title: Immune Complex-Type Deposits in the Fischer-344 to Lewis Rat Model of Renal Transplantation and a Subset of Human Transplant Glomerulopathy.
abstract: Antibody-mediated rejection is a leading cause for renal transplant loss. Rodent models are useful to dissect pathomechanisms and to develop treatment strategies. Although used for decades as a model, glomerular histopathological findings of Fischer-344 kidneys transplanted into Lewis rats have never been comprehensively described.
  
  
  
  Kidneys from Fischer-344 rats were transplanted into Lewis rats as life-sustaining allografts without immunosuppression. Lewis isografts and normal Fischer-344 kidneys served as controls. Grafts were harvested at 9 days, 6 and 26 weeks. Histopathological examination included light microscopy, immunohistochemistry, and morphometry. Findings were compared with 51 human biopsies with transplant glomerulopathy.
  
  
  
  Most glomerular findings in rat allografts resembled human acute and chronic antibody-mediated rejection with glomerulitis, microthrombosis, microaneurysms, glomerular hypertrophy, podocyte loss, glomerular basement membrane splitting, and secondary focal and segmental glomerulosclerosis. In line with previous reports on nonendothelial antigens, glomerular immunoglobulin and C4d deposition was mostly nonendothelial. Only in 26-week allografts, we found mesangial and subendothelial immune complex-type electron-dense deposits. Similar deposits were found in 8 of 51 human biopsies with transplant glomerulopathy after rigorous exclusion of immune complexes of other cause, particularly recurrent glomerulonephritis and hepatitis C.
  
  
  
  Thus, our model closely reflects the glomerular changes of acute antibody-mediated rejection in humans and of a special subset of human transplant glomerulopathy. The significance of alloimmune immune complex-type deposits in human transplants deserves further investigation.
authors.affiliation: 1 Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Giessen, Germany. 2 Institute of Pathology, University Hospital of Cologne, Cologne, Germany. 3 Institute of Transfusion Medicine, Hannover Medical School, Hannover, Germany. 4 Institute of Pathology, Department of Nephropathology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. 5 Institute of Pathology, Hannover Medical School, Hannover, Germany. 6 PATHOCOM, Rheine, Germany. 7 Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Giessen, Germany. 8 Medical Clinic III, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 9 Department of General, Visceral and Cancer Surgery, Transplant Center Cologne, University of Cologne, Cologne, Germany. 10 Imperial College Kidney and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. 11 Department of Cellular Pathology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Veronika
authors.initials: V
authors.lastname: Grau
authors.forename: Philip
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authors.lastname: Zeuschner
authors.forename: Stephan
authors.initials: S
authors.lastname: Immenschuh
authors.forename: Clemens Luitpold
authors.initials: CL
authors.lastname: Bockmeyer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Zell
authors.forename: Juliane
authors.initials: J
authors.lastname: Wittig
authors.forename: Karen
authors.initials: K
authors.lastname: Säuberlich
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abbas
authors.forename: Winfried
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authors.lastname: Padberg
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.forename: Melanie
authors.initials: M
authors.lastname: von Brandenstein
authors.forename: Monika
authors.initials: M
authors.lastname: Schlosser
authors.forename: Georg
authors.initials: G
authors.lastname: Dieplinger
authors.forename: Jack
authors.initials: J
authors.lastname: Galliford
authors.forename: Candice
authors.initials: C
authors.lastname: Clarke
authors.forename: Candice
authors.initials: C
authors.lastname: Roufosse
authors.forename: Jan Ulrich
authors.initials: JU
authors.lastname: Becker
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex; D001706:Biopsy; D002196:Capillaries; D015935:Complement C4b / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005920:Glomerular Mesangium / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology*; D007678:Kidney Glomerulus / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013927:Thrombosis / Q000473:pathology; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d