Peripheral HLA-G/ILT-2 immune checkpoint axis in acute and convalescent COVID-19 patients.
Hana RohnSabine SchrammKrystallenia PansikakiSarah JansenCelina HendriksMaximilian PlatteMargarethe J KonikSebastian DolffBenjamin WildeLambros KordelasMirko TrillingAdalbert KrawczykPeter A HornOliver WitzkeVera RebmannPublished in: Human immunology (2023)
The immunosuppressive non-classical human leukocyte antigen-G (HLA-G) can elicits pro-viral activities by down-modulating immune responses. We analysed soluble forms of HLA-G, IL-6 and IL-10 as well as on immune effector cell expression of HLA-G and its cognate ILT-2 receptor in peripheral blood obtained from hospitalised and convalescent COVID-19 patients. Compared with convalescents (N = 202), circulating soluble HLA-G levels (total and vesicular-bound molecules) were significantly increased in hospitalised patients (N = 93) irrespective of the disease severity. During COVID-19, IL-6 and IL-10 levels were also elevated. Regarding the immune checkpoint expression of HLA-G/ILT-2 on peripheral immune effector cells, the frequencies of membrane-bound HLA-G on CD3+ and CD14+ cells were almost identical in patients during and post COVID-19, while the frequency of ILT-2 receptor on CD3+ and CD14+ cells was increased during acute infection. A multi-parametric correlation analysis of soluble HLA-G forms with IL-6, IL-10, activation markers CD25 and CD154, HLA-G, and ILT-2 expression on immune cells revealed a strong positive correlation of soluble HLA-G forms with membrane-bound HLA-G molecules on CD3+/CD14+ cells only in convalescents. During COVID-19, only vesicular-bound HLA-G were positively correlated with the activation marker CD25 on T cells. Thus, our data suggest that the elevated levels of soluble HLA-G in COVID-19 are due to increased expression in organ tissues other than circulating immune effector cells. The concomitant increased expression of soluble HLA-G and ILT-2 receptor frequencies supports the concept that the immune checkpoint HLA-G/ILT-2 plays a role in the immune-pathogenesis of COVID-19.
Keyphrases
- induced apoptosis
- sars cov
- poor prognosis
- coronavirus disease
- cell cycle arrest
- end stage renal disease
- immune response
- peripheral blood
- dendritic cells
- chronic kidney disease
- newly diagnosed
- ejection fraction
- endoplasmic reticulum stress
- liver failure
- regulatory t cells
- endothelial cells
- long non coding rna
- intensive care unit
- stem cells
- prognostic factors
- cell therapy
- acute respiratory distress syndrome
- respiratory failure
- electronic health record
- heat stress
- patient reported