Abstract and Introduction
Purpose of review: To describe the most recent epidemiologic, molecular and immunologic literature related to the role of infectious antigens in sarcoidosis pathogenesis, with a focus upon Mycobacterium and Proprionibacterium species.
Recent findings: Recent studies of successful molecular analysis for and humoral immunity to mycobacterial antigens from sarcoidosis patients have renewed interest in a potential role of mycobacteria in sarcoidosis. One study provided molecular and immunologic evidence for mycobacteria among sarcoidosis subjects from the United States. These studies, while preliminary, provide the groundwork for more in-depth studies of the potential role of mycobacteria in sarcoidosis pathogenesis. Proprionibacteria have also been proposed as a cause of sarcoidosis; a study of the detection of Proprionibacterium species nucleic acids throughout the lung of sarcoidosis and control subjects, however, suggests that these organisms are less likely to be causal.
Summary: While the studies to date do not fulfill Koch's postulates, they do add further support to the hypothesis that infectious antigens, particularly those from mycobacteria, may have a causal role in some sarcoidosis cases. In future studies that purport to show an association of microbial antigen(s) with sarcoidosis, investigation of genetic risk factors contributing to risk will be important, in order to explain why some patients are found to have an association with microbial antigens and others are not.
Sarcoidosis is a disease of unknown cause, characterized pathologically by noncaseating granulomas which most commonly involve the lung, skin, lymph nodes and eyes. Syndromes with similar pathologic and immunologic features to sarcoidosis, such as chronic beryllium disease, hypersensitivity pneumonitis and tuberculosis, illustrate that granulomatous disease may or may not have an infectious cause. While no infectious agent has been identified within sarcoidosis specimens, there are immunologic and clinical aspects of sarcoidosis that suggest an infectious origin. Sarcoidosis immunology reflects Th-1 cytokine expression, which is based upon antigen-specific T-cell responses. Studies of T-cell receptor gene expression in sarcoidosis patients reveal oligoclonal collections of αβ+ CD4+ T cells at sites of granulomatous inflammation, consistent with a MHC-restricted antigen-driven process.[5,6,7] Another feature is the transmissibility of sarcoidosis. 'Donor-acquired sarcoidosis' is defined as the development of sarcoidosis in presumably naive (nonsarcoidosis) transplant recipients who have received tissues or organs from donors who were known or suspected to have active sarcoidosis.[8,9] Studies[10,11,12,13] of the development of sarcoidosis granulomas in animals that received tissue from sarcoidosis patients exist. These cases strengthen the view that sarcoidosis is caused by a transmissible agent, perhaps of infectious origin. Sarcoidosis has pathologic, immunologic and epidemiologic features most similar to mycobacterial infections, particularly tuberculosis.
Curr Opin Pulm Med. 2006;12(5):359-363. © 2006 Lippincott Williams & Wilkins