Frontiers in immunology
Combination of iKIR missing ligand hypothesis and HLA-B T/T genotypes as predictive biomarkers for recurrent pregnancy loss: a novel algorithmic approach
By Laborda RG, Subhi-Issa N, Muñoz EF and 9 others.
Abstract
Introduction
Natural killer (NK) cell alloreactivity at the maternal-fetal interface is regulated by killer cell immunoglobulin-like receptors (KIR) and CD94/NKG2A receptors. A dimorphism at position -21 of the HLA-B leader peptide (-21M/-21T) biases NK education toward NKG2A (when -21M supplies HLA-E-binding peptides) or toward KIR (when -21T fails to do so). We evaluated whether maternal HLA-B leader genotype and inhibitory KIR (iKIR) missing-ligand (ML) status are associated with unexplained recurrent reproductive failure (uRF).
Methods
Retrospective case-control study comparing recipient HLA-B leader genotype (M+ versus T/T) and iKIR ML across HLA-C groups with outcomes in uRF patients versus healthy controls. 77 women with uRF (43 recurrent pregnancy loss [RPL], 34 recurrent implantation failure [RIF]) and 75 healthy multiparous controls. Maternal KIR, HLA-B and HLA-C genotypes were typed from peripheral blood using Luminex-based SSP/SSO assays.