Molecular Analysis of Sarcoidosis Tissues for Mycobacterium Species DNA

Wonder Puryear Drake, Zhiheng Pei, David T. Pride, Robert D. Collins, Timothy L. Cover, Martin J. Blaser


Emerging Infectious Diseases. 2002;8(11) 

In This Article

Abstract and Introduction

We performed polymerase chain reaction analysis, for Mycobacterium species 16S rRNA, rpoB, and IS6110 sequences, on 25 tissue specimens from patients with sarcoidosis and on 25 control tissue specimens consisting of mediastinal or cervical lymph nodes and lung biopsies. Mycobacterium species 16S rRNA sequences were amplified from 12 (48%) rpoB sequences and from 6 (24%) of the sarcoidosis specimens. In total, 16S rRNA or rpoB sequences were amplified from 15 sarcoidosis specimens (60%) but were not detected in any of the control tissues (p=0.00002, chi square). In three specimens, the sequences resembled Mycobacterium species other than M. tuberculosis. All specimens with sequences consistent with M. tuberculosis were negative for IS6110. We provide evidence that one of a variety of Mycobacterium species, especially organisms resembling M. tuberculosis, is found in most patients with sarcoidosis.

Sarcoidosis is a multisystem inflammatory disease that mainly affects lymph nodes and pulmonary tissues and is characterized by noncaseating granulomata in affected organs[1]. Although the cause of sarcoidosis remains unknown, several microorganisms have been proposed as possible etiologic agents, including bacteria (Borrelia burgdorferi, Proprionibacterium acnes, and Mycobacterium species) and viruses (Human herpesvirus 8, Epstein-Barr virus, Cytomegalovirus, and Coxsackie B)[2]. Metals (beryllium and zirconium), minerals (talc and clay), and organic substances (pine tree pollen) have also been proposed as etiologic agents[2]. Efforts to identify an infectious agent for sarcoidosis using methods such as histologic staining and routine microbial culture have been unsuccessful. Polymerase chain reaction (PCR) analysis for microbial DNA serves as an alternative method for identifying infectious agents. PCR was used to identify the etiologic agents of bacillary angiomatosis (Bartonella henselae)[3] and Whipple's disease (Tropheryma whippelii)[4]. Because of the substantial pathologic[5], immunologic[6], epidemiologic[7], and clinical similarities[8,9] between sarcoidosis and infections caused by Mycobacterium species (particularly tuberculosis), we analyzed tissue specimens from patients with sarcoidosis for evidence of mycobacterial genes. The results of previous studies have been inconclusive; some investigators were unable to demonstrate mycobacterial DNA in sarcoid lesions[10,11], whereas others have amplified mycobacterial DNA of different species[12,13]. We examined sarcoidosis and control paraffin-embedded pulmonary, mediastinal, and cervical tissue specimens for Mycobacterium species 16S rRNA, rpoB, and IS6110 sequences.