Upregulation of Soluble HLA-G in Chronic Left Ventricular Systolic Dysfunction.

Line Lisbeth Olesen,Thomas Vauvert F Hviid

doi:10.1155/2016/8417190

Abstract

Left ventricular systolic dysfunction (LVSD) defined by ejection fraction (EF) <40% is common, serious but treatable, and correct diagnosis is the cornerstone of effective treatment. Biomarkers may help to diagnose LVSD and give insight into the pathophysiology. The immune system is activated in LVSD, and the immunomodulatory molecule human leukocyte antigen-G (HLA-G) may be involved. The primary aim was to measure soluble HLA-G (sHLA-G) in the blood in different stages of LVSD (<30% and 30–40%), in the midrange EF 40–50%, and in preserved EF ≥ 50% and to validate sHLA-G as a LVSD biomarker. The secondary aim was to examine associations between HLA-G gene polymorphisms influencing expression levels and LVSD. The 260 study participants were ≥75 years old, many with risk factors for heart disease or with known heart disease. Soluble HLA-G was significantly and uniformly higher in the groups with EF < 50% (<30, 30–40, and 40–50%) compared to EF > 50% (p < 0.0001). N-terminal fragment-pro-B-type natriuretic peptide (NT-proBNP) and uric acid values were inversely related to EF. According to Receiver Operating Characteristic (ROC) curves NT-proBNP outperformed both sHLA-G and uric acid as biomarkers of LVSD. Soluble HLA-G in blood plasma was elevated in LVSD regardless of EF. A novel finding was that a combined 14 bp ins-del/+3142 SNP HLA-G haplotype was associated with EF < 40%.

Highlights

The new European guidelines for heart failure define three groups based on ejection fraction (EF): a group with reducedEF < 40% (left ventricular systolic dysfunction (LVSD)); a group in the grey zone with EF in the midrange 40–49%; and a group with preserved EF ≥ 50%
SHLAG in the blood plasma does not indicate the severity of Left ventricular systolic dysfunction (LVSD), and, in accordance with the study by Almasood et al, we conclude that soluble Human leukocyte antigen (HLA)-G (sHLA-G) is a very sensitive LVSD biomarker
The assay used in the current study detects both soluble HLA-G5 and soluble HLA-G1 associated with β2microglobulin

Summary

Introduction

EF < 40% (left ventricular systolic dysfunction (LVSD)); a group in the grey zone with EF in the midrange 40–49%; and a group with preserved EF ≥ 50%. Left ventricular systolic dysfunction affects about 2% of the population in the western world, including many with unrecognized LVSD. It accumulates in the elderly population because LVSD is the final stage in most cardiac diseases, mostly caused by atherosclerosis in the coronary arteries [3]. Screening for systolic heart failure in high risk populations should be considered because correct diagnosis is the cornerstone of effective treatment

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