Combination of iKIR missing ligand hypothesis and HLA-B T/T genotypes as predictive biomarkers for recurrent pregnancy loss: a novel algorithmic approach

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).