Pathophysiology of antigen 85 in patients with active tuberculosis: Antigen 85 circulates as complexes with fibronectin and immunoglobulin G
Pathophysiology of antigen 85 in patients with active tuberculosis: Antigen 85 circulates as complexes with fibronectin and immunoglobulin G
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DOI：
10.1128/iai.67.2.581-588.1999
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发表时间：
1999-02-01
影响因子：
3.1
通讯作者：
Godfrey, HP
中科院分区：
文献类型：
--
作者：
Bentley-Hibbert, SI;Quan, X;Godfrey, HP
抗原85(Ag85)复合蛋白是结核分枝杆菌的主要分泌产物，在感染的实验动物和人体内可诱导强烈的细胞和体液免疫应答。我们之前已经证明，纳克剂量的这些30到32 kDa的纤维连接蛋白结合蛋白通过T细胞纤维连接蛋白依赖的机制抑制局部迟发性超敏反应的表达。活动性肺结核患者的循环Ag85水平可能会升高，并可能在这些患者的全身性无能中发挥作用。为了验证这一假说，用基于单抗的斑点免疫结合试验检测了56名皮肤试验反应性已知的患者和对照组的血清和尿液中的Ag85。活动性肺结核患者的血清Ag85中位数水平比活动性禽分枝杆菌细胞内疾病或其他非结核肺病患者或健康对照组高50-150倍(P<；0.001)。活动性肺结核患者皮试阳性和阴性患者血清Ag85的中位数和范围均无显著差异。用具有适当特异性的抗Ag85单抗可将活动性禽分枝杆菌病与结核分枝杆菌病区分开来。无论血清中Ag85水平如何，均未检测到尿中Ag85的增加。血清的层析分析和免疫沉淀研究表明，这些患者的血清中存在与纤维连接蛋白或免疫球蛋白G(IGC)络合的Ag85。不到20%的活动性肺结核患者血清中可见无复杂循环的Ag85。因此，在活动性肺结核患者中，Ag85可能主要以与血浆纤维连接蛋白和免疫球蛋白的复合体的形式循环，而不是以游离形式存在。Ag85与血浆蛋白复合体的存在可能是其缺乏尿液清除量的原因。
Antigen 85 (Ag85) complex proteins are major secretory products of Mycobacterium tuberculosis and induce strong cellular and humoral immune responses in infected experimental animals and human beings. We have previously shown that nanogram doses of these 30- to 32-kDa fibronectin-binding proteins inhibit local expression of delayed hypersensitivity by a T-cell fibronectin-dependent mechanism. Circulating levels of Ag85 might be expected to be elevated in patients with active tuberculosis and possibly to play a role in systemic anergy in these patients. To test this hypothesis, Ag85 was measured in serum and urine by a monoclonal antibody-based dot immunobinding assay in 56 patients and controls with known skin test reactivity. Median serum Ag85 levels were 50- to 150-fold higher in patients with active tuberculosis than in patients with active M. avium-intracellulare disease or other nontuberculous pulmonary disease or in healthy controls (P < 0.001). The median and range of serum Ag85 in patients with active tuberculosis was not significantly different between skin test-positive and -negative subjects. Patients with active M. avium disease could be distinguished from those with disease due to M. tuberculosis by monoclonal anti-Ag85 antibodies of appropriate specificities. No increases in urinary Ag85 were detected in any patient, regardless of the Ag85 level in serum. Chromatographic analysis and immunoprecipitation studies of serum revealed that Ag85 existed in the serum of these patients complexed to either fibronectin or immunoglobulin G (Igc). Uncomplexed circulating Ag85 was demonstrable in serum from fewer than 20% of patients with active tuberculosis. In patients with active tuberculosis, Ag85 is therefore likely to circulate primarily as complexes with plasma fibronectin and IgG rather than in unbound form. The existence of Ag85 complexes with plasma proteins would account for its lack of urinary clearance.