Antibodies against heterogeneous nuclear ribonucleoprotein K in patients with cardiac allograft vasculopathy

Abstract

Cardiac allograft vasculopathy (CAV) is the most serious long-term complication after cardiac transplantation. T-cell-mediated immune response has been implicated as the central mechanism for this form of graft rejection, but the role of humoral immunity is still controversial. This study investigated whether human leukocyte antigen (HLA) and non-HLA antibodies are associated with CAV and if their presence can be used to identify patients at high risk of developing CAV. Diagnosis of CAV was made by angiography and intravascular ultrasound (IVUS) technology. Sera from 48 heart transplant recipients were assessed for the presence of antibodies. Although anti-HLA or anti-major histocompatibility complex class I chain-related gene A (MICA) antibodies in patients with or without CAV were not statistically different, heterogeneous nuclear ribonucleoprotein K (hnRNP-K) was identified as a new antigenic target after the screening of a human coronary artery smooth muscle cells complementary DNA (cDNA) expression library with a serum sample from a CAV patient. Four years after transplantation, presence of anti-hnRNP-K antibodies was significantly higher in the IVUS-defined CAV group (85.3%) and angiography-defined CAV patients (90.5%) compared with the non-CAV group (p < 0.0001 and p = 0.0023 respectively). The presence of anti-hnRNP-K antibodies 4 years after the transplant is statistically associated with CAV disease, regardless of the diagnostic technique. Therefore, prospective detection of these antibodies could be proposed as a helpful biomarker in CAV diagnosis.