Increased cytotoxic natural killer cells in the endometrium alone cannot be considered the immunological cause of recurrent miscarriage.

Data de publicació: 22/02/2023 Data Ahead of Print: 22/02/2023

Autors de IIS La Fe

Autors aliens a IIS La Fe

Cuadrado-Torroglosa, Isabel
Pacheco, Alberto
Barrio, Ana
Aparicio, Pilar
Garcia-Velasco, Juan Antonio

Grups d'Investigació

Biología Reproductiva y Bioingeniería en Reproducción Humana

Leader

Nicolás Garrido Puchalt
Endocrinología Reproductiva e Infertilidad

Leader

José Remohí Giménez
Medicina Reproductiva

Investigador Principal

José Morales Roselló

Abstract

OBJECTIVE: To study the distribution and gene expression of endometrial immune cells populations, especially NK subsets, between assisted reproduction techniques (ART) patients and healthy donors; and to explore a possible relationship of these results with patients' Killer Immunoglobulin-like Receptor (KIR) genotypes and KIR-Human Antigen Leukocyte-C (HLA-C) binding. DESIGN: Prospective observational cohort study. SUBJECTS: Participants included thirty-nine women with recurrent miscarriages who had undergone in vitro fertilization cycles (IVF) with donated oocytes as well as twenty-one healthy oocyte donors with proven fertility. INTERVENTION: Endometrial biopsies were collected from both patients and donors and, additionally, the KIR genotypes of the ART patients were analyzed. MAIN OUTCOME MEASURES: Endometrial gene expression (CD antigens, anti- and pro-inflammatory interleukins) as well as the number and percentage of regulatory T-cell (Treg) and natural killer (NK) cell populations in patients and donors were determined. Subsequently, the results obtained were categorized in the group of patients by KIR genotype. KIR-HLA-C binding was also examined in patients, considering their KIRs. RESULTS: A higher percentage of CD56(dim)CD16(+) NK cells (p<0.013) was observed in patients, compared to healthy donors. Nevertheless, when categorizing patients by KIR genotype and comparing between KIR AA (35.9%), AB (43.6%) and BB (20.5%) groups, no statistically significant difference was observed in either endometrial gene expression or in any of the immune cell populations analyzed. Finally, no differences in binding between KIR and HLA-C molecules were registered among these three sets of patients. CONCLUSIONS: The reported increase of NK cells with a cytotoxic profile in the endometrium of women with a history of recurrent miscarriages cannot alone explain these events, as no relationship is observed between such cellular rise and the KIR genotypes, which individually, and in combination with the different HLA-C alleles, have also been associated, by previous studies, with negative reproductive outcomes.