{
  "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).\n\nMethods: 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.\n\nResults: The centromeric KIR AA haplotype was enriched in uRF versus controls (difference 24%, p=0.0056). iKIR-ML analysis showed higher frequency of KIR2DL2/3 with absent C1 ligands in uRF (p=0.015). The HLA-B −21 analysis revealed increased T/T homozygosity in uRF (p=0.0031). The combination of KIR2DL2/3 (absent C1) with −21 T/T was more prevalent in RPL (p=0.04).\n\nDiscussion: HLA-B −21 T/T and iKIR ML (absent C1 for KIR2DL2/3) may aid risk stratification in RPL. Findings warrant validation in larger cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Immunology, Hospital Clínico San Carlos, IdISSC",
    "Immunology, ORL and Ophthalmology Department, Medical Faculty, Universidad Complutense de Madrid",
    "Obstetrics and Gynecology Department, Hospital Clínico San Carlos",
    "Department of Clinical Immunology, Hospital Reina Sofia"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Raquel Gil Laborda"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nabil Subhi-Issa"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Eduardo de la Fuente Muñoz"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "María Palacios Ortega"
    },
    {
      "affs": [
        0
      ],
      "name": "María Guzman-Fulgencio"
    },
    {
      "affs": [
        0
      ],
      "name": "Angela Villegas Mendiola"
    },
    {
      "affs": [
        0
      ],
      "name": "MD Mansilla Ruiz"
    },
    {
      "affs": [
        2
      ],
      "name": "Lydia Pilar-Suarez"
    },
    {
      "affs": [
        2
      ],
      "name": "Ignacio Cristóbal García"
    },
    {
      "affs": [
        3
      ],
      "name": "Rafael González Fernández"
    },
    {
      "affs": [
        0
      ],
      "name": "Silvia Sánchez-Ramón"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Miguel Fernández-Arquero"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/erdwygf75dwrb.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1866398",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691304/?tool=EBI",
  "id": "erdwygf75dwrb",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1866398/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Reproductive System and Pregnancy"
    ]
  ],
  "openalex": "W7221147634",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691304/pdf/?tool=EBI",
  "pmcid": "PMC13691304",
  "pmid": null,
  "published": "2026-10-08",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/erdwygf75dwrb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1866398",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1866398/full"
    },
    {
      "first_seen": "2026-10-30T12:19:59Z",
      "native_id": "PMC:PMC13691304",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13691304"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Reproductive System and Pregnancy",
      "subfield": "immunology"
    }
  ],
  "title": "Combination of iKIR missing ligand hypothesis and HLA-B T/T genotypes as predictive biomarkers for recurrent pregnancy loss: a novel algorithmic approach",
  "title_text": "Combination of iKIR missing ligand hypothesis and HLA-B T/T genotypes as predictive biomarkers for recurrent pregnancy loss: a novel algorithmic approach",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:59Z",
  "url": "https://research.draconitic.com/paper/erdwygf75dwrb",
  "venue": "Frontiers in Immunology",
  "versions": []
}