The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients

Ramzannezhad, Somayeh; Tarighi, Mona; Dnia-Afrouzi, Mousa Mohamma; Aghapour, Soudabeh; Bagherzadeh, Mojgan; Ahmadnia, Zahra; Hosseini, Akramasadat; Javanian, Mostafa; Ghorbani, Hossein; Shahbazi, Mehdi

doi:10.1016/j.micpath.2022.105550

Cited by 6 publications

(5 citation statements)

References 29 publications

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“…Several lines of evidence support the role of HLA-G in COVID-19 pathogenesis, including (i) the increased levels of sHLA-G molecules in patients exhibiting various clinical manifestations of the disease [ 14 , 15 , 16 , 17 , 18 ], (ii) the increased number of immune system cells expressing HLA-G [ 16 , 19 ], (iii) the association of the HLA-G 3′untranslated region polymorphism with susceptibility to the disease [ 18 ], (iv) the increased tissue expression of HLA-G in case reports [ 20 , 21 ], and (v) the induction of the expression of hub genes, including HLA-G , in lung tissue infected by SARS-CoV-2 [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule

Cordeiro

Fernandes

Toro

et al. 2022

IJMS

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The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.

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Section: Introductionmentioning

confidence: 99%

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule

Cordeiro

Fernandes

Toro

et al. 2022

IJMS

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“…Critical COVID-19 patients had a significantly lower frequency of CD4 + HLA-G + T lymphocytes compared with moderate/severe COVID-19 patients. The increased amount of immunomodulatory HLA-G + cells may reduce the severity of the disease in moderate/severe COVID-19 patients compared with critical COVID-19 patients (Ramzannezhad et al 2022 ). Furthermore, it is suggested that HLA-G 14-bp Ins/Del polymorphism is associated with COVID-19 risk (Ad’hiah and Al-Bayatee 2019 ).…”

Section: Hla Associations In Sars-cov-2 Infection and Covid-19 Diseas...mentioning

confidence: 99%

The immunogenetics of COVID-19

Hollenbach

Srivastava

2022

Immunogenetics

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The worldwide coronavirus disease 2019 pandemic was sparked by the severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) that first surfaced in December 2019 (COVID-19). The effects of COVID-19 differ substantially not just between patients individually but also between populations with different ancestries. In humans, the human leukocyte antigen (HLA) system coordinates immune regulation. Since HLA molecules are a major component of antigen-presenting pathway, they play an important role in determining susceptibility to infectious disease. It is likely that differential susceptibility to SARS-CoV-2 infection and/or disease course in COVID-19 in different individuals could be influenced by the variations in the HLA genes which are associated with various immune responses to SARS-CoV-2. A growing number of studies have identified a connection between HLA variation and diverse COVID-19 outcomes. Here, we review research investigating the impact of HLA on individual responses to SARS-CoV-2 infection and/or progression, also discussing the significance of MHC-related immunological patterns and its use in vaccine design.

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“…It is possible that patients with the HLA-G Del/Del genotype may express more HLA-G molecules, leading to an increased number of immune-modulatory HLA-G+ cells in the host. In patients with COVID-19 disease, this could reduce the severity by limiting inflammation and cytokine storm responsible for critical cases of illness ( 89 ). Moreover, higher levels of sHLA-G are associated with increased expression of sICAM-1 and sE-selectin expression, which may contribute to improved clinical conditions in COVID-19 patients by reducing neutrophil adhesion to activated endothelium ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G

et al. 2023

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IntroductionA large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection.Materials and MethodsWe compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy).ResultsHLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 – 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3’UTR polymorphism (rs371194629) shows that the HLA-G 3’UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X2 = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X2 = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as β-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3’UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 – 0.7), PM = 6.5 x 10-4].ConclusionOur results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients.

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The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients

Cited by 6 publications

References 29 publications

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule

The immunogenetics of COVID-19

A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G

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