Exploring the immunological landscape of osteomyelitis through mendelian randomization analysis.

Abstract

Osteomyelitis is a severe bone marrow infection, whose pathogenesis is not yet fully understood. This study aims to explore the causal relationship between immune cell characteristics and osteomyelitis, hoping to provide new insights for the prevention and treatment of osteomyelitis. Based on two independent samples, this study employed a two-sample Mendelian randomization (MR) analysis to assess the causal relationship between 731 immune cell characteristics (divided into seven groups) and osteomyelitis. Genetic variants were used as proxies for risk factors to ensure that the selected instrumental variables meet the three key assumptions of MR analysis. Genome-Wide Association Studies (GWAS) data for immune characteristics were obtained from the public GWAS catalog, while data for osteomyelitis was sourced from the FinnGen. At a significance level of 0.05, 21 immune phenotypes were identified as having a causal relationship with osteomyelitis development. In the B cell group, phenotypes such as Memory B cell % B cell (percentage of memory B cells within the total B cell population, % finger cell ratio), CD20- %B cell (percentage of B cells that do not express the CD20 marker on their surface), and Memory B cell % lymphocyte showed a positive causal relationship with osteomyelitis, while Naive-mature B cell %B cell and IgD-CD38-absolute cell counts (AC) phenotypes showed a negative causal relationship. In addition, specific immune phenotypes in the conventional dendritic cells (cDCs) group, Myeloid cell group, TBNK (T cells, B cells, natural killer cells) cell group, T cell maturation stage, and Treg cell group also showed significant associations with osteomyelitis. Through reverse MR analysis, it was found that osteomyelitis had no significant causal impact on these immune phenotypes, suggesting that the occurrence of osteomyelitis may not affect these immune cell phenotypes. To our knowledge, this is the first study to shed light on the causal relationship between specific immune cell characteristics and the development of osteomyelitis, thereby providing a new perspective to understand the immune mechanism of osteomyelitis. These findings are significant for formulating targeted prevention and treatment strategies, and hold promise to improve the treatment outcomes for patients with osteomyelitis.