Profiling non-HLA antibody responses in antibody-mediated rejection following heart transplantation.
B cell biology
alloantibody
autoantibody
autoantigen
basic (laboratory) research/science
heart transplantation/cardiology
immunobiology
rejection: antibody-mediated (ABMR)
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
04
10
2019
revised:
24
02
2020
accepted:
11
03
2020
pubmed:
20
3
2020
medline:
22
6
2021
entrez:
20
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32190967
doi: 10.1111/ajt.15871
pmc: PMC8117249
mid: NIHMS1698448
pii: S1600-6135(22)22575-1
doi:
Substances chimiques
HLA Antigens
0
Isoantibodies
0
Vimentin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2571-2580Subventions
Organisme : NCRR NIH HHS
ID : S10 RR027050
Pays : United States
Organisme : NIH HHS
ID : S10RR027050
Pays : United States
Organisme : NIH HHS
ID : T32-HL-007854-21
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007854
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116814
Pays : United States
Organisme : NIH HHS
ID : R01-AI116814
Pays : United States
Informations de copyright
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
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