title: Immunoglobulin G profile in hyperacute rejection after multivisceral xenotransplantation.
abstract: BACKGROUND
  Xenotransplantation is a potential solution for the high mortality of patients on the waiting list for multivisceral transplantation; nevertheless, hyperacute rejection (HAR) hampers this practice and motivates innovative research. In this report, we describe a model of multivisceral xenotransplantation in which we observed immunoglobulin G (IgG) involvement in HAR.
  
  
  METHODS
  We recovered en bloc multivisceral grafts (distal esophagus, stomach, small intestine, colon, liver, pancreas, and kidneys) from rabbits (n = 20) and implanted them in the swine (n = 15) or rabbits (n = 5, control). Three hours after graft reperfusion, we collected samples from all graft organs for histological study and to assess IgG fixation by immunofluorescence. Histopathologic findings were graded according to previously described methods.
  
  
  RESULTS
  No histopathological features of rejection were seen in the rabbit allografts. In the swine-to-rabbit grafts, features of HAR were moderate in the liver and severe in esophagus, stomach, intestines, spleen, pancreas, and kidney. Xenograft vessels were the central target of HAR. The main lesions included edema, hemorrhage, thrombosis, myosites, fibrinoid degeneration, and necrosis. IgG deposition was intense on cell membranes, mainly in the vascular endothelium.
  
  
  CONCLUSIONS
  Rabbit-to-swine multivisceral xenotransplants undergo moderate HAR in the liver and severe HAR in the other organs. Moderate HAR in the liver suggests a degree of resistance to the humoral immune response in this organ. Strong IgG fixation in cell membranes, including vascular endothelium, confirms HAR characterized by a primary humoral immune response. This model allows appraisal of HAR in multiple organs and investigation of the liver's relative resistance to this immune response.
authors.affiliation: Department of Gastroenterology (LIM 37), University of São Paulo School of Medicine, Sao Paulo, Brazil. fgalvao@usp.br
authors.forename: Flavio H F
authors.initials: FH
authors.lastname: Galvao
authors.forename: Wangles
authors.initials: W
authors.lastname: Soler
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pompeu
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Waisberg
authors.forename: Evandro S D
authors.initials: ES
authors.lastname: Mello
authors.forename: Anderson C L
authors.initials: AC
authors.lastname: Costa
authors.forename: Walcy
authors.initials: W
authors.lastname: Teodoro
authors.forename: Ana P
authors.initials: AP
authors.lastname: Velosa
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Leila
authors.initials: L
authors.lastname: Antonangelo
authors.forename: Sergio
authors.initials: S
authors.lastname: Catanozi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martins
authors.forename: Luiz M S
authors.initials: LM
authors.lastname: Malbouisson
authors.forename: Ruy J
authors.initials: RJ
authors.lastname: Cruz
authors.forename: Estela R
authors.initials: ER
authors.lastname: Figueira
authors.forename: Joel A R
authors.initials: JA
authors.lastname: Filho
authors.forename: Eleazar
authors.initials: E
authors.lastname: Chaib
authors.forename: Luiz A C
authors.initials: LA
authors.lastname: D'Albuquerque
mesh_terms: D000208:Acute Disease; D000818:Animals; D004064:Digestive System / Q000276:immunology / Q000473:pathology; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000378:metabolism*; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology / Q000473:pathology; D008297:Male; D023421:Models, Animal; D009928:Organ Specificity; D011817:Rabbits; D034421:Sus scrofa; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G