The peripheral immune cell counts and mouth ulcers: A two-sample Mendelian randomization study

Objective: This study explored the causal association of peripheral immune cell counts with mouth ulcers (MUs) by two-sample Mendelian Randomization. Design: The counts of 12 circulating immune cell types (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils, CD4+ cells, CD8+ cells, unswitched memory B cells, NK cells, B cells and a derived ratio (CD4+/CD8+)) were determined as the exposure. MUs were the outcome. The analysis was conducted mostly using the inverse-variance weighted (IVW) approach. MR Egger, weighted median, weighted mode and simple mode were used to detect the horizontal pleiotropy. Results: The IVW results for leukocytes and lymphocyte counts were OR = 0.93, 95 % CI = 0.88-0.98, p = 0.0115 and OR = 0.91, 95 % CI: 0.84-0.98, p = 0.0150, respectively. The Wald ratio result for CD4+ cell and CD8+ cell counts were OR = 0.70, 95 % CI: 0.65-0.75, p = 1.05 x 10-20 and OR = 1.25, 95 % CI: 1.19-1.31, p = 9.99 x 10-21, respectively. Conclusions: This study supports a causal effect of peripheral immune cell counts on MUs. Higher leukocyte, lymphocyte and CD4+ cell counts can protect against MUs, but higher CD8+ cell counts enhance the risk of MUs. This finding confirms host immune factors play a crucial role in the aetiology of MUs.