KIR genes influence endometrial dysbiosis, chronic endometritis and antibiotic response in infertile women

Is there a relationship between KIR genotypes/genes and the prevalence of the microbial-mediated inflammatory conditions endometrial dysbiosis and chronic endometritis, and any potential effect on the response to antibiotic treatment in infertile women?

Retrospective cohort study of women of European ancestry (n = 308) undergoing assisted reproductive treatment with donated oocytes. All participants had KIR genotyping results and had been evaluated for endometrial dysbiosis, chronic endometritis, or both, using the EMMA assays, ALICE assays, or both. Patients were stratified by KIR genotype (AA, AB, BB), telomere regions and by the presence or absence of the KIR2DS1 and KIR3DS1 genes. Prevalence of endometrial dysbiosis and chronic endometritis, and number of antibiotic cycles required to normalize endometrial microbiota, resolve chronic endometritis, or both were evaluated.

Patients carrying KIR2DS1 and Tel-B showed significantly lower prevalence of endometrial dysbiosis (54.7% versus 75.2%, P = 0.0017; 46.8% versus 66.7%, P = 0.0089) and chronic endometritis (19.4%, versus 33.3%, P = 0.015; 6.7%, versus 17%, P = 0.0262). Presence of KIR3DS1 was associated with reduced endometrial dysbiosis prevalence (75.7% versus 56.0%, P = 0.0025). KIR genotype was not significantly associated with these conditions. KIR2DS1+ and Tel-B patients required fewer antibiotic cycles to achieve a normal endometrial biopsy (1.2 ± 0.4 versus 1.7 ± 0.7, P = 0.0026; 1.0 ± 0.0 versus 1.7 ± 0.8; P < 0.0001).

The presence of specific activating KIR genes and regions is linked to lower prevalence of endometrial dysbiosis and chronic endometritis, and to a better response to antibiotic treatment. Proper immune control, mediated by the appropriate activation of uterine natural killer cells through specific KIRs, is required for effective antimicrobial defence in the endometrium.