Role of mycobacteria in sarcoidosis immunopathogenesis

结节病是一种病因不明的疾病，其病理特征是非干酪化性肉芽肿 其最常见地涉及肺、皮肤、淋巴结和眼睛。同时伴有类似的病理和 结节病的免疫学特征，如慢性铍病，过敏性肺炎， 结核病说明肉芽肿性疾病可能或可能具有感染性病因。我们进行 石蜡包埋的结节病和对照标本中分枝杆菌的PCR分析 16 S rRNA和rpoB。我们在60%的结节病肉芽肿中发现了分枝杆菌核酸的证据 而在对照组中没有（p<0.00002，卡方）。16 S rRNA和rpoB的序列分析 扩增子显示存在一种新的分枝杆菌，遗传上类似于M.结核病（MTB） (99%位置同一性）。我们扩大了我们的工作，包括十个冷冻结节病和十个对照组织 来自范德比尔特大学和美国其他地区。我们鉴定了分枝杆菌核酸 在50%的冷冻结节病标本中，没有一个对照组中存在酸（p<0.0325，双尾Fisher检验）。 最近，我们对结节病（n=10）和对照（n=9）外周血进行了ELISPOT检测 单核细胞（PBMC）。我们发现在70.0%的结节病中MTB katG肽被免疫识别 与阴性对照标本相比，阴性对照标本中无（p=0.01，ANOVA分析）。中央 假设结节病是一种对分枝杆菌感染的免疫反应， 易感宿主我们已经建立了一个全国性的合作， 中心，范德比尔特大学医学院和科罗拉多大学，博尔德。的目的 合作的目的是确定分枝杆菌是否在结节病免疫发病机制中发挥作用。我们将 将结节病和控制资源联合收割机1）进行结节病的分子表征 使用致病性分枝杆菌的基因，2）比较T细胞特异性干扰素-γ 在结节病患者至CBD患者中产生分枝杆菌肽，PPD对照群体，和 患者M.结核感染，3）使用原位杂交定位结核杆菌内 结节病物种，以更好地了解宿主-病原体相互作用。这些发现将 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.