Mycobacterium tuberculosis antigen 85A induces Th-1 immune responses in systemic sarcoidosis
Mycobacterium tuberculosis antigen 85A induces Th-1 immune responses in systemic sarcoidosis
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DOI：
10.1007/s10875-007-9080-4
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发表时间：
2007-07-01
影响因子：
9.1
通讯作者：
Drake, Wonder Puryear
中科院分区：
文献类型：
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作者：
Hajizadeh, Rana;Sato, Hiroe;Drake, Wonder Puryear
结节病是一种病因不明的肉芽肿性疾病，以Th-1免疫表型为特征。虽然已经检测到结节病受试者对分枝杆菌蛋白的体液免疫应答，但尚未报道能够在结节病受试者中诱导细胞免疫应答的分枝杆菌抗原。我们使用酶联免疫斑点试验来评估25名结节病患者、22名PPD-（纯化蛋白衍生物）健康志愿者和16名PPD+健康受试者的外周血单核细胞对结核分枝杆菌分枝菌酰转移酶（抗原85 A）的识别。在25例结节病受试者中的15例中观察到对Ag 85 A全蛋白的反应性，与之相比，22例PPD-受试者中的2例（p=0.0006，Fisher精确检验）和16例PPD+受试者中的14例（p=0.084，Fisher精确检验）。抗HLA-DR单克隆抗体抑制识别。除了免疫识别的Ag 85 A全蛋白，肽图谱的研究确定了四个免疫原性Ag 85 A肽，诱导Th-1免疫反应，在个别结节病的主题，这表明，多个表位从分枝杆菌蛋白质可能有一个作用，在结节病的免疫发病机制。
Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th-1 immunophenotype. Although humoral immune responses by sarcoidosis subjects to mycobacterial proteins have been detected, mycobacterial antigens capable of inducing cellular immune responses in sarcoidosis subjects have not been reported. We used the enzyme-linked immunospot assay to assess for recognition of the Mycobacterium tuberculosis mycolyl transferase, Antigen 85A, by peripheral blood mononuclear cells from 25 sarcoidosis subjects, 22 PPD- (purified protein derivative) healthy volunteers, and 16 PPD+ healthy subjects. Reactivity to Ag85A whole protein was observed in 15 of 25 sarcoidosis subjects compared to 2 of 22 PPD- subjects (p=0.0006, Fisher's exact test) and to 14 of 16 PPD+ subjects (p=0.084, Fisher's exact test). Monoclonal antibody against HLA-DR inhibited recognition. In addition to immune recognition of Ag85A whole protein, peptide-mapping studies identified four immunogenic Ag85A peptides, which induced Th-1 immune responses in individual sarcoidosis subjects, suggesting that multiple epitopes from a mycobacterial protein may have a role in sarcoidosis immunopathogenesis.