Isolated De Novo Antiendothelial Cell Antibodies and Kidney Transplant Rejection

Abstract

Background: Studies analyzing the role of antiendothelial cell antibodies (AECAs) in large series of kidney transplant recipients are scarce, and HLA, MHC (major histocompatibility complex) class I-related chain A (MICA), and angiotensin II type 1 receptor have not been formally excluded as targets.

Study design: Retrospective study of a cohort of kidney transplant recipients.

Setting & participants: 324 kidney transplant recipients who were negative for anti-HLA, anti-MICA, and anti-angiotensin II type 1 receptor antibodies were tested for AECAs in pre- and posttransplantation serum samples.

Predictors: AECA-positive (preformed [pre⁺/post⁺] vs de novo [pre^-/post⁺]) versus AECA-negative (pre^-/post^-) before or after transplantation.

Outcomes: Patient mortality, transplant loss, and acute rejection events.

Results: 66 (20%) patients were AECA positive (39 [12%] preformed, 27 [8%] de novo) and 258 (80%) were AECA negative. During a follow-up of 10 years, 7 (18%) AECA pre⁺/post⁺ patients had rejections compared with 14 (52%) AECA pre^-/post⁺ and 57 (22%) AECA pre^-/post^- recipients (OR, 3.80; P=0.001). AECA pre^-/post⁺ status emerged as an independent risk factor for transplant rejection compared to the AECA pre^-/post^- group (OR, 5.17; P<0.001). However, AECA pre⁺/post⁺ and AECA pre^-/post⁺ patients did not show higher risk for either patient death (ORs of 1.49 [P=0.7] and 1.06 [P=0.9], respectively) or transplant loss (ORs of 1.22 and 0.86, respectively; P for both = 0.8) compared to the AECA pre^-/post^- population.

Limitations: Retrospective study. Posttransplantation sera were collected before or after rejection, entailing a nearly cross-sectional relationship between the exposure and outcome. Lack of identification of precise antigens for AECAs.

Conclusions: De novo AECAs may be associated with rejection. These antibodies might serve as biomarkers of endothelium damage in kidney transplant recipients.

Keywords: Anti-endothelial cell antibodies (AECAs); acute rejection; allograft loss; allograft rejection; de novo antibodies; immunofluorescence patterns; kidney transplantation; mortality.