title: Rat renal transplant model for mixed acute humoral and cellular rejection: Weak correlation of serum cytokines/chemokines with intragraft changes.
abstract: BACKGROUND
  Acute renal allograft rejection remains a major cause of allograft dysfunction; especially for episodes with mixed humoral and cellular character which can be detrimental for graft survival. We established a rat RT model with exclusive and complete MHC-disparity to investigate pathomechanisms of acute rejection and evaluate serum multiplex assays as a diagnostic tool in this context.
  
  
  METHODS
  LEW rats receive congeneic LEW.1W allografts (allo), no immunosuppression. Planned duration of the experiment was 4 weeks (n = 13 allo, n = 3 iso). To study kinetics of rejection, additional animals were sacrificed at day 7 (n = 6 allo and n = 3 iso) and day 21 (n = 3 allo). Serum cytokines and chemokine were longitudinally analyzed with multiplex assays in n = 5 allo and n = 5 controls. Allografts were assessed by histopathology, immunohisto-chemistry and PCR.
  
  
  RESULTS
  Animals develop allograft dysfunction acute humoral rejection with additional cellular components. Donor-specific MHC-antibodies are already detectable at day seven (d7) after RT. Leukocytic graft infiltrates are dominated by macrophages and additionally consist of T-cells, B-cells and NK-cells. Increased intragraft expression of interleukin-2, interferon gamma, tumor necrosis factor alpha as well as B-cell activating factor and its receptor are observed. Of the 24 serum cytokines/chemokines, only CCL2 is significantly different (higher)in allo vs. controls at d7 (p = 0.02).
  
  
  CONCLUSIONS
  Correlation of serum chemokines/cytokines with features of humoral and cellular rejection, as reproduced in our LEW.1W to LEW rat renal transplant model, is limited. Macrophages, B-cells and their signaling pathways deserve more attention in genesis and possibly also treatment of acute rejection.
authors: Department of Hepatobilary and Transplant Surgery and Pediatric Nephrology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; University Childrens Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: lemke_anja@gmx.de.
authors: Anja
authors: A
authors: Lemke
authors: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: m.noriega@uke.de.
authors: Mercedes
authors: M
authors: Noriega
authors: Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: anjaroeske@live.com.
authors: Anja M
authors: AM
authors: Röske
authors: University Childrens Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: kemper@uke.de.
authors: Markus J
authors: MJ
authors: Kemper
authors: Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: nashan@uke.de.
authors: Björn
authors: B
authors: Nashan
authors: Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany; Deutsches Zentrum für Infektionsforschung DZIF, Heidelberg, Germany. Electronic address: Falk.Christine@mh-hannover.de.
authors: Christine S
authors: CS
authors: Falk
authors: Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: martina.koch@uke.de.
authors: Martina
authors: M
authors: Koch
mesh_terms: D064591:Allografts / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007518:Isoantibodies / Q000378:metabolism*; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D016207:Cytokines; D006649:Histocompatibility Antigens; D007518:Isoantibodies
keywords: B-cells; MHC disparity; Macrophages; Mixed acute rejection