26. |
- von Bahr Greenwood, Tatiana, et al.
(författare)
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Elevated ferritin and soluble CD25 in critically ill are associated with parameters of (hyper)inflammation and lymphocyte cytotoxicity
- 2019
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Ingår i: Minerva Anestesiologica. - : Edizioni Minerva Medica. - 0375-9393 .- 1827-1596. ; 85:12, s. 1289-1298
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Critically ill may develop a potentially fatal hyperinflammation, secondary (acquired) hemophagocytic lymphohistiocytosis (sHLH), the cause of which is unclear. We evaluated serum ferritin and soluble CD25 (sCD25) in critically ill, and their association with other parameters of inflammation and critical illness. Moreover, aiming to better understand the pathogenesis of sHLH, we also evaluated lymphocyte cytotoxicity parameters and correlations with the inflammatory markers ferritin and sCD25.METHODS: In a prospective observational study, 32 patients with ferritin ≥500 μg/L (24 with sepsis) were studied on admission to an intensive care unit (ICU) with regard to ferritin and corresponding clinical and laboratory features including sCD25, and detailed lymphocyte cytotoxicity and genetic analyses whenever possible.RESULTS: Critically ill patients had elevated, positively correlated levels of serum ferritin and sCD25 (rs=0.465, p=0.008); both associated with other risk factors of poorer outcome in critically ill, such as thrombocytopenia (rs=-0.534, p=0.002 and rs=-0.421, p=0.018, respectively), and sCD25 with hypoalbuminemia (rs=-0.678, p<0.001) and life support treatments (rs=0.479, p=0.006). Interestingly, ferritin levels were inversely associated with NK- cell cytotoxicity (rs=-0.462, p=0.047) and degranulation (rs=-0.504, p=0.030). Moreover, of four patients with abnormally low cytotoxicity, three (75%) had <5% circulating NK-cells.CONCLUSIONS: Our study suggests that hyperferritinemia and sCD25 correlate with other laboratory parameters indicative of severe hyperinflammation and organ dysfunction in critically ill ICU-patients, indicating their value in identifying hyperinflammatory critically ill patients for early intervention. Furthermore, it suggests that hyperferritinemia and hyperinflammation may partly be associated with a low percentage circulating NK-cells, and hence, the associated low lymphocyte cytotoxicity.
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27. |
- Zitti, Beatrice, et al.
(författare)
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Human skin-resident CD8+T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a
- 2023
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Ingår i: Immunity. - : CELL PRESS. - 1074-7613 .- 1097-4180. ; 56:6, s. 1285-1302.e7
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Tidskriftsartikel (refereegranskat)abstract
- The integrin CD49a marks highly cytotoxic epidermal-tissue-resident memory (TRM) cells, but their differen-tiation from circulating populations remains poorly defined. We demonstrate enrichment of RUNT family tran-scription-factor-binding motifs in human epidermal CD8+CD103+CD49a+ TRM cells, paralleled by high RUNX2 and RUNX3 protein expression. Sequencing of paired skin and blood samples revealed clonal overlap be-tween epidermal CD8+CD103+CD49a+ TRM cells and circulating memory CD8+CD45RA-CD62L+ T cells. In vitro stimulation of circulating CD8+CD45RA-CD62L+ T cells with IL-15 and TGF-b induced CD49a expres-sion and cytotoxic transcriptional profiles in a RUNX2-and RUNX3-dependent manner. We therefore identi-fied a reservoir of circulating cells with cytotoxic TRM potential. In melanoma patients, high RUNX2, but not RUNX3, transcription correlated with a cytotoxic CD8+CD103+CD49a+ TRM cell signature and improved pa-tient survival. Together, our results indicate that combined RUNX2 and RUNX3 activity promotes the differ-entiation of cytotoxic CD8+CD103+CD49a+ TRM cells, providing immunosurveillance of infected and malig-nant cells.
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