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Fundaci\u00f3n","doi-asserted-by":"publisher","award":["04087\/GERM\/06"],"award-info":[{"award-number":["04087\/GERM\/06"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007801","name":"S\u00e9neca Fundaci\u00f3n","doi-asserted-by":"publisher","award":["10\/1964"],"award-info":[{"award-number":["10\/1964"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007801","name":"S\u00e9neca Fundaci\u00f3n","doi-asserted-by":"publisher","award":["04087\/GERM\/06"],"award-info":[{"award-number":["04087\/GERM\/06"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007801","name":"S\u00e9neca Fundaci\u00f3n","doi-asserted-by":"publisher","award":["Programa Nacional de Movilidad de Recursos Humanos, Plan Nacional de I-D+i 2008\u20132011"],"award-info":[{"award-number":["Programa Nacional de Movilidad de Recursos Humanos, Plan Nacional de I-D+i 2008\u20132011"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerio de Educaci\u00f3n","award":["04087\/GERM\/06"],"award-info":[{"award-number":["04087\/GERM\/06"]}]},{"name":"Ministerio de Educaci\u00f3n","award":["10\/1964"],"award-info":[{"award-number":["10\/1964"]}]},{"name":"Ministerio de Educaci\u00f3n","award":["04087\/GERM\/06"],"award-info":[{"award-number":["04087\/GERM\/06"]}]},{"name":"Ministerio de Educaci\u00f3n","award":["Programa Nacional de Movilidad de Recursos Humanos, Plan Nacional de I-D+i 2008\u20132011"],"award-info":[{"award-number":["Programa Nacional de Movilidad de Recursos Humanos, Plan Nacional de I-D+i 2008\u20132011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic liver rejection (CR) represents a complex clinical situation because many patients do not respond to increased immunosuppression. Killer cell immunoglobulin-like receptors\/Class I Human Leukocyte Antigens (KIR\/HLA-I) interactions allow for predicting Natural Killer (NK) cell alloreactivity and influence the acute rejection of liver allograft. However, its meaning in CR liver graft remains controversial. KIR and HLA genotypes were studied in 513 liver transplants using sequence-specific oligonucleotides (PCR-SSO) methods. KIRs, human leucocyte antigen C (HLA-C) genotypes, KIR gene mismatches, and the KIR\/HLA-ligand were analyzed and compared in overall transplants with CR (n = 35) and no-chronic rejection (NCR = 478). Activating KIR (aKIR) genes in recipients (rKIR2DS2+ and rKIR2DS3+) increased CR compared with NCR groups (p = 0.013 and p = 0.038). The inhibitory KIR (iKIR) genes in recipients rKIR2DL2+ significantly increased the CR rate compared with their absence (9.1% vs. 3.7%, p = 0.020). KIR2DL3 significantly increases CR (13.1% vs. 5.2%; p = 0.008). There was no influence on NCR. CR was observed in HLA-I mismatches (MM). The absence of donor (d) HLA-C2 ligand (dC2\u2212) ligand increases CR concerning their presence (13.1% vs. 5.6%; p = 0.018). A significant increase of CR was observed in rKIR2DL3+\/dC1\u2212 (p = 0.015), rKIR2DS4\/dC1\u2212 (p = 0.014) and rKIR2DL3+\/rKIR2DS4+\/dC1\u2212 (p = 0.006). Long-term patient survival was significantly lower in rKIR2DS1+rKIR2DS4+\/dC1\u2212 at 5\u201310 years post-transplant. This study shows the influence of rKIR\/dHLA-C combinations and aKIR gene-gene mismatches in increasing CR and KIR2DS1+\/C1-ligands and the influence of KIR2DS4+\/C1-ligands in long-term graft survival.<\/jats:p>","DOI":"10.3390\/ijms232012155","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T20:53:29Z","timestamp":1665608009000},"page":"12155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Killer Cell Immunoglobulin-like Receptors (KIR) and Human Leucocyte Antigen C (HLA-C) Increase the Risk of Long-Term Chronic Liver Graft Rejection"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-4313","authenticated-orcid":false,"given":"Isabel","family":"Legaz","sequence":"first","affiliation":[{"name":"Department of Legal and Forensic Medicine, Biomedical Research Institute (IMIB), Regional Campus of International Excellence \u201cCampus Mare Nostrum\u201d, Faculty of Medicine, University of Murcia, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2400-9213","authenticated-orcid":false,"given":"Jose Miguel","family":"Bolar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Legal and Forensic Medicine, Biomedical Research Institute (IMIB), Regional Campus of International Excellence \u201cCampus Mare Nostrum\u201d, Faculty of Medicine, University of Murcia, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Antonio","family":"Campillo","sequence":"additional","affiliation":[{"name":"Immunology Service, Instituto Murciano de Investigaci\u00f3n biosanitaria (IMIB), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-6372","authenticated-orcid":false,"given":"Mar\u00eda R.","family":"Moya-Quiles","sequence":"additional","affiliation":[{"name":"Immunology Service, Instituto Murciano de Investigaci\u00f3n biosanitaria (IMIB), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Miras","sequence":"additional","affiliation":[{"name":"Digestive Medicine Service, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9987-0994","authenticated-orcid":false,"given":"Manuel","family":"Muro","sequence":"additional","affiliation":[{"name":"Immunology Service, Instituto Murciano de Investigaci\u00f3n biosanitaria (IMIB), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-5893","authenticated-orcid":false,"given":"Alfredo","family":"Minguela","sequence":"additional","affiliation":[{"name":"Immunology Service, Instituto Murciano de Investigaci\u00f3n biosanitaria (IMIB), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda R.","family":"\u00c1lvarez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Immunology Service, Instituto Murciano de Investigaci\u00f3n biosanitaria (IMIB), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.jceh.2017.10.003","article-title":"Acute and Chronic Rejection After Liver Transplantation: What A Clinician Needs to Know","volume":"7","author":"Choudhary","year":"2017","journal-title":"J. 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