The predictive value of soluble major histocompatibility complex class I chain-related molecule A (MICA) levels on heart allograft rejection

Transplantation. 2006 Aug 15;82(3):354-61. doi: 10.1097/01.tp.0000228911.22944.23.

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Biopsy
  • Cell Line
  • Down-Regulation
  • Female
  • Follow-Up Studies
  • Graft Rejection / blood*
  • Graft Rejection / immunology*
  • Heart Transplantation* / immunology
  • Histocompatibility Antigens Class I / blood*
  • Histocompatibility Antigens Class I / classification
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily K
  • Rabbits
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell
  • Solubility
  • Transplantation, Homologous / immunology

Substances

  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell