RESULTS: This case-control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing.
CONCLUSIONS: Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.
结果:这项病例对照研究揭示了20个新的和31个复发的致病变异。微生物组荟萃分析显示不同的微生物种群,共生微生物群减少,以及与CI相关的致病物种的更高定植;这些与外周血单核细胞中炎性细胞因子和Th17-和JAK/STAT信号通路的产生增加相关。在CI患者的伤口中,我们确定了微生物群的特定变化和炎症途径的改变,这可能是伤口愈合受损的原因。
结论:一起,这项研究增强了我们对微生物的理解,免疫学,和CI的分子特性,并应为改善CI患者的治疗管理提供关键信息。