title: The impact of non-HLA antibodies directed against endothelin-1 type A receptors (ETAR) on early renal transplant outcomes.
abstract: BACKGROUND
  Non-HLA antibodies (Abs) targeting vascular receptors are considered to have an influence on renal transplant injury. Anti-endothelin-1 type A receptor (anti-ETAR) antibodies were associated with cellular and antibody-mediated rejection and early onset of vasculopathy in heart transplant patients but their role in renal transplantation remains unclear. The aim of our study was to assess the incidence and importance of anti-ETAR antibodies and their impact on renal transplant during the first year observation.
  
  
  METHODS
  We evaluated the presence of anti-ETAR antibodies in 116 consecutive renal transplant recipients in pre- and post-transplant screening (before and in 1st, 3rd, 6th, 12th month after transplantation). Additionally, we assessed the presence of anti-HLA antibodies. Anti-ETAR antibodies were assayed by ELISA. The diagnosis of acute rejection was based on the Banff criteria.
  
  
  RESULTS
  Anti-ETAR antibodies were observed in 55 (47.4%) of the analyzed recipients before transplantation. The function of renal transplant was significantly worse in the anti-ETAR(+) group compared to the anti-ETAR(-) group during the first post-transplant year. One month after transplantation the serum creatinine in anti-ETAR (+) patients (pts) was 1.86±0.8mg/dl and 1.51±0.5 in anti-ETAR(-) pts (p=0.009). Twelve months after transplantation the difference between the groups was still observed 1.70±0.7 vs. 1.40±0.4 (p=0.04). Biopsy proven acute rejection was recognized in 8/55 (14.5%) in ETAR(+) and 9/61 (14.8%) in ETAR(-) patients but cases with mild to severe intimal arteritis (v1-v3) were more often observed in patients with the presence of anti-ETAR Abs 4/55 (7.2%) comparing with 1/61 (1.6%) in anti-ETAR(-) patients. The anti-ETAR antibody levels varied at different measurement intervals during the one-year follow-up.
  
  
  CONCLUSIONS
  The presence of anti-ETAR antibodies is associated with a worse renal transplant function during the first 12months after transplantation. Including anti-ETAR antibodies in the diagnostics of renal transplant recipient immune status should be considered to provide comprehensive assessment of humoral alloimmunity.
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland. Electronic address: m.banasik@interia.pl.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Banasik
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Boratyńska
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kościelska-Kasprzak
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Krajewska
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Oktawia
authors.initials: O
authors.lastname: Mazanowska
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kamińska
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Bartoszek
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Marcelina
authors.initials: M
authors.lastname: Zabińska
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Myszka
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Nowakowska
authors.affiliation: Department of Pathomorphology, Wroclaw Medical University, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Hałoń
authors.affiliation: Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dawiskiba
authors.affiliation: Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Chudoba
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland.
authors.forename: Marian
authors.initials: M
authors.lastname: Klinger
mesh_terms: D000208:Acute Disease; D000328:Adult; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000276:immunology*; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044022:Receptor, Endothelin A / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies; D044022:Receptor, Endothelin A; D003404:Creatinine
keywords: Antibody mediated rejection; ETAR Abs; Humoral rejection; Non-HLA antibodies; Renal transplant injury; Renal transplantation