title: Non-HLA Antibodies May Accelerate Immune Responses After Intestinal and Multivisceral Transplantation.
abstract: BACKGROUND
  Non-HLA alloantibodies and autoantibodies are involved in allograft rejection in kidney and heart transplantation. Their role in intestinal transplantation has not yet been described. We examined the development of antiangiotensin II type I receptor antibodies (anti-AT1R) and antiendothelin type A receptor antibodies associated with the clinical course and histopathological findings of intestinal transplantation recipients.
  
  
  METHODS
  Thirty-seven patients underwent intestinal or multivisceral transplantation. Non-HLA antibodies (non-HLAabs) were screened in 29 transplant recipients. Antibody-levels greater than 12 U/L were considered positive and were evaluated retrospectively regarding rejection episodes.
  
  
  RESULTS
  Twenty patients developed anti-AT1R and/or antiendothelin type A receptor antibodies (non-HLAabs group), 9 did not (control group). The non-HLAabs group had a higher rate of allograft rejection than controls (80% vs 55%), especially a higher rate of antibody-mediated rejections (55% vs 11%, P < 0.01) with detection of donor-specific anti-HLAabs. All rejection episodes in the non-HLAabs group appeared around the time of positive non-HLAabs detection. Five patients had acute cellular rejections at the time of non-HLAabs development, 4 had viral infections.
  
  
  CONCLUSIONS
  Our data suggest that antibody-mediated mechanisms targeting antigens beyond HLA may trigger and accelerate immune responses. Given the possibility of pharmacologic targeting of non-HLA receptors, future studies will focus on the explanation of mechanisms how non-HLAabs may enhance rejection and affect long-term allograft survival.
authors: 1 Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. 2 Institute for Transfusion Medicine and HLA Typing Laboratory, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. 3 Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. 4 Department for Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors: Undine Ariane
authors: UA
authors: Gerlach
authors: Nils
authors: N
authors: Lachmann
authors: Giuseppina
authors: G
authors: Ranucci
authors: Birgit
authors: B
authors: Sawitzki
authors: Constanze
authors: C
authors: Schoenemann
authors: Johann
authors: J
authors: Pratschke
authors: Duska
authors: D
authors: Dragun
authors: Andreas
authors: A
authors: Pascher
mesh_terms: D000208:Acute Disease; D000328:Adult; D064591:Allografts; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005858:Germany; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D056724:Immunity, Humoral; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007422:Intestines / Q000276:immunology / Q000637:transplantation* / Q000821:virology; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D044022:Receptor, Endothelin A / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome; D014777:Virus Diseases / Q000276:immunology; D014781:Viscera / Q000276:immunology / Q000637:transplantation*; D055815:Young Adult
chemical_list: C544065:AGTR1 protein, human; D001323:Autoantibodies; D015415:Biomarkers; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A