From the Guidelines
The exact cause of sarcoidosis remains unknown, though it appears to result from an exaggerated immune response to an unknown antigen, with various agents such as infective agents, chemicals, and environmental factors suggested as potential triggers. When exposed to these triggers, the immune system overreacts, leading to inflammation and the formation of granulomas (clusters of inflammatory cells) in various organs, most commonly the lungs and lymph nodes 1. Several factors are believed to contribute to sarcoidosis development, including genetic predisposition, as the condition sometimes runs in families and is more common in certain ethnic groups. Environmental factors such as exposure to certain bacteria, viruses, chemicals, or dust particles may trigger the immune response, with working on the World Trade Centre debris after 9.11.2001 being associated with the development of sarcoidosis 1.
Some key points to consider in the development of sarcoidosis include:
- Genetic predisposition, with the condition sometimes running in families and being more common in certain ethnic groups
- Environmental factors, such as exposure to certain bacteria, viruses, chemicals, or dust particles, which may trigger the immune response
- Occupational exposures, particularly in firefighters, military personnel, and healthcare workers, which have been associated with higher risk
- An imbalance in T-cell activity, with increased T-helper cells driving the inflammatory response and granuloma formation, and the release of IL2, followed by a non-caseating granuloma 1
- The involvement of TH1 cytokines, such as interferon, and tumour necrosis factor (TNF), as well as B cell hyperreactivity and immunoglobulin production 1
While researchers have made progress in understanding the mechanisms of sarcoidosis, the specific combination of genetic and environmental factors that causes the disease in each individual remains elusive, making it difficult to prevent or predict who will develop the condition 1.
From the Research
Causes of Sarcoidosis
- The exact cause of sarcoidosis is unknown 2, 3, 4.
- It is believed to result from an overexuberant T cell-mediated immune response to an unknown antigen 2.
- The prevailing hypothesis is that various unidentified, likely poorly degradable antigens of either infectious or environmental origin could trigger an exaggerated immune reaction in genetically susceptible hosts 3.
- Genetic factors affect not only the risk of developing sarcoidosis but also the disease course, which is highly variable and difficult to predict 4.
- The disease develops in genetically predisposed individuals with exposure to an as-yet unknown antigen 4.
Immune Response and Granuloma Formation
- Sarcoidosis is characterized by the formation of immune granulomas in involved organs 3.
- The inflammatory response in sarcoidosis is induced by specific antigens, possibly including self-antigens, which is consistent with an autoimmune involvement 4.
- An amplified cellular immune response ensues, leading to granuloma formation and fibrosis 2.
- The microenvironment is suffused in proinflammatory cytokines and growth factors that promote cell attraction, adhesion, permeability changes, further cytokine production, and release 2.
Genetic Predisposition
- Genetic factors play a role in the development of sarcoidosis 3, 4.
- Polymorphisms have been identified as associated with treatment response, suggesting a step towards personalized medicine 5.
- Future research should focus on the role for pharmacogenetic and phenotypic predictors of treatment response and toxicity 5.