Patrón de expresión de los niveles séricos de HLA-G y su relación con la evolución clínica de los pacientes tras el trasplante cardiaco

Abstract

Introduction: HLA-G has been described to be produced by allografts and infiltrating mononuclear cells within the transplanted tissues. The expression of HLA-G is induced in pathological situations such autoimmune disorders, inflammation, viral infections, cancer and transplantation. High levels of soluble HLA-G (sHLA-G) have been significantly related with better graft acceptance in hematopoietic stem cell-, heart-, kidney- and liver/kidney transplants Purpose: To describe the evolution of s-HLA-G during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes. Methods: Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. sHLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of sHLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of sHLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of cardiac allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year. Long-term outcomes evaluated in this study were overall survival, survival free of late graft failure and survival free of cancer. Mean follow-up was 12.4 years. Results: Levels of sHLA-G decreased over the first post-transplant year (p=0.020). The AUC of sHLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of sHLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of sHLA-G levels higher or lower than the median of the study population. Conclusions: Levels of sHLA-G decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.