{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:54:33Z","timestamp":1781499273460,"version":"3.54.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19-01311"],"award-info":[{"award-number":["PI19-01311"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While donor-specific antibodies against human leukocyte antigens (HLA-DSA) are recognized contributors to allograft injury, non-HLA antibodies are increasingly implicated in solid-organ transplant rejection. However, evidence in pediatric liver transplantation remains limited. We aimed to identify anti-HLA and non-HLA antibodies associated with liver fibrosis risk in long-term pediatric liver transplant recipients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This cross-sectional study included 75 pediatric liver recipients transplanted between 2006-2014 (median 13.8 years), 15 pediatric patients on liver-transplant waiting list and 22 healthy adult controls (HC). Serum samples were tested for non-HLA, anti-HLA class-I, class-II and anti-MHC class-I chain-related protein A (MICA) antibodies by multiplex microsphere-based flow cytometry (Luminex Technology). Liver fibrosis risk was assessed using the Fibrosis-4 (FIB-4) index. Univariate and multivariate logistic regression analyses evaluated associations between antibody positivity and FIB-4 index elevation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Liver-transplant patients showed significantly higher frequencies of eight non-HLA specificities compared to HC: C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CXCL11, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glial cell line-derived neurotrophic factor (GDNF), leucine-rich repeat transmembrane protein 2 (FLRT2), interferon gamma (IFNG) and vimentin (VM). Anti-HLA class-II antibody prevalence was significantly higher post-transplantation (44% vs. 0%, p=0.002). In multivariate analysis, anti-GDNF antibody positivity was independently associated with increased FIB-4 values (odds ratio [OR] 5.61, p=0.04), while female sex showed a protective effect (OR 0.23, p=0.02).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Eight non-HLA antibodies are prevalent in pediatric liver-transplant recipients and waitlisted candidates. Anti-GDNF antibodies were independently associated with higher FIB-4 values in long-term pediatric liver transplant recipients, suggesting a potential biomarker role in liver injury that requires validation in larger longitudinal cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1813802","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:25:28Z","timestamp":1781497528000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence of non-HLA antibodies and their association with FIB-4 index-based fibrosis risk in pediatric liver transplant recipients with long-term graft survival (&gt;10 years)"],"prefix":"10.3389","volume":"17","author":[{"given":"Ricardo","family":"Cuesta-Mart\u00edn de la C\u00e1mara","sequence":"first","affiliation":[{"name":"Clinical Immunology Department, University Hospital La Paz","place":["Madrid, 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Dolores","family":"Lled\u00edn-Barbacho","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology Department, University Hospital La Paz","place":["Madrid, Spain"]},{"name":"European Reference Network (ERN) RARE LIVER","place":["Madrid, Spain"]},{"name":"European Reference Network (ERN) TransplantChild","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Mancebo","sequence":"additional","affiliation":[{"name":"Immunology Department, University Hospital 12 de Octubre","place":["Madrid, Spain"]},{"name":"12 de Octubre Hospital Health Research Institute (imas12)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Castro-Panete","sequence":"additional","affiliation":[{"name":"Immunology Department, University Hospital 12 de Octubre","place":["Madrid, Spain"]},{"name":"12 de Octubre Hospital Health Research Institute (imas12)","place":["Madrid, 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