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Extended haplotypes at the complement factor H gene locus are associated with liver transplant rejection.

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Τίτλος: Extended haplotypes at the complement factor H gene locus are associated with liver transplant rejection.
Συγγραφείς: Nieuwenhuis LM; Department of Surgery, Section of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Loza BL; Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Berger SP; Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Jansen BH; Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Blokzijl H; Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Daha MR; Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Department of Nephrology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands., Lammerts RGM; Transplantation Immunology, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Shaked A; Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Asrani S; Baylor University Medical Center, Dallas, Texas, USA., Lisman T; Department of Surgery, Section of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Weersma RK; Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Festen EAM; Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., de Meijer VE; Department of Surgery, Section of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Poppelaars F; Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Συλλογικό Έργο: TransplantLines Investigators
Πηγή: Hepatology communications [Hepatol Commun] 2026 Jul 15; Vol. 10 (8). Date of Electronic Publication: 2026 Jul 15 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 101695860 Publication Model: eCollection Cited Medium: Internet ISSN: 2471-254X (Electronic) Linking ISSN: 2471254X NLM ISO Abbreviation: Hepatol Commun Subsets: MEDLINE
Imprint Name(s): Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc.
Original Publication: [Hoboken, NJ] : Wiley Periodicals, Inc. on behalf of the American Association for the Study of Liver Diseases, [2017]-
Ιατρικοί όροι (MeSH): Liver Transplantation*/adverse effects , Graft Rejection*/genetics , Graft Rejection*/immunology , Complement Factor H*/genetics , Complement C3b Inactivator Proteins*/genetics, Haplotypes ; Humans ; Male ; Female ; Kaplan-Meier Estimate ; Blood Proteins
Περίληψη: Background: Acute T-cell-mediated rejection (ACR) remains an important complication after liver transplantation. Polymorphisms in the factor H gene (CFH) and factor H-related protein genes (CFHRs) affect the risk of multiple complement-related diseases. Given the complement system's key role in alloimmunity, we hypothesized that variants in CFH and CFHRs associate with ACR risk after liver transplantation.
Methods: In 689 donor-recipient pairs, the deletion of CFHR1 and CFHR3 (CFHR3,1Δ), a low-expression variant of CFHR2, and CFH haplotypes were extracted from both donor and recipient genotypes following appropriate imputation and quality control steps.
Results: Kaplan-Meier survival curves and multivariable Cox regression analysis showed increased ACR incidence after transplantation of donor livers carrying 2 copies of the CFHR3,1Δ (log-rank p=0.03, HR: 2.76, 95% CI: 1.18-6.45) or the related CFH-H4a haplotype (log-rank p=0.03, HR: 1.65, 95% CI: 1.04-2.63). In contrast, a lower ACR incidence was observed after transplanting donor livers with a low-expressing CFHR2 variant (log-rank p=0.04, HR: 0.66, 95% CI: 0.45-0.96) or the related CFH-H2 haplotype (log-rank p=0.01, HR: 0.58, 95% CI: 0.37-0.92). When analyzing recipient genotypes, only CFHR3,1Δ was associated with ACR (log-rank: p=0.01, HR: 2.55, 95% CI: 1.15-5.65).
Conclusions: Common functional variants in the CFH-CFHR region are associated with rejection risk after liver transplantation, highlighting a previously overlooked relevance of the complement system in liver transplantation.
(Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, LLC. on behalf of the American Association for the Study of Liver Diseases.)
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Contributed Indexing: Keywords: acute cellular rejection; genetics; immunology; liver disease; liver transplantation
Substance Nomenclature: 80295-65-4 (Complement Factor H)
0 (Complement C3b Inactivator Proteins)
0 (CFHR3 protein, human)
0 (CFHR1 protein, human)
0 (Blood Proteins)
Entry Date(s): Date Created: 20260722 Date Completed: 20260722 Latest Revision: 20261028
Update Code: 20261029
PubMed Central ID: PMC13671603
DOI: 10.1097/HC9.0000000000000997
PMID: 42486812
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2471-254X
DOI:10.1097/HC9.0000000000000997