Role of mycobacteria in sarcoidosis immunopathogenesis

结节病是一种病因不明的疾病，病理特征为非干酪性肉芽肿。 最常见的累及肺、皮肤、淋巴结和眼睛。具有相似病理和证候的证候 结节病的免疫学特征，如慢性铍病、过敏性肺炎和 肺结核说明肉芽肿性疾病可能或可能具有感染性病原学。我们表演了 石蜡包埋结节病标本及对照标本中分枝杆菌的PCR检测 16S rRNA和rpoB。我们在60%的结节样肉芽肿中发现了分支杆菌核酸的证据。 而在所有对照中(P&lt；0.00002，卡方检验)。16S rRNA和rpoB的序列分析 扩增结果显示存在一种新的分枝杆菌，在基因上与结核分枝杆菌相似。 (99%的位置认同)。我们将研究范围扩大到包括10个冷冻结节病和10个对照组织。 来自范德比尔特大学和美国其他地区。我们确定了分枝杆菌的核 50%的冰冻结节病标本中含有酸性物质，而对照组中没有发现酸性物质(p&lt；0.0325，双尾费舍尔试验)。 最近，我们对结节病患者(n=10)和对照(n=9)外周血进行了ELISPOT分析 单个核细胞(PBMC)。我们在70.0%的结节病患者中发现了MTB katG多肽的免疫识别。 与阴性对照标本比较(P=0.01，ANOVA分析)。中环 假设结节病是一种对分枝杆菌感染的免疫学反应，在遗传上 易感宿主。我们已经组成了一个全国性的合作组织，包括国家犹太医学和研究组织 范德比尔特大学医学院和科罗拉多大学博尔德分校。该计划的目的是 合作是为了确定分枝杆菌是否在结节病的免疫发病机制中发挥作用。我们会 结合结节病和控制资源1)对结节病进行分子表征 肉芽肿使用致病分支杆菌的基因，2)比较T细胞特异性干扰素-γ 结节病患者向慢性阻塞性肺病患者、PPD对照人群和 结核分枝杆菌感染患者，3)使用原位杂交技术定位结核分枝杆菌 结节病种类，以便更好地了解宿主与病原体的相互作用。这些发现，将会 以独立和互补的方式评估分枝杆菌在结节病中的作用 免疫发病机制，可能会对结节病的未来治疗方式产生影响。

Sarcoidosis is a disease of unknown etiology, characterized pathologically by noncaseating granulomas which most commonly involve the lung, skin, lymph node and eyes. Syndromes with similar pathologic and immunologic features to sarcoidosis such as chronic beryllium disease, hypersensitivity pneumonitis, and tuberculosis illustrate that granulomatous diseases may or may have an infectious etiology. We performed PCR analysis of paraffin-embedded sarcoidosis and control specimens for the presence of Mycobacterium 16S rRNA and rpoB. We found evidence of mycobacterial nucleic acids in 60% of the sarcoid granulomas and in none of the controls (p<0.00002, chi square). Sequence analysis of the 16S rRNA and rpoB amplicons revealed the presence of a novel Mycobacterium, genetically similar to M. tuberculosis (MTB) (99% positional identity). We expanded our work to include ten frozen sarcoidosis and ten control tissues from Vanderbilt University and from other regions of the United States. We identified mycobacterial nucleic acid in 50% of frozen sarcoidosis specimens and in none of controls (p<0.0325, two-tailed Fisher's test). Most recently, we performed ELISPOT assays on sarcoidosis '(n=10) and control (n=9) peripheral blood mononuclear cells (PBMC). We found immune recognition of MTB katG peptides in 70.0% of the sarcoidosis specimens compared to none of the negative control specimens (p=0.01, ANOVA analysis). The central hypothesis is that sarcoidosis is an immunologic response to a mycobacterial infection in a genetically susceptible host. We have formed a national collaboration involving National Jewish Medical and Research Center, Vanderbilt University School of Medicine, and University of Colorado, Boulder. The purpose of the collaboration is to determine if mycobacteria have a role in sarcoidosis immunopathogenesis. We will combine the sarcoidosis and control resources 1) to perform molecular characterization of sarcoidosis granulomas using genes which speciate pathogenic mycobacteria, 2) to compare T-cell specific interferon-y production to mycobacterial peptides in sarcoidosis patients to CBD patients, a PPD- control population, and patients with M. tuberculosis infection, 3) to use in situ hybridization to localize mycobacteria within sarcoidosis species in order to better understand host-pathogen interactions. These findings, which will assess in an independent and complementary fashion the role of mycobacteria in sarcoidosis immunopathogenesis, may have an impact on future therapeutic modalities for sarcoidosis.