Human leukocyte antigen–G is upregulated in heart failure patients: A potential novel biomarker

Almasood, Ali; Sheshgiri, Rohit; Joseph, Jemy; Rao, Vivek; Ghahramani, Sulmaz; Tumiati, Laura C.; Ross, Heather J.; Delgado, Diego

doi:10.1016/j.humimm.2011.08.016

Cited by 16 publications

(10 citation statements)

References 29 publications

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“…There was no difference in the concentration of sHLA-G in LVSD patients with EF < 30% and with EF between 30 and 40%. Thus, sHLA-G in the blood plasma does not indicate the severity of LVSD, and, in accordance with the study by Almasood et al, we conclude that sHLA-G is a very sensitive LVSD biomarker [ 8 , 9 , 24 ]. The assay used in the current study detects both soluble HLA-G5 and soluble HLA-G1 associated with β 2-microglobulin.…”

Section: Discussionsupporting

confidence: 90%

“…A single published study has indicated that soluble HLA-G (sHLA-G) in plasma is upregulated in patients with systolic heart failure, compared to healthy controls, and independent of NYHA class, EF, and other biomarkers [ 24 ]. The study included only ten control subjects who were markedly younger than the participants in the present study.…”

Section: Introductionmentioning

confidence: 99%

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

Olesen

Hviid

2016

Journal of Immunology Research

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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%.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

Olesen

Hviid

2016

Journal of Immunology Research

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“…To provide novel and further data on the impact of the most frequent variation sites described at the HLA-G 3’UTR on the plasma soluble HLA-G (sHLA-G) levels we typed the complete HLA-G 3’UTR, defining alleles, genotypes, haplotypes and diplotypes in two distinct Brazilian and French populations. Considering that the differential expression of sHLA-G has been primarily associated with the outcome of allotransplanted organs [33], the identification of individuals genetically committed to produce higher or lower HLA-G levels is quite justifiable and clinically relevant.…”

Section: Introductionmentioning

confidence: 99%

Polymorphic Sites at the 3’ Untranslated Region of the HLA-G Gene Are Associated with Differential hla-g Soluble Levels in the Brazilian and French Population

et al. 2013

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HLA-G molecule has well-recognized tolerogenic properties, and the encoding gene shows lower frequency of polymorphism at the coding region but higher variability at regulatory 5’ and 3’ untranslated (3’UTR) regions. At least three 3’UTR polymorphic sites have been associated with HLA-G mRNA regulation, including the 14 base pair (14bp) Insertion/Deletion, +3142C-G and +3187A-G. We studied the association of polymorphic sites at 3’UTR (sequencing analysis, encompassing the 14bp Ins-Del/+3003T-C/+3010C-G/+3027C-A/+3035C-T/+3142C-G/+3187A-G/+3196C-G polymorphic sites) with plasma soluble HLA-G levels (sHLA-G, detected by ELISA) in 187 French and 153 Brazilian healthy individuals. Allele and genotype frequencies were closely similar in both populations; however, Brazilians showed a higher HLA-G 3’UTR haplotype diversity. Considering sHLA-G levels in both populations altogether, individuals presenting 14bp Del/Del showed higher levels compared to 14bpIns/Ins genotype (P <0.05); those presenting +3010C/G showed higher levels compared to the +3010C-C genotype (P< 0.05); those presenting +3027C-C showed higher levels than the +3027A-A genotype (P< 0.05); and those bearing +3035C-C showed higher levels compared to the +3035C-T (P < 0.01) and +3035T-T (P < 0.05) genotypes. The analyses of 3’UTR haplotypes showed that UTR-1 (DelTGCCCGC) was associated with higher expression of sHLA-G, whereas UTR-5 (InsTCCTGAC) and UTR-7 (InsTCATGAC) with lower expression and other UTRs (UTR-2/3/4/6) exhibited intermediate levels. Since the differential expression of HLA-G may be beneficial or harmful depending on the underlying condition, the identification of individuals genetically programmed to differentially express HLA-G may help on defining novel strategies to control the immune response against the underlying disorder.

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“…Serum levels increased post-transplantation in patients with good graft function but were significantly decreased in those suffering from cardiac allograft vasculopathy [9]. However, levels of soluble HLA-G were also found to be increased in patients suffering from heart failure [10]. In lung transplant patients, bronchial epithelial expression of HLA-G was more prominent in patients with good graft function than in those with signs of acute rejection and anti-HLA antibodies [11,12].…”

Section: Introductionmentioning

confidence: 98%

Changes in HLA-G Expression by Leucocyte Subsets Following Renal Transplantation and the Effect of Immunosuppressive Drugs on Leucocyte HLA-G Expression in Vitro

Al-Bayati¹,

Heyworth²,

Moberly³

et al. 2018

obm transplant

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Background: HLA-G is an immunosuppressive molecule with a potential role in allograft acceptance. Methods: Expression of HLA-G on leucocyte subpopulations was studied in a group of 21 renal transplant patients immediately prior to and 2 months post-transplantation. Results: Significant increases in proportions of total HLA-G+CD4+ T cells were seen (0.5+/-0.1% to 7.9+/-3.2%; p<0.01) and also for CD45RA+, CD45RO+ and CD69+ subsets. Increases in proportions of HLA-G+ cells were also seen in CD8+ T cells and their subsets, CD56+ T cells, B cells, NK cells and monocytes, and also of serum soluble HLA-G, but these did not reach statistical significance. When leucocytes from healthy subjects were cultured for 7 days in

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Human leukocyte antigen–G is upregulated in heart failure patients: A potential novel biomarker

Cited by 16 publications

References 29 publications

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

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

Polymorphic Sites at the 3’ Untranslated Region of the HLA-G Gene Are Associated with Differential hla-g Soluble Levels in the Brazilian and French Population

Changes in HLA-G Expression by Leucocyte Subsets Following Renal Transplantation and the Effect of Immunosuppressive Drugs on Leucocyte HLA-G Expression in Vitro

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