Isolated De Novo Antiendothelial Cell Antibodies and Kidney Transplant Rejection

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 + /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.