Table_1_Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis.xlsx

Background

Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear.

Methods

Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed.

Results

MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4⁺ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25⁺⁺CD4⁺ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25⁺⁺CD4⁺ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25⁺⁺CD4⁺ T cell in CD4⁺ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25⁺⁺CD8⁺ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4⁺ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04).

Conclusions

This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.