Division of Hematology, Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
Department of Biomedical Research, National Jewish Health, Denver, Colorado, USA.
J Leukoc Biol. 2018 Sep;104(3):641-647. doi: 10.1002/JLB.5AB1017-419RR. Epub 2018 Apr 14.
Myelodysplastic syndrome (MDS) is a malignant hematopoietic stem cell disorder that frequently evolves into acute myeloid leukemia (AML). Patients with MDS are prone to infectious complications, in part due to the presence of severe neutropenia and/or neutrophil dysfunction. However, not all patients with neutropenia become infected, suggesting that other immune cells may compensate in these patients. Monocytes are also integral to immunologic defense; however, much less is known about monocyte function in patients with MDS. In the current study, we monitor the composition of peripheral blood monocytes and several aspects of monocyte function in MDS patients, including HLA-DR expression, LPS-induced inflammatory cytokine production, and phagocytosis. We find that monocytes from MDS patients exhibit relatively normal innate immune functions compared to monocytes from healthy control subjects. We also find that HLA-DR expression is moderately increased in monocytes from MDS patients. These results suggest that monocytes could compensate for other immune deficits in MDS patients to help fight infection. We also find that the range of immune functions in monocytes from MDS patients correlates with several key clinical parameters, including blast cell count, monocyte count, and revised International Prognostic Scoring System score, suggesting that disease severity impacts monocyte function in MDS patients.
骨髓增生异常综合征(MDS)是一种恶性造血干细胞疾病,常发展为急性髓系白血病(AML)。MDS 患者易发生感染并发症,部分原因是严重中性粒细胞减少和/或中性粒细胞功能障碍。然而,并非所有中性粒细胞减少的患者都会感染,这表明其他免疫细胞可能在这些患者中发挥代偿作用。单核细胞也是免疫防御的重要组成部分;然而,人们对 MDS 患者单核细胞功能的了解要少得多。在目前的研究中,我们监测 MDS 患者外周血单核细胞的组成和单核细胞功能的几个方面,包括 HLA-DR 表达、LPS 诱导的炎症细胞因子产生和吞噬作用。我们发现 MDS 患者的单核细胞与健康对照组的单核细胞相比,具有相对正常的固有免疫功能。我们还发现 MDS 患者的单核细胞中 HLA-DR 表达中度增加。这些结果表明,单核细胞可以代偿 MDS 患者的其他免疫缺陷,帮助抵抗感染。我们还发现 MDS 患者单核细胞的免疫功能范围与几个关键的临床参数相关,包括原始细胞计数、单核细胞计数和修订后的国际预后评分系统评分,表明疾病严重程度影响 MDS 患者的单核细胞功能。