AUTHOR=Chen Jiaying , Su Ben , Zhang Xinyue , Gao Chao , Ji Yajie , Xue Xiaohong 

TITLE=Mendelian randomization suggests causal correlations between inflammatory cytokines and immune cells with mastitis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1409545

DOI=10.3389/fimmu.2024.1409545

ISSN=1664-3224

ABSTRACT=Previous studies have reported that immunoinflammatory responses have associations with mastitis. Here, we aimed to further figure out whether circulating inflammatory cytokines and immune cells causally impact mastitis liability.The two-sample Mendelian randomization made use of genetic variances of 91 inflammatory cytokines from a large publicly available genome-wide association study (GWAS) containing 14,824 participants, 731 immunophenotypes data from 3,757 individuals as exposures separately, and mastitis from a GWAS summary (1880 cases and 211699 controls of European ancestry) as outcome. The primary analysis applied the inverse-variance weighted (IVW) method to estimate causal influences, with MR-Egger, weighted median, weighted mode and simple mode as supplementary approaches. Heterogeneity and pleiotropy were evaluated by the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test.The results indicated that CX3CL1 may be suggestively relevant to the risk of mastitis (odds ratio, OR = 1.434, 95% CI = 1.142~1.800, pP = 0.002). Moreover, three immunophenotypes were identified as having a potential causal link to mastitis (p < 0.05). Significantly, CD28-CD8dim %CD8dim (OR = 1.058, 95% CI = 1.024 ~ 1.093, pP = 0.0006) and CD45 on CD33br HLA DR+ (OR = 1.097, 95% CI = 1.039 ~ 1.157, pP = 0.0008) were found to induce mastitis possibly. Conversely, CD39+ secreting Treg AC (OR = 0.929, 95% CI = 0.884~ 0.978, pP = 0.005) pertained to protective factors of mastitis. Cochran's Q test and MR-Egger intercept test indicated no significant heterogeneity (p > 0.05) or pleiotropy (p > 0.05), supporting the robustness and reliability of our findings.