Development of Non-Human Leukocyte Antigen Antibodies in Cardiac Antibody-Mediated Rejection

S. B. See¹, B. S. Mantell², K. J. Clerkin³, B. Ray⁴, E. R. Vasilescu⁵, C. Marboe⁵, Y. Naka⁶, S. Restaino¹, P. C. Colombo³, L. J. Addonizio², M. A. Farr³, E. Zorn¹

¹Columbia Center for Translational Immunology, Columbia University, New York, NY, ²Department of Pediatrics, Columbia University, New York, NY, ³Division of Cardiology, Columbia University, New York, NY, ⁴Immucor, Georgia, GA, ⁵Department of Pathology and Cell Biology, Columbia University, New York, NY, ⁶Department of Surgery, Columbia University, New York, NY

Meeting: 2019 American Transplant Congress

Abstract number: A44

Keywords: Antibodies, Autoimmunity, Heart, Rejection

Session Information

Session Name: Poster Session A: B-cell / Antibody /Autoimmunity

Session Type: Poster Session

Date: Saturday, June 1, 2019

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: Antibody-mediated rejection (AMR), mainly driven by the development of donor-specific antibodies (DSA) directed against mismatched donor class I and class II HLA, is a major risk factor for graft loss in cardiac transplantation. In recent years, the relevance of non-HLA antibodies has become more prominent, particularly as antibody-mediated rejection can be diagnosed in the absence of DSA

*Methods: Here, we assessed a cohort of 64 orthotopic heart transplant recipients transplanted at NewYork-Presbyterian Hospital/Columbia University Medical Center between 1998 and 2014. Serum collected at the time of endomyocardial biopsy from 43 patients with AMR (≥pAMR1) and 21 control patients without AMR were tested for serum reactivity to a panel of 44 non-HLA autoantigens by Immucor.

*Results: The AMR group had a significantly greater percentage of patients with serum positivity (>MFI 1000) to panel autoantigens compared to AMR-negative controls (p=0.0009) and to a healthy control group of 94 non-transfused males (p<0.0001). Moreover, DSA-positive AMR patients exhibited greater reactivity to autoantigens compared to DSA-negative AMR patients (p=0.0098). This difference was driven by statistically significant increases in reactivity against 16 of the 44 autoantigens tested.

*Conclusions: These results suggest that antibodies to non-HLA are associated with DSA-positive AMR although their role in mediating allograft injury is not known. Furthermore, non-HLA autoantibodies do not appear to contribute to DSA-negative AMR.

To cite this abstract in AMA style:

See SB, Mantell BS, Clerkin KJ, Ray B, Vasilescu ER, Marboe C, Naka Y, Restaino S, Colombo PC, Addonizio LJ, Farr MA, Zorn E. Development of Non-Human Leukocyte Antigen Antibodies in Cardiac Antibody-Mediated Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/development-of-non-human-leukocyte-antigen-antibodies-in-cardiac-antibody-mediated-rejection/. Accessed May 30, 2025.

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