Potential infectious agents in the pathogenesis of sarcoidosis

Year 2016 has brought new reports on a possible participation of infectious agents in the pathogenesis of sarcoidosis. Chinese scientists have published in the ‘PLoS One’ journal the results of a meta-analysis suggesting a possible contribution of Mycobacteria in the development of the disease. On the other hand, an international team of experts have published in the ‘American Journal of Respiratory Cell and Molecular Biology’ the results of an experiment indicating a contribution of Propionibacterium acnes infection in the pathogenesis of sarcoidosis.

Sarcoidosis, also known as Boesnier, Boeck and Schaumann disease, is a systemic granulomatous disease affecting mainly lungs and lymphatic nodes but also other organs like subcutaneous tissue, heart, eyes and bones. Its etiology is still undiscovered; it is suggested there is a contribution of genetic, autoimmune and environmental factors, including infectious microorganisms.

Multidirectional researches on etiology of sarcoidosis postulate, that it is a multifactorial disease, in pathogenesis of which, bacteria like Mycoplasma, Borrelia, Propionibacterium, Corynebacterium or Mycobacterium may play some vital role, as well as few viruses including HSV or EBV [1,2], though, there are no undeniable evidences to prove the infectious mechanism in the pathogenesis of sarcoidosis. Still, some newest papers published in 2016 shed a new light on this issue.

In the meta-analysis published by Chinese scientists in ‘PLoS One’ in August 2016, 13 papers from 1990-2015 with 733 patients suffering from sarcoidosis were analysed. Researchers confirmed, that there is a correlation between infections caused by Mycobacteria, especially M. tuberculosis, and the development of the disease. However, they suggest, that this correlation is caused by immune cell-mediated response to soluble antigens of M. tuberculosis, rather than by whole microorganisms’ presence [3].

Similar conclusions were shown in the article about pulmonary sarcoidosis published in ‘Wiadomości Lekarskie’. Although the author of the paper indicates, that in many publications a response of T lymphocytes to mycobacterial antigens in patients with sarcoidosis is emphasized, there are still no direct evidences in the literature of a role of living Mycobacteria in the pathogenesis of Besnier, Boeck and Schaumann disease [4].

The international team of resarchers from the United States, the Netherlands and Japan conducted an experiment where P. acnes (responsible, among others, for acne vulgaris development) was isolated from a patient suffering from sarcoidosis. Subsequently, a suspension of the agent was prepared and administered intratracheally to a mouse with a genetic deficit of MYD88 protein (which takes part in antibacterial immunity in mice) and CYBB (a heavy chain of b-245 cytochrome responsible for reactive oxygen species synthesis). Granulomatous changes (similar to those in patients with sarcoidosis) have developed in mouse’s lungs. This result indicates, that there may be a genetic predisposition to the development of the disease under influence of some infectious agents. Scientists have published their conclusions in the ‘American Journal of Respiratory Cell and Molecular Biology’ in August [5].

In April 2016, Brazilian scientists have described a case of a patient with co-existing hepatitis C and sarcoidosis. Although the authors stress, that it is only a case study, whose results can be not fully credible, they made an interesting observation – they managed to isolate and grow hepatitis C virus from subcutaneous nodules formed because of sarcoidosis. The relation between both diseases in this patient requires further studies though [6].

The results of the studies described are not crucial if talking about a possible infectious pathogenesis of sarcoidosis, however, they indicate that infectious etiology may co-exist with a genetic predisposition to develop a specific immune response which triggers formation of the granulomas in tissues affected by sarcoidosis. Further studies about the role of Mycobacteria and Propionibacteria in development of Besnier, Boeck and Schaumann disease are promising in particular, although a list of microorganisms that should be examined in this regard is open.

Written by: Marcin Kulczyński, Michał Łuniewski, Justyna Markowicz-Roman

Sources:
1. Dubaniewicz A., Sarkoidoza – choroba o wielu twarzach, Forum Medycyny Rodzinnej, 1 (2009), 27-41
2. Grzelewska-Rzymowska I., Sarkoidoza – choroba ogólnoustrojowa, Alergia, 2 (2012), 23-31
3. Fang C., Huang H., Xu Z., Immunological Evidence for the Role of Mycobacteria in Sarcoidosis: A Meta-Analysis, PLoS One, 11 (2016), access on 13.11.2016 via PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27479700
4. Kempisty A., Pulmonary sarcoidosis – clinical features, diagnosis and treatment, Wiadomości Lekarskie, 69 (2016), 156-161
5. Werner J.L., Escolero S.G., Hewlett J.T. et al., Induction of Pulmonary Granuloma Formation by Propionibacterium acnes is regulated by MyD88 and Nox2, American Journal of Respiratory Cell and Molecular Biology, 2016, access on 13.11.2016 via PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27607191
6. Pereira E.G., Guimarães T.F., Bottino C.B. et al., Sarcoidosis and chronic hepatitis C: treatment with prednisone and colchicine, Anais Brasileiros de Dermatologia, 91 (2016), 231-234


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