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获得性再生障碍性贫血和骨髓增生异常综合征患者血浆中 S100A8 和 S100A9 蛋白水平。

Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes.

机构信息

Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.

Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.

出版信息

Cytokine. 2019 Jan;113:462-465. doi: 10.1016/j.cyto.2018.06.025. Epub 2018 Jun 27.

Abstract

The alarmin family members S100A8 and S100A9 are acute phase inflammation proteins, but they also have been proposed as biomarkers in many malignant and non-malignant diseases. In this study, circulating S100A8 and S100A9 homodimers and S100A8/A9 heterodimers in plasma were systematically investigated by ELISA in aplastic anemia (AA) and myelodysplastic syndromes (MDS). Plasma was obtained from 58 severe AA (SAA) and 30 MDS patients, and from 47 age- and sex-matched healthy donors. In 40 out of the 58 AA subjects, S100A protein levels were measured before and 6 months after immunosuppressive therapy (IST). No differences were observed in AA patients at diagnosis compared to healthy controls for circulating S100A homodimers and heterodimers. After therapy, SAA-responders showed significantly increased circulating S100A8. Non-responding patients had significantly higher levels of circulating S100A8/A9 compared to responders and healthy controls, but without variations of S100A8 and S100A9 homodimers. In MDS patients, circulating S100A8 was significantly elevated compared to those of AA and/or healthy controls. By Pearson correlation analysis of protein levels and blood counts, multiple correlations were found. However, as S100A8 and S100A9 are abundantly present in white blood cells and platelets, correlations with blood counts likely mirror the higher number of cells in the blood of some patients. In conclusion, our findings indicate that circulating S100A8 is increased in MDS but not in AA, and that may be useful to distinguish these diseases in the differential diagnosis of bone marrow failure syndromes. Clinicaltrials.gov identifiers: NCT00260689, NCT00604201, NCT01328587, NCT01623167, NCT00001620, NCT00001397.

摘要

警报素家族成员 S100A8 和 S100A9 是急性炎症蛋白,但它们也被提议作为许多恶性和非恶性疾病的生物标志物。在这项研究中,通过 ELISA 系统地研究了再生障碍性贫血 (AA) 和骨髓增生异常综合征 (MDS) 患者血浆中的循环 S100A8 和 S100A9 同二聚体和 S100A8/A9 异二聚体。从 58 例严重 AA (SAA) 和 30 例 MDS 患者以及 47 名年龄和性别匹配的健康供体中获得了血浆。在 58 例 AA 受试者中有 40 例,在免疫抑制治疗 (IST) 前和 6 个月后测量了 S100 蛋白水平。与健康对照组相比,在诊断时的 AA 患者中,循环 S100A 同二聚体和异二聚体没有差异。在治疗后,SAA 应答者的循环 S100A8 显著增加。无应答患者的循环 S100A8/A9 水平明显高于应答者和健康对照组,但 S100A8 和 S100A9 同二聚体没有变化。与 AA 和/或健康对照组相比,MDS 患者的循环 S100A8 显著升高。通过对蛋白水平和血细胞计数的 Pearson 相关性分析,发现了多种相关性。然而,由于 S100A8 和 S100A9 在白细胞和血小板中大量存在,与血细胞计数的相关性可能反映了一些患者血液中细胞数量的增加。总之,我们的研究结果表明,循环 S100A8 在 MDS 中增加,但在 AA 中不增加,这可能有助于区分骨髓衰竭综合征的这些疾病。临床试验标识符:NCT00260689、NCT00604201、NCT00824346、NCT01328587、NCT00001620、NCT00001397。

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