Abstract 4019: Human Leukocyte Antigen-G (HLA-G) is Upregulated in Heart Failure Patients: A Potential Novel Biomarker
Background: Immune activation and inflammation play critical roles in heart failure (HF). Human leukocyte antigen-G (HLA-G) is a tolerogenic, non-classical MHC-I protein, primarily expressed by fetal trophoblast cells. HLA-G is upregulated in response to transplantation, malignancy and inflammation, and has been correlated to various clinical outcomes in numerous studies. Our investigation assessed the role of HLA-G in HF patients by comparing plasma HLA-G concentrations with other clinical and laboratory markers of HF.
Methods: This single-centre cross-sectional pilot study involved patients followed in HF clinics at our institution. Blood samples were collected into EDTA-containing tubes and centrifuged for 20 min at 4 °C. Plasma was isolated, flash frozen and stored at −80 °C within 4 h of blood collection. Concentrations of circulating HLA-G and inflammatory markers were detected with specific ELISA kits and quantified according to purified protein standards.
Results: Eighty-two patients (mean age 51±11 years, 65% males) were included in the study. The etiology of heart failure was: non-ischemic in 69.9%, and ischemic in 31.1%. The distribution of patients according to NYHA class was: 12.2% class-I, 56.1% class-II, 20.7% class-III, and 11% class-IV. The mean left ventricular ejection fraction (LVEF) was 31.6% ±11, VO2 max was 16.1±4.5ml/kg/min and B-type natriuretic peptide (BNP) was 447.7±573.6 pg/mL. Levels of Interleukins (IL) 1β, IL-6, IL-10 and Tumour Necrosis Factor alpha (TNF-α) were as follow; 0.29 pg/ml, 2.87 pg/ml, 2.99 pg/ml, 0.49 pg/ml respectively. Using ten healthy individuals as control group (plasma HLA-G =29.5 ±8.5 U/mL), HLA-G levels were significantly increased in patients diagnosed with HF (84.1 ±63.2 U/mL; p<0.001)). There was a trend toward higher HLA-G levels in advanced HF patients (NYHA Class-I: 66.2±40, Class-II: 85.9 ±63.6 and Class-III: 97.3±82 U/mL; p=0.57). There was no correlation between plasma HLA-G and other biomarkers including IL-1β, IL-6, IL10, TNF-α, and BNP.
Conclusion: This is the first study to show increased HLA-G in HF patients. While the role of HLA-G as a predictor of outcomes in HF needs to be further investigated, HLA-G might prove more reliable than classical biological markers of HF.