Examining the causal relationship between circulating immune cells and the susceptibility to osteomyelitis: A Mendelian randomization study

Abstract

Background: Osteomyelitis is considered as a deleterious inflammatory condition affecting the bone, primarily attributed to pathogenic infection. However, the underlying factors predisposing individuals to osteomyelitis remain incompletely elucidated. The immune system plays a multifaceted role in the progression of this condition, yet previous observational studies and randomized controlled trials investigating the association between circulating immune cell counts and osteomyelitis have been constrained. In order to address this knowledge gap, we conducted a Mendelian randomization (MR) analysis to evaluate the impact of diverse immune cell counts on the risk of developing osteomyelitis.

Methods: In our study, we utilized single nucleotide polymorphisms (SNPs) that have been strongly linked to circulating immune cells or specific lymphocyte subtypes, as identified in large-scale genome-wide association studies (GWAS). These SNPs served as instrumental variables (IVs) for our MR analysis. We employed a more relaxed clumping threshold to conduct MR analysis on several related lymphocyte subtypes. To estimate causal effects, we utilized the Wald ratio, as well as the random-effects inverse variance weighted (IVW) and weighted median (WM) methods. To enhance the credibility of our results, we performed F-statistic calculations and a series of sensitivity analyses.

Results: Our findings revealed a significant correlation between the absolute count of circulating lymphocytes and the risk of osteomyelitis [odds ratio(OR) 1.20；95 % confidence interval (CI), 1.08-1.32；P = 0.0005]. Furthermore, we identified a causal relationship between the absolute count of CD8⁺ T cells and susceptibility to osteomyelitis (OR 1.16; 95 % CI, 1.04-1.30; P = 0.0098). Importantly, these findings remained robust across a wide range of sensitivity analyses.

Conclusion: Through our MR analysis, we have provided evidence supporting a causal relationship between genetic predisposition to higher circulating immune cell counts and an increased risk of osteomyelitis. Specifically, our findings highlight the association between elevated CD8⁺ T cell counts and a heightened susceptibility to osteomyelitis. These results offer valuable insights for the future exploration of immunotherapy approaches in the management of osteomyelitis.

Keywords: CD8(+) T cells; Circulating immune cells; Lymphocytes; Mendelian randomization (MR); Osteomyelitis.