既往有肺外结核的成年人中CD4+淋巴细胞减少及先天性免疫反应降低。

Decreased CD4+ lymphocytes and innate immune responses in adults with previous extrapulmonary tuberculosis.

作者信息

Antas Paulo R Z, Ding Li, Hackman Judith, Reeves-Hammock Linda, Shintani Ayumi K, Schiffer Joshua, Holland Steven M, Sterling Timothy R

机构信息

Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2605, USA.

出版信息

J Allergy Clin Immunol. 2006 Apr;117(4):916-23. doi: 10.1016/j.jaci.2006.01.042.

DOI:10.1016/j.jaci.2006.01.042

PMID:16630952

Abstract

BACKGROUND

CD4+ lymphocytes control Mycobacterium tuberculosis infection through cytokine-mediated macrophage activation. Extrapulmonary tuberculosis is presumably a marker of immunodeficiency, but cytokine responses have not been well studied in such patients.

OBJECTIVE

Assess immune defects in persons with previous extrapulmonary tuberculosis.

METHODS

In vitro cytokine responses of PBMCs from HIV-seronegative adults with previous extrapulmonary tuberculosis (n = 10) were compared with responses from persons with previous pulmonary tuberculosis (n = 24) and latent M tuberculosis infection (n = 30) in a case-control study.

RESULTS

Patients and controls did not differ according to age, sex, race, or monocytes. The median time between tuberculosis diagnosis and study entry was 72 and 122 weeks in extrapulmonary and pulmonary patients, respectively (P = .2). Median CD4+ counts were 660, 814, and 974 lymphocytes/mm3 in extrapulmonary, pulmonary, and latently infected patients, respectively (P = .03). At 48 hours, median unstimulated cytokine levels were uniformly lower in extrapulmonary patients than both sets of controls. These differences persisted after controlling for CD4+ count by linear regression analysis. Despite lower unstimulated levels, median TNF-alpha response was higher in patients with extrapulmonary and pulmonary tuberculosis than latently infected persons after stimulation with PHA 1% (P = .006) and PHA+IL-12 (1 ng/mL; P = .02); IL-10 remained low in patients with extrapulmonary tuberculosis after the same stimuli (P = .04 and .06, respectively). There was no primary immunodeficiency in the IL-12/23-IFN-gamma axis.

CONCLUSION

HIV-seronegative adults with previous extrapulmonary tuberculosis had lower CD4+ lymphocytes and unstimulated cytokine production. This suggests a subtle abnormality in innate immune function.

CLINICAL IMPLICATIONS

These characteristics could identify persons at risk for severe tuberculosis manifestations.

摘要

背景

CD4+淋巴细胞通过细胞因子介导的巨噬细胞活化来控制结核分枝杆菌感染。肺外结核可能是免疫缺陷的一个标志，但此类患者的细胞因子反应尚未得到充分研究。

目的

评估既往有肺外结核患者的免疫缺陷情况。

方法

在一项病例对照研究中，将既往有肺外结核的HIV血清阴性成年人（n = 10）外周血单个核细胞（PBMC）的体外细胞因子反应与既往有肺结核（n = 24）和潜伏性结核分枝杆菌感染（n = 30）患者的反应进行比较。

结果

患者和对照组在年龄、性别、种族或单核细胞方面无差异。肺外结核和肺结核患者从结核病诊断到研究入组的中位时间分别为72周和122周（P = 0.2）。肺外结核、肺结核和潜伏感染患者的CD4+细胞计数中位数分别为660、814和974个淋巴细胞/mm3（P = 0.03）。48小时时，肺外结核患者未受刺激的细胞因子水平中位数均低于两组对照组。通过线性回归分析控制CD4+细胞计数后，这些差异仍然存在。尽管未受刺激的水平较低，但在用1%PHA和PHA + IL-12（1 ng/mL）刺激后，肺外结核和肺结核患者的TNF-α反应中位数高于潜伏感染患者（P = 0.006和P = 0.02）；在相同刺激后，肺外结核患者的IL-10水平仍然较低（分别为P = 0.04和0.06）。IL-12/23 - IFN-γ轴不存在原发性免疫缺陷。