Immune biomarkers and long‑term graft survival: a prospective follow‑up of 457 kidney transplant recipients

Abstract

INTRODUCTION Antibodies against donor human leukocyte antigens (HLAs) play a significant role in the pathogenesis of antibody‑mediated rejection, although their relevance during the late posttransplant period is unknown. A non‑HLA polymorphic antigenic system, like major histocompatibility class I chain‑related antigen A (MICA), might be another target for antibody responses involved in rejection. OBJECTIVES We conducted a 7‑year prospective study to determine the effect of positivity for anti‑HLA and anti‑MICA antibodies on kidney graft survival. PATIENTS AND METHODS A random blood sample was collected from 457 kidney recipients during a regular outpatient visit. Patients who were less than 6 months after transplantation were excluded. Evaluation of anti‑HLA (classes I and II) and anti-MICA antibodies was performed with the use of Luminex assays. An outpatient registry was used to monitor kidney function during a 7‑year follow‑up. RESULTS A total of 147 patients (32%) had anti‑HLA and 88 patients (19%) had anti‑MICA antibodies. Graft failure occurred in 67 anti‑HLA‑positive individuals (46%) as compared to 81 anti‑HLA‑negative ones (26%) (P <0.05), and in 30 anti‑MICA‑positive individuals (34%) as compared to 118 anti‑MICA‑negative ones (32%) (P = 0.52). Anti‑HLA antibodies were associated with increased incidence of graft failure: it was reported in 200 patients with an estimated glomerular filtration rate of more than 30 ml/min/1.73 m2 body surface area more than 5 years after transplantation (P <0.005). CONCLUSIONS Anti‑HLA, but not anti‑MICA, antibodies in randomly obtained blood samples were the significant predictor of late kidney graft failure and could be a low‑cost method enabling identification of patients requiring an individualized posttransplant approach. The results of our study provide an additional rationale for investigating immune biomarkers in certain diseases.