PMID- 32190967 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20230124 IS - 1600-6143 (Electronic) IS - 1600-6135 (Print) IS - 1600-6135 (Linking) VI - 20 IP - 9 DP - 2020 Sep TI - Profiling non-HLA antibody responses in antibody-mediated rejection following heart transplantation. PG - 2571-2580 LID - 10.1111/ajt.15871 [doi] AB - Antibody-mediated rejection (AMR) driven by the development of donor-specific antibodies (DSA) directed against mismatched donor human leukocyte antigen (HLA) is a major risk factor for graft loss in cardiac transplantation. Recently, the relevance of non-HLA antibodies has become more prominent as AMR can be diagnosed in the absence of circulating DSA. Here, we assessed a single-center cohort of 64 orthotopic heart transplant recipients transplanted between 1994 and 2014. Serum collected from patients with >/= pAMR1 (n = 43) and non-AMR (n = 21) were tested for reactivity against a panel of 44 non-HLA autoantigens. The AMR group had a significantly greater percentage of patients with elevated reactivity to autoantigens compared to non-AMR (P = .002) and healthy controls (n = 94, P < .0001). DSA-positive AMR patients exhibited greater reactivity to autoantigens compared to DSA-negative (P < .0001) and AMR patients with DSA and PRA > 10% were identified as the subgroup with significantly elevated responses. Reactivity to 4 antigens, vimentin, beta-tubulin, lamin A/C, and apolipoprotein L2, was significantly different between AMR and non-AMR patients. Moreover, increased reactivity to these antigens was associated with graft failure. These results suggest that antibodies to non-HLA are associated with DSA-positive AMR although their specific role in mediating allograft injury is not yet understood. CI - (c) 2020 The American Society of Transplantation and the American Society of Transplant Surgeons. FAU - See, Sarah B AU - See SB AUID- ORCID: 0000-0002-4208-317X AD - Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Mantell, Benjamin S AU - Mantell BS AD - Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, New York, USA. AD - Department of Pediatrics, Division of Pediatric Cardiology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Clerkin, Kevin J AU - Clerkin KJ AD - Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Ray, Bryan AU - Ray B AD - Immucor, Inc., Waukesha, Wisconsin, USA. FAU - Vasilescu, E Rodica AU - Vasilescu ER AD - Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Marboe, Charles C AU - Marboe CC AD - Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Naka, Yoshifumi AU - Naka Y AD - Department of Surgery, Division of Cardiothoracic Surgery, Columbia University Irving Medical Center, New York, New York, USA. FAU - Restaino, Susan AU - Restaino S AD - Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Colombo, Paolo C AU - Colombo PC AD - Department of Pediatrics, Division of Pediatric Cardiology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Addonizio, Linda J AU - Addonizio LJ AD - Department of Pediatrics, Division of Pediatric Cardiology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Farr, Maryjane A AU - Farr MA AD - Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA. FAU - Zorn, Emmanuel AU - Zorn E AUID- ORCID: 0000-0001-9985-8389 AD - Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, New York, USA. LA - eng GR - S10 RR027050/RR/NCRR NIH HHS/United States GR - S10RR027050/NH/NIH HHS/United States GR - T32-HL-007854-21/NH/NIH HHS/United States GR - T32 HL007854/HL/NHLBI NIH HHS/United States GR - R01 AI116814/AI/NIAID NIH HHS/United States GR - R01-AI116814/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200426 PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 RN - 0 (HLA Antigens) RN - 0 (Isoantibodies) RN - 0 (Vimentin) SB - IM MH - *Antibody Formation MH - Graft Rejection/etiology MH - HLA Antigens MH - *Heart Transplantation/adverse effects MH - Humans MH - Isoantibodies MH - Tissue Donors MH - Vimentin PMC - PMC8117249 MID - NIHMS1698448 OTO - NOTNLM OT - B cell biology OT - alloantibody OT - autoantibody OT - autoantigen OT - basic (laboratory) research/science OT - heart transplantation/cardiology OT - immunobiology OT - rejection: antibody-mediated (ABMR) COIS- Disclosures The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation: BR is an employee of Immucor, Inc. None of the other authors have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose. EDAT- 2020/03/20 06:00 MHDA- 2021/06/22 06:00 PMCR- 2021/05/13 CRDT- 2020/03/20 06:00 PHST- 2019/10/04 00:00 [received] PHST- 2020/02/24 00:00 [revised] PHST- 2020/03/11 00:00 [accepted] PHST- 2020/03/20 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/03/20 06:00 [entrez] PHST- 2021/05/13 00:00 [pmc-release] AID - S1600-6135(22)22575-1 [pii] AID - 10.1111/ajt.15871 [doi] PST - ppublish SO - Am J Transplant. 2020 Sep;20(9):2571-2580. doi: 10.1111/ajt.15871. Epub 2020 Apr 26.