title: Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.
abstract: Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ETAR) and the angiotensin II receptor type 1 (AT1R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ETAR and anti-AT1R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient.
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padua University Hospital, Padova, Italy.|Consorzio per la Ricerca Sanitaria - CORIS (Consortium for Health Research), Padova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cozzi
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padua University Hospital, Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Calabrese
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padua University Hospital, Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Schiavon
authors.affiliation: Department of Anesthesiology and Intensive Care, Padua University Hospital, Padova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Feltracco
authors.affiliation: Consorzio per la Ricerca Sanitaria - CORIS (Consortium for Health Research), Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Seveso
authors.affiliation: Department of Anesthesiology and Intensive Care, Padua University Hospital, Padova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Carollo
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padua University Hospital, Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Loy
authors.affiliation: Transplant Immunology and Blood Bank, Maggiore Policlinico Hospital, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cardillo
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Transplant Immunology Unit, Padua University Hospital, Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rea
mesh_terms: D000328:Adult; D003550:Cystic Fibrosis / Q000601:surgery*; D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D011183:Postoperative Complications; D011379:Prognosis; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D044022:Receptor, Endothelin A / Q000276:immunology*; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: C544065:AGTR1 protein, human; D006680:HLA Antigens; D007518:Isoantibodies; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A
keywords: alloantibody; clinical research/practice; histocompatibility; immunobiology; lung transplantation/pulmonology; rejection: antibody-mediated (ABMR)