT usage (n = 91; time interval median 113, IQR 77–163 days). (c) Effects of natalizumab and fingolimod on CD62L expression were visible in longitudinal PBMC samples of patients upon natalizumab withdrawal (n = 2, dotted lines; natalizumab treatment until 5.9 and 6.8 years) or after fingolimod initiation (n = 6, other/none DMT-treated before). In one patient, CD62L expression was measured when switching from natalizumab to fingolimod with a 2-month interim period. CIS: clinically isolated syndrome; DMF: dimethyl fumarate; DMTs: disease-modifying therapies; FTY: fingolimod; IFN/GA: interferon beta/glatiramer acetate; IQR: interquartile range; MS: multiple sclerosis; NTZ: natalizumab; PBMCs: peripheral blood mononuclear cells. Significance (p < 0.05) was analysed by Kruskal-Wallis test with Dunn’s post-hoc test, or Wilcoxon signed-rank test.