Dataset Information

Increased Circulating of CD54^highCD181^low Neutrophils in Myelodysplastic Syndrome.

ABSTRACT: Myelodysplastic syndromes (MDSs) are a group of heterogeneous hematopoietic stem/progenitor cells clonal diseases, characteristic features with myeloid dysplasia, leading to abnormality of neutrophils. Recent studied have showed that neutrophils act not only as professional killers, but also as regulators of innate and adaptive immune in infection and inflammatory condition. The CD54^highCD181^low neutrophils are a kind of reverse-transmigrated neutrophils characterized proinflammatory phenotype. We investigated the frequency and functional properties of circulating CD54^highCD181^low neutrophils in patients with untreated MDS. Frequency of CD54^highCD181^low neutrophils was significantly increased in MDS patients and related to the severity of the disease. Furthermore, CD54^highCD181^low neutrophils suppressed CD8+ T cells functions in vitro. CD54^highCD181^low neutrophils lead to upregulation of PD1 on CD8+ T cells. Higher CD54^highCD181^low neutrophils were related to poor prognosis and more infections. The frequency of CD54^highCD181^low neutrophils decreased in high risk MDS patients who had response after treatment with decitabine. Overall, we identified CD54^highCD181^low neutrophils expanded in MDS. The exact mechanisms of increased CD54^highCD181^low neutrophils and its effect on immune function remain to be elucidated.

SUBMITTER: Yang L

PROVIDER: S-EPMC7830137 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Increased Circulating of CD54highCD181low Neutrophils in Myelodysplastic Syndrome.

Yang Liyan L Li Hongzhao H Liu Yumei Y Xie Xinyan X Zhang Huiqin H Niu Haiyue H Shao Zonghong Z Xing Limin L Wang Huaquan H

Frontiers in oncology 20210111

Myelodysplastic syndromes (MDSs) are a group of heterogeneous hematopoietic stem/progenitor cells clonal diseases, characteristic features with myeloid dysplasia, leading to abnormality of neutrophils. Recent studied have showed that neutrophils act not only as professional killers, but also as regulators of innate and adaptive immune in infection and inflammatory condition. The CD54highCD181low neutrophils are a kind of reverse-transmigrated neutrophils characterized proin ...[more]

PMID: 33505909

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Project description:BackgroundMyelodysplastic syndrome (MDS) is associated with persistent immune activation. High mobility group box-1 (HMGB1) is a ubiquitous, functionally diverse, non-histone intranuclear protein. During acute and chronic inflammatory states, HMGB1 is actively released by inflammatory cells, further amplifying the inflammatory response. A role in MDS and other hypoplastic bone marrow (BM) disorders is incompletely understood.ObjectivesThe objective of the study is to evaluate whether circulating HMGB1 is elevated in patients with MDS and other BM failure syndromes [namely, aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH)].DesignThis is a observational, cross-sectional, single-center, exploratory study.MethodsWe evaluated circulating concentrations of HMGB1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in patients with MDS and age-matched hematologically healthy controls as well as patients with AA and PNH.ResultsWe included 66 patients with MDS and 65 age-matched controls as well as 44 patients with other BM failures (AA = 27, PNH = 17). Circulating levels of HMGB1 were higher in patients with MDS [median, 4.9 ng/ml; interquartile range (IQR): 2.3-8.1] than in AA (median, 2.6 ng/ml; IQR: 1.7-3.7), PNH (median, 1.7 ng/ml; IQR: 0.9-2.5), and age-matched healthy individuals (median, 1.9 ng/ml; IQR: 0.9-2.5) (p = 0.0001). We observed higher concentrations of HMGB1 in the very low/low-risk MDS patients than in the intermediate/high/very high-risk ones (p = 0.046). Finally, in comparison with patients with AA, those with hypocellular MDS (h-MDS) had significantly higher levels of circulating HMGB1 (n = 14; median concentration, 5.6 ng/ml, IQR: 2.8-7.3; p = 0.006). We determined a circulating HMGB1 value of 4.095 ng/ml as a diagnostic cutoff differentiator between h-MDS and AA.ConclusionThese observations indicate that circulating HMGB1 is increased in patients with MDS. HMGB1 (but not IL-1β or TNF-α) differentiated between MDS and other BM failures, suggesting that HMGB1 may be mechanistically involved in MDS and a druggable target to decrease inflammation in MDS.

Dataset Information

Increased Circulating of CD54^highCD181^low Neutrophils in Myelodysplastic Syndrome.

Publications

Increased Circulating of CD54<sup>high</sup>CD181<sup>low</sup> Neutrophils in Myelodysplastic Syndrome.

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