title: Complement C3F allotype synthesized by liver recipient modifies transplantation outcome independently from donor hepatic C3.
abstract: Complement component 3 (C3) presents both slow (C3S) and fast (C3F) variants, which can be locally produced and activated by immune system cells. We studied C3 recipient variants in 483 liver transplant patients by RT-PCR-HRM to determine their effect on graft outcome during the first year post-transplantation. Allograft survival was significantly decreased in C3FF recipients (C3SS 95% vs C3FS 91% vs C3FF 83%; P=.01) or C3F allele carriers (C3F absence 95% vs C3F presence 90%, P=.02). C3FF genotype or presence of C3F allele independently increased risk for allograft loss (OR: 2.38, P=.005 and OR: 2.66, P=.02, respectively). C3FF genotype was more frequent among patients whose first infection was of viral etiology (C3SS 13% vs C3FS 18% vs C3FF 32%; P=.04) and independently increased risk for post-transplant viral infections (OR: 3.60, P=.008). On the other hand, C3FF and C3F protected from rejection events (OR: 0.54, P=.03 and OR: 0.63, P=.047, respectively). Differences were not observed in hepatitis C virus recurrence or patient survival. In conclusion, we show that, independently from C3 variants produced by donor liver, C3F variant from recipient diminishes allograft survival, increases susceptibility to viral infections, and protects from rejection after transplantation. C3 genotyping of liver recipients may be useful to stratify risk.
authors: Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.
authors: Diana María
authors: DM
authors: Valero-Hervás
authors: Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.
authors: Elena
authors: E
authors: Sánchez-Zapardiel
authors: Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.|I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.
authors: María José
authors: MJ
authors: Castro
authors: Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.
authors: Fernando
authors: F
authors: Gallego-Bustos
authors: Department of General and Digestive Surgery and Abdominal Organ Transplantation, Hospital 12 de Octubre, Madrid, Spain.
authors: Félix
authors: F
authors: Cambra
authors: Department of General and Digestive Surgery and Abdominal Organ Transplantation, Hospital 12 de Octubre, Madrid, Spain.
authors: Iago
authors: I
authors: Justo
authors: Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.|I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.
authors: Rocío
authors: R
authors: Laguna-Goya
authors: I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.|Department of General and Digestive Surgery and Abdominal Organ Transplantation, Hospital 12 de Octubre, Madrid, Spain.|School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
authors: Carlos
authors: C
authors: Jiménez-Romero
authors: I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.|Department of General and Digestive Surgery and Abdominal Organ Transplantation, Hospital 12 de Octubre, Madrid, Spain.|School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
authors: Enrique
authors: E
authors: Moreno
authors: I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.|Unit of Infectious Diseases, Hospital 12 de Octubre, Madrid, Spain.
authors: Francisco
authors: F
authors: López-Medrano
authors: I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.|Unit of Infectious Diseases, Hospital 12 de Octubre, Madrid, Spain.
authors: Rafael
authors: R
authors: San Juan
authors: I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.|Unit of Infectious Diseases, Hospital 12 de Octubre, Madrid, Spain.
authors: Mario
authors: M
authors: Fernández-Ruiz
authors: I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.|School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.|Unit of Infectious Diseases, Hospital 12 de Octubre, Madrid, Spain.
authors: José María
authors: JM
authors: Aguado
authors: Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.|I+12 Research Institute, Hospital 12 de Octubre, Madrid, Spain.|School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.|Section of Immunology, Universidad San Pablo CEU, Madrid, Spain.
authors: Estela
authors: E
authors: Paz-Artal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003179:Complement C3b / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011183:Postoperative Complications; D011379:Prognosis; D020033:Protein Isoforms; D012307:Risk Factors; D014019:Tissue Donors; D066027:Transplant Recipients; D014184:Transplantation, Homologous; D014777:Virus Diseases / Q000209:etiology* / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms; C046821:complement C3f; D003179:Complement C3b
keywords: C3 complement component; complement system; graft rejection; graft survival; infection; liver transplantation