Antibodies to Vascular Autoantigens Are Associated with Poor Long-Term Survival of Liver Re-Transplant

Q. Xu¹, V. C. McAlister², S. Leckie², A. A. House², A. Zeevi¹

¹Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, ²Multiorgan Transplant Program, London Health Sciences Centre, London, ON, Canada

Meeting: 2020 American Transplant Congress

Abstract number: 372

Keywords: Antibodies, Autoimmunity, Graft survival, Liver transplantation

Session Information

Session Name: Liver Retransplantation and Other Complications

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

Presentation Time: 3:51pm-4:03pm

Location: Virtual

*Purpose: Autoantibodies, which may be generated in transplantation through the exposure of cryptic antigens, are reported to be detrimental for allograft survival. We have demonstrated that pre-formed Angiotensin II Type I Receptor agonistic autoantibodies (AT1R-AA) are associated with poor allograft survival in liver retransplantation. Here we examine the effect of other pre-formed autoantibodies on graft survival after liver retransplantation.

*Methods: We studied a single-center retrospective cohort of 93 patients (1991-2018) who received second liver transplant. Pre-retransplant sera were tested with Luminex-based solid-phase assays for antibodies to 33 autoantigens. The primary outcome is survival of the second liver graft.

*Results: With follow-up for up to 25 years, 48/93 (51.6%) patients had lost second liver transplants. Seven autoantibodies were found to be significantly higher (p<0.05) in patients who lost grafts vs. whose grafts were still functioning. In univariate Cox regression, autoantibodies to LG3, a C-terminal fragment of Perlecan [HR=2.472 (1.376-4.44), p=0.002], Agrin [HR=1.83 (1.023-3.271), p=0.042], and Chromatin assembly factor 1 subunit B [HR=2.356 (1.053-5.275), p=0.037] were found to be associated with poor graft survival. In the multivariate model adjusting age and gender, LG3 autoantibody [HR=2.345 (1.105-4.980), p=0.027] and AT1R-AA [2.091 (1.066- 4.098), p=0.032] were significant and independent contributors for graft loss. 22/93 patients (23.4%) had positive autoantibodies to LG3, of which 18 (81.8%) had lost their grafts. In Kaplan-Meier analysis (Figure 1), patients with positive autoantibodies to LG3 had significantly worse graft survival (p=0.002) than those with negative LG3 autoantibodies.

*Conclusions: Autoantibodies to either LG3 or AT1R were found to be associated with inferior long-term outcomes of a second liver transplant. AT1R-AA causes vasoconstriction. Autoantibodies to LG3 are not yet defined as agonistic or antagonistic but have been shown to aggravate the ischemia-reperfusion injury and vascular rejection in kidney transplants. The detrimental effect of autoantibodies after transplantation may be mediated through their effect on graft and host vasculature.

To cite this abstract in AMA style:

Xu Q, McAlister VC, Leckie S, House AA, Zeevi A. Antibodies to Vascular Autoantigens Are Associated with Poor Long-Term Survival of Liver Re-Transplant [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/antibodies-to-vascular-autoantigens-are-associated-with-poor-long-term-survival-of-liver-re-transplant/. Accessed May 13, 2025.

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