Profiling non-HLA antibody responses in antibody-mediated rejection following heart transplantation

Sarah B. See, Benjamin S. Mantell, Kevin J. Clerkin, Bryan Ray, E. Rodica Vasilescu, Charles C. Marboe, Yoshifumi Naka, Susan Restaino, Paolo C. Colombo, Linda J. Addonizio, Maryjane A. Farr, Emmanuel Zorn

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2571-2580
Number of pages10
JournalAmerican Journal of Transplantation
Volume20
Issue number9
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

Keywords

  • alloantibody
  • autoantibody
  • autoantigen
  • B cell biology
  • basic (laboratory) research/science
  • heart transplantation/cardiology
  • immunobiology
  • rejection: antibody-mediated (ABMR)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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