Yamada Tetsuo, Eishi Yoshinobu, Ikeda Satoshi, Ishige Ikuo, Suzuki Takashige, Takemura Tamiko, Takizawa Touichiro, Koike Morio
Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
J Pathol. 2002 Dec;198(4):541-7. doi: 10.1002/path.1243.
Sarcoidosis is a systemic granulomatous disease of unknown aetiology. Many genomes of Propionibacterium acnes and P. granulosum have been detected in lymph nodes from patients with sarcoidosis. In situ localization of propionibacterial genomes in sarcoid lymph nodes may help to establish an aetiological link between sarcoidosis and these indigenous bacteria. Formalin-fixed and paraffin-embedded biopsy samples of lymph nodes from nine patients with sarcoidosis, nine patients with tuberculosis, and nine patients with non-specific lymphadenitis as controls were examined by quantitative real-time PCR (QPCR) for P. acnes and by in situ hybridization (ISH) that used catalysed reporter deposition (CARD) for signal amplification with digoxigenin-labelled oligonucleotide probes that complemented 16S rRNA of P. acnes. The signals per 250 micro m(2) of tissue sections were counted from inside and outside the granulomas of sarcoidosis and tuberculosis and from control lymph nodes. The number of genomes by QPCR was examined for correlation with the mean signal count by ISH with CARD. In sarcoid samples, one or several signals were detected in the cytoplasm of some epithelioid cells in granulomas and of many mononuclear cells around granulomas. The mean signal counts were higher (p < 0.001) in granulomatous areas than in other areas of sarcoid lymph nodes. Even in their non-granulomatous areas, counts were higher than in granulomatous areas (p = 0.0023) and non-granulomatous areas (p < 0.001) of tuberculous lymph nodes and control lymph nodes (p = 0.0071). Correlation between the results by QPCR and ISH with CARD was significant (r = 0.86, p < 0.001). The accumulation of P. acnes genomes in and around sarcoid granulomas suggests that this indigenous bacterium may be related to the cause of granulomatous inflammation in sarcoidosis.
结节病是一种病因不明的全身性肉芽肿性疾病。在结节病患者的淋巴结中已检测到许多痤疮丙酸杆菌和颗粒丙酸杆菌的基因组。结节病淋巴结中丙酸杆菌基因组的原位定位可能有助于建立结节病与这些本土细菌之间的病因学联系。通过定量实时PCR(QPCR)检测9例结节病患者、9例结核病患者和9例非特异性淋巴结炎患者(作为对照)的福尔马林固定石蜡包埋淋巴结活检样本中的痤疮丙酸杆菌,并通过原位杂交(ISH)检测,ISH使用催化报告沉积(CARD)进行信号放大,采用地高辛标记的寡核苷酸探针,该探针与痤疮丙酸杆菌的16S rRNA互补。从结节病和结核病肉芽肿的内部和外部以及对照淋巴结中,每250μm²组织切片计数信号。通过QPCR检测基因组数量,并与使用CARD的ISH的平均信号计数进行相关性分析。在结节病样本中,在肉芽肿中的一些上皮样细胞的细胞质以及肉芽肿周围的许多单核细胞中检测到一个或几个信号。肉芽肿区域的平均信号计数高于结节病淋巴结的其他区域(p < 0.001)。即使在其非肉芽肿区域,计数也高于结核性淋巴结的肉芽肿区域(p = 0.0023)和非肉芽肿区域(p < 0.001)以及对照淋巴结(p = 0.0071)。QPCR结果与使用CARD的ISH结果之间的相关性显著(r = 0.86,p < 0.001)。痤疮丙酸杆菌基因组在结节病肉芽肿内和周围的积累表明,这种本土细菌可能与结节病肉芽肿性炎症病因有关。