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

Area of Science:

• Cardiology
• Immunology
• Biomarker Discovery

Background:

• Left ventricular systolic dysfunction (LVSD), defined by ejection fraction (EF) <40%, is a prevalent and serious cardiac condition requiring accurate diagnosis for effective treatment.
• The immune system's activation in LVSD suggests a role for immunomodulatory molecules like human leukocyte antigen-G (HLA-G).
• Soluble HLA-G (sHLA-G) is an immunomodulatory molecule that may be involved in the pathophysiology of LVSD.

Purpose of the Study:

• To measure soluble HLA-G (sHLA-G) levels in different stages of LVSD and preserved ejection fraction (EF) in elderly individuals.
• To validate sHLA-G as a potential biomarker for diagnosing LVSD.
• To investigate the association between HLA-G gene polymorphisms and LVSD.

Main Methods:

• Blood samples were collected from 260 elderly participants (≥75 years) with varying degrees of LVSD and preserved EF.
• Soluble HLA-G (sHLA-G) levels were measured using plasma assays.
• N-terminal fragment-pro-B-type natriuretic peptide (NT-proBNP) and uric acid levels were also assessed, alongside HLA-G gene polymorphism analysis.

Main Results:

• Soluble HLA-G (sHLA-G) levels were significantly higher in participants with EF < 50% compared to those with EF ≥ 50% (p < 0.0001).
• NT-proBNP and uric acid levels showed an inverse relationship with EF.
• Receiver Operating Characteristic (ROC) curve analysis indicated that NT-proBNP outperformed both sHLA-G and uric acid as a biomarker for LVSD.

Conclusions:

• Soluble HLA-G is elevated in patients with LVSD, irrespective of ejection fraction, suggesting its involvement in the condition.
• A specific HLA-G haplotype (14 bp ins-del/+3142 SNP) was found to be associated with EF < 40%.
• While sHLA-G shows potential, NT-proBNP remains a more robust biomarker for diagnosing LVSD in this elderly cohort.