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低维生素D的小儿输血依赖型地中海贫血中炎症性单核细胞亚群与铁水平的相关性

Inflammatory Monocyte Subsets Correlation with Iron Levels in Low Vitamin D Pediatric Transfusion-Dependent Thalassemia.

作者信息

Ghozali Mohammad, Matahari Matahari, Cahyadi Adi Imam, Agustini Sri Devi, Ghrahani Reni, Reniarti Lelani, Setiabudiawan Budi, Panigoro Ramdan

机构信息

Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, 45363, Indonesia.

Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, 45363, Indonesia.

出版信息

J Inflamm Res. 2025 Jan 8;18:421-429. doi: 10.2147/JIR.S476688. eCollection 2025.

DOI:10.2147/JIR.S476688
PMID:39802505
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11725247/
Abstract

BACKGROUND

Patients with transfusion-dependent thalassemia experience iron dysregulation, which affects the immune response. Surface proteins such as FcγRIII (CD16), lipopolysaccharide receptor (CD14), and human leukocyte antigen (HLA-DR) on monocytes are crucial for innate and adaptive responses. Blood monocytes, identified by their CD14 and CD16 expression, show functional diversity during injury or inflammation. Considering the mechanisms of vitamin D activation and its potential interaction with monocytes, further investigation of its immunomodulatory role in transfusion-dependent thalassemia is essential.

PURPOSE

This study evaluated monocyte subsets, population, and surface receptor expression (CD14, CD16, and HLA-DR), and their association with iron status and vitamin D levels in patients with transfusion-dependent thalassemia.

PATIENTS AND METHODS

Fifty lysed erythrocyte-heparinized whole blood samples from transfusion-dependent thalassemia patients were analyzed by flow cytometry and classified into three monocyte subsets: CD14++CD16- (classical), CD14++CD16+ (intermediate), and CD14+CD16++ (non-classical). Cell percentage referred to the monocyte subset population. Median fluorescence intensity (MFI) indicated surface protein expression. The 25(OH)vitamin D level was used to measure vitamin D levels. Iron status was assessed using ferritin and serum iron levels. A correlational study was performed.

RESULTS

We did not find a correlation between low vitamin D levels (22.9 ng/mL ± 3.9) and monocyte characteristics, iron status, or hematology profile. However, we observed a negative correlation between the percentage of intermediate and non-classical monocytes and hemoglobin and ferritin levels (P = 0.02, r = -0.3; P = 0.04, r = -0.3). Additionally, we found a positive correlation between the median fluorescence intensity (MFI) of CD14 in non-classical monocytes and serum iron (P = 0.04, r = 0.3).

CONCLUSION

Our findings suggest that iron overload and anemia may influence the function of inflammatory monocyte subsets. Considering the immunomodulatory role of vitamin D through monocyte modulation during pathogen insult, further research utilizing a whole-blood stimulation assay is imperative.

摘要

背景

依赖输血的地中海贫血患者存在铁调节异常,这会影响免疫反应。单核细胞表面的蛋白质,如FcγRIII(CD16)、脂多糖受体(CD14)和人类白细胞抗原(HLA - DR),对先天性和适应性免疫反应至关重要。根据CD14和CD16表达鉴定的血液单核细胞在损伤或炎症期间表现出功能多样性。考虑到维生素D激活的机制及其与单核细胞的潜在相互作用,进一步研究其在依赖输血的地中海贫血中的免疫调节作用至关重要。

目的

本研究评估了依赖输血的地中海贫血患者的单核细胞亚群、数量及其表面受体表达(CD14、CD16和HLA - DR),以及它们与铁状态和维生素D水平的关系。

患者和方法

采用流式细胞术分析了50份来自依赖输血的地中海贫血患者的溶血红细胞 - 肝素化全血样本,并将单核细胞分为三个亚群:CD14++CD16-(经典型)、CD14++CD16+(中间型)和CD14+CD16++(非经典型)。细胞百分比代表单核细胞亚群数量。中位荧光强度(MFI)表示表面蛋白表达。采用25(OH)维生素D水平来测量维生素D水平。使用铁蛋白和血清铁水平评估铁状态。进行了相关性研究。

结果

我们未发现低维生素D水平(22.9 ng/mL ± 3.9)与单核细胞特征、铁状态或血液学指标之间存在相关性。然而,我们观察到中间型和非经典型单核细胞的百分比与血红蛋白和铁蛋白水平之间存在负相关(P = 0.02,r = -0.3;P = 0.04,r = -0.3)。此外,我们发现非经典型单核细胞中CD14的中位荧光强度(MFI)与血清铁之间存在正相关(P = 0.04,r = 0.3)。

结论

我们的研究结果表明,铁过载和贫血可能影响炎性单核细胞亚群的功能。考虑到在病原体侵袭期间维生素D通过调节单核细胞发挥的免疫调节作用,利用全血刺激试验进行进一步研究势在必行。

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本文引用的文献

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Monocyte Differentiation and Heterogeneity: Inter-Subset and Interindividual Differences.单核细胞分化和异质性:亚群间和个体间差异。
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Utility of monocyte HLA-DR and rationale for therapeutic GM-CSF in sepsis immunoparalysis.脓毒症免疫麻痹中单核细胞 HLA-DR 的作用及治疗性 GM-CSF 的作用机制。
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