The Predictive Value of Soluble Major Histocompatibility Complex Class I Chain-Related Molecule A (MICA) Levels on Heart Allograft Rejection

Abstract

Recently the presence of a soluble form of major histocompatibility complex class I chain-related molecule A (sMICA) has been detected in the sera of patients with tumors. Shedding of sMICA by tumor cells downregulates NKG2D-mediated antitumor immunity. The aim of this investigation was to study the possible involvement of sMICA in the allograft acceptance after heart transplantation (HTX). We monitored the levels of sMICA by specific enzyme-linked immunosorbent assay (ELISA) in a total of 146 serum samples obtained from 34 heart transplantation patients followed up during the first year post-HTX. The persistence of sMICA expression was correlated with the clinical evolution of these patients. sMICA was detected in the serum of 21 of 34 patients (61.70%) between 15 and 20 days after implantation and was practically absent in pretransplant serum samples. Twenty of these 21 patients (95.24%) with sMICA did not experience episodes of severe rejection during this period (P = 0.0001), whereas sMICA was practically absent in patients with manifestations of severe acute rejection. The longitudinal study of these patients revealed that the presence of sMICA was consistently maintained in 75% of the patients with good graft status during the period of observation. This has led us to believe that the presence of levels of sMICA during the first year post-HTX may contribute to allograft acceptance. Additionally, functional studies indicate that sMICA downregulates NKG2D surface expression, which may lead to a functional impairment of cell-mediated cytolysis. These data suggest a significant correlation between the presence of sMICA and a lower incidence of rejection.