Cross-sectional analysis of peripheral blood mononuclear cells in lymphopenic and non-lymphopenic relapsing-remitting multiple sclerosis patients treated with dimethyl fumarate.

BACKGROUND

Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune disorder of the central nervous system. Dimethyl Fumarate is a disease-modifying medication used to treat RRMS patients that can induce lymphopenia. We aimed to immunophenotype peripheral blood mononuclear cells (PBMC) in RRMS patients cross-sectionally and examine the characteristics and modifications of lymphopenia over time.

METHODS

Characterization of PBMC was done by multiparametric flow cytometry. Patients had been on treatment for up to 4 years and were grouped into lymphopenic (DMF-L) and non-lymphopenic (DMF-N) patients.

RESULTS

Lymphopenia affected the cell population changes over time, with other patient characteristics (gender, age, and previous treatment status) also having significant effects. In both lymphopenic and non-lymphopenic patients, PBMC percentages were reduced over time. While overall T and B cells frequencies were not affected, males, older patients and untreated patients had significant changes in B cell subpopulations over time. CD4+ to CD8+T cell ratio increased significantly in lymphopenic patients over time. CD4-CD8-T cell population was similarly reduced in both lymphopenic and non-lymphopenic patients, over time. While the monocyte and NK overall populations were not changed, non-classical monocyte subpopulation decreased over time in lymphopenic patients. We also found CD56-CD16+ and CD56-CD16- NK cells frequencies changed over time in lymphopenic patients. Immune populations showed correlations with clinical outcomes measured by EDSS and relapse rate. Analysis of the overall immunophenotype showed that, while groups divided by other patient characteristics showed differences, the lymphopenia status overrode these differences, resulting in similar immunophenotype within DMF-L.

CONCLUSIONS

Our data provide evidence that under the same therapy, lymphopenia affects how the immunophenotype changes over time and can override the differences associated with other patient characteristics and possibly mask other significant changes in the immune profile of patients.