Peripheral immunological characteristics of spontaneous pneumothorax: a Mendelian randomization study

Spontaneous pneumothorax (SP) is a common pleural disease in adolescents and adults. However, the role of immunological characteristics in the pathogenesis of SP remains unclear. This study aims to clarify the causal associations between circulating immune cells, lymphocyte subgroups, and SP susceptibility.

Employing Mendelian randomization (MR), the causal association between circulating immune blood cells and lymphocyte subgroups on SP susceptibility have been assessed. Reverse MR analysis was used to further explore the causal relationship. The MR analysis ensured the reliability of the study results through the deletion of confounding single nucleotide polymorphisms (SNPs), heterogeneity testing, sensitivity analysis.

Seven immune cells and SP risk under stringent and lenient threshold conditions were identified. Eosinophils absolute count (AC) [odds ratio (OR) =1.0014, 95% confidence interval (CI): 1.0001-1.0014, P=0.02], memory B cell %B cell ratio (OR =1.008, 95% CI: 1.0002-1.0015, P=0.01), CD4⁺ T cell AC (OR =1.0014, 95% CI: 1.0003-1.0025, P=0.009), effector memory CD4⁺ T cell %T cell ratio (OR =1.0028, 95% CI: 1.0010-1.0046, P=0.003), and HLA-DR⁺CD8⁺ T cell %T cell ratio (OR =1.0019, 95% CI: 1.0004-1.0035, P=0.01) were identified as risk factors for increased susceptibility to SP. Conversely, CD8dim T cell AC (OR =0.9983, 95% CI: 0.9967-0.9999, P=0.03) and CD8dim natural killer T (NKT) %T cell ratio (OR =0.9982, 95% CI: 0.9965-0.9999, P=0.04) exhibited protective effects on SP. In natural killer (NK) cell subgroups and reverse MR analysis, no significance was found.

This study establishes a close causal relationship between immune cells and SP through genetic methods, providing a new perspective for understanding the pathophysiological mechanisms of SP.