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铍中毒性疾病患者中表达铍特异性、TH1型细胞因子的CD4 + T细胞的频率。

Frequency of beryllium-specific, TH1-type cytokine-expressing CD4+ T cells in patients with beryllium-induced disease.

作者信息

Pott Gregory B, Palmer Brent E, Sullivan Andrew K, Silviera Lori, Maier Lisa A, Newman Lee S, Kotzin Brian L, Fontenot Andrew P

机构信息

Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.

出版信息

J Allergy Clin Immunol. 2005 May;115(5):1036-42. doi: 10.1016/j.jaci.2005.01.019.

DOI:10.1016/j.jaci.2005.01.019
PMID:15867863
Abstract

BACKGROUND

Beryllium sensitization is caused by exposure to beryllium in the workplace. A subset of beryllium-sensitized (BeS) subjects progress to chronic beryllium disease (CBD), a disorder characterized by a CD4+ T-cell alveolitis and granulomatous inflammation. Whether biomarkers are present in blood that would allow separation of CBD from beryllium sensitization without invasive pulmonary procedures is unknown.

OBJECTIVE

The aim of this study was to determine whether the quantity of beryllium-specific T cells in blood of patients with CBD differs from that found in BeS subjects.

METHODS

Beryllium-induced T-cell proliferation and T H 1-type cytokine secretion were determined in blood cells from 33 patients with CBD and 18 BeS subjects.

RESULTS

We demonstrate here that patients with CBD have a significantly elevated number of IFN-gamma-producing and IL-2-producing beryllium-specific CD4+ T cells in blood compared with both BeS and normal control subjects. In contrast, no difference in beryllium-induced proliferation of blood T cells was seen between BeS patients and patients with CBD. Compared with the blood beryllium lymphocyte proliferation test, which detected beryllium-induced proliferation in 65% of BeS patients and patients with CBD, ELISPOT analysis detected IFN-gamma secretion in 80% of these subjects. Higher numbers of beryllium-specific cells in blood were also associated with the extent of alveolar inflammation, as measured by both bronchoalveolar lavage white blood cell and lymphocyte counts.

CONCLUSION

The frequency of beryllium-specific T cells in the blood of beryllium-exposed subjects may be a useful biomarker that helps discriminate between beryllium sensitization and progression to CBD.

摘要

背景

铍致敏是由工作场所接触铍引起的。一部分铍致敏(BeS)受试者会发展为慢性铍病(CBD),这是一种以CD4 + T细胞肺泡炎和肉芽肿性炎症为特征的疾病。血液中是否存在能够在不进行侵入性肺部检查的情况下区分CBD和铍致敏的生物标志物尚不清楚。

目的

本研究的目的是确定CBD患者血液中铍特异性T细胞的数量是否与BeS受试者不同。

方法

测定了33例CBD患者和18例BeS受试者血细胞中铍诱导的T细胞增殖和TH1型细胞因子分泌。

结果

我们在此证明,与BeS受试者和正常对照受试者相比,CBD患者血液中产生IFN-γ和IL-2的铍特异性CD4 + T细胞数量显著增加。相比之下,BeS患者和CBD患者之间在铍诱导的血液T细胞增殖方面没有差异。与血液铍淋巴细胞增殖试验相比,该试验在65%的BeS患者和CBD患者中检测到铍诱导的增殖,ELISPOT分析在80%的这些受试者中检测到IFN-γ分泌。血液中较高数量的铍特异性细胞也与肺泡炎症程度相关,通过支气管肺泡灌洗白细胞和淋巴细胞计数来衡量。

结论

铍暴露受试者血液中铍特异性T细胞的频率可能是一种有用的生物标志物,有助于区分铍致敏和向CBD的进展。

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