Post-transplant increase in soluble human leukocyte antigen-G associated with non-severe cardiac allograft vasculopathy

Hum Immunol. 2013 Mar;74(3):318-24. doi: 10.1016/j.humimm.2012.12.001. Epub 2012 Dec 14.

Abstract

Cardiac allograft vasculopathy (CAV) is the single most important long-term limitation to heart transplantation. This study aimed to assess the value of monitoring soluble human leukocyte antigen-G (sHLA-G) during the first year post-transplantation to predict the severity of CAV, in 21 out of 77 heart recipients assessed by intravascular ultrasound (IVUS). Serum sHLA-G concentration increased after transplant in recipients free of severe CAV, but decreased in recipients suffering from severe CAV, significant differences between these two groups were found 6 to 12 months post-transplantation. The optimal value of the change in post-transplant sHLA-G for identifying severe CAV was ≥0.062%, which maximized sensitivity (80%) and specificity (100%). Importantly, increases in post-transplant sHLA-G were inversely associated with severe CAV, but directly associated with human cytomegalovirus reactivation. In addition, recipients presenting non-severe CAV or an increased sHLA-G post-transplantation, showed higher numbers of CD8(+)CD28(-) T cells and a down-modulation of CD28 on CD4(+) lymphocytes, which typically identifies CD8(+) regulatory T cells and anergic/tolerogenic T helper cells, respectively. In conclusion, quantification of sHLA-G might offer a complementary non-invasive method for identifying recipients at risk of more severe CAV and who might benefit from earlier preventive therapies, although these results need to be confirmed in larger series.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / virology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HLA-G Antigens / blood
  • HLA-G Antigens / immunology*
  • HLA-G Antigens / metabolism
  • Heart Transplantation / adverse effects
  • Heart Transplantation / immunology*
  • Heart Transplantation / methods
  • Humans
  • Hyperplasia / blood
  • Hyperplasia / etiology
  • Hyperplasia / immunology
  • Male
  • Middle Aged
  • Postoperative Period
  • Severity of Illness Index
  • Solubility
  • Time Factors
  • Transplantation, Homologous
  • Tunica Intima / diagnostic imaging
  • Tunica Intima / immunology*
  • Tunica Intima / pathology
  • Ultrasonography, Interventional
  • Virus Activation / immunology

Substances

  • CD28 Antigens
  • HLA-G Antigens