title: Acute cellular rejection is associated with matrix metalloproteinase-2 genotype chimerism after orthotopic liver transplantation.
abstract: OBJECTIVE
  Chimerism in transplantation medicine refers to the coexistence of cells of donor and recipient origin. Their existence in relation to possible pathological mechanisms remains largely unknown. We used donor-recipient mismatches for matrix metalloproteinases (MMP) gene polymorphisms in liver biopsies and in blood as a marker for chimerism after orthotopic liver transplantation (OLT). The second aim of this study was to evaluate these polymorphisms in relation to clinical outcome such as ischemia-reperfusion injury (IRI) and acute cellular rejection (ACR).
  
  
  METHODS
  MMP-2 and MMP-9 promoter polymorphism donor-recipient mismatches were determined in 147 OLT patients. The relationship between these MMP polymorphism mismatches in donor and recipient DNA with the development of IRI and ACR after OLT was evaluated. Liver biopsy specimens and peripheral blood samples were subsequently evaluated for the presence of chimerism, also in relation to these complications.
  
  
  RESULTS
  MMP polymorphism donor-recipient mismatches were found in 53.7% (MMP-2) and 35.5% (MMP-9) of the OLT patients but no relation was observed with IRI or ACR. Chimerism in liver biopsy specimens was found to be present in 28.8% (MMP-2) and 16.2% (MMP-9) of the cases. Liver chimerism in MMP-2 was found to be significantly associated with ACR after OLT (χ(2) 6.4, P = .01). Multivariate analysis revealed MMP-2 chimerism to be an independent risk factor for ACR after OLT even adjusted for Model for End-stage Liver Disease score (hazard ratio = 3.83, P = .03). In addition, evidence of donor chimerism was found in peripheral blood samples of the recipients in some cases.
  
  
  CONCLUSIONS
  Chimerism after OLT can be found in liver biopsy specimens and in peripheral blood. MMP donor-recipient polymorphism mismatches are good markers for assessing chimerism after OLT. In the multivariate analysis, liver chimerism in MMP-2 was found to be significantly associated with the development of ACR after OLT.
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: K S
authors.initials: KS
authors.lastname: Korkmaz
authors.forename: W R
authors.initials: WR
authors.lastname: Ten Hove
authors.forename: B-J F
authors.initials: BJ
authors.lastname: de Rooij
authors.forename: B
authors.initials: B
authors.lastname: van Hoek
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Reijden
authors.forename: M J
authors.initials: MJ
authors.lastname: Coenraad
authors.forename: J
authors.initials: J
authors.lastname: Dubbeld
authors.forename: H W
authors.initials: HW
authors.lastname: Verspaget
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D016009:Chi-Square Distribution; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D018183:Transplantation Chimera; D055815:Young Adult
chemical_list: C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9