COPD and autoimmunity
Over the past few years, researchers have begun to hypothesize a link between COPD and autoimmunity; developing new models for the inflammation seen with the disease. Can big data analytics provide evidence to support this concept?
A long-established condition
As one of the top five causes of death worldwide, we’d like to think we have a good understanding of how chronic obstructive pulmonary disease, or COPD, works.1 Broadly encompassing chronic bronchitis with or without emphysema, the condition has been known for decades to involve neutrophils and macrophages as the vital innate immune cells that underlie its pathobiology. But while chronic exposure to smoke promotes the recruitment of these cells into the lung, in recent years a distinct role for adaptive immunity in COPD has become apparent.2
COPD and autoimmune inflammation
In emphysema, studies have demonstrated a clear role for the recruitment and activation of pathogenic lymphocytes and lung antigen-presenting cells. Raised numbers of activated Th1 and Th17 cells have been found to be associated with smoke-induced lung inflammation, while increased production of the cytokines IFN-γ and IL-17, correlates with disease severity. These intriguing findings have led to the creation of a new concept: in vulnerable individuals, cigarette-smoke exposure may initiate chronic inflammatory memory T-cell responses that can last beyond the acute exposure period. Researchers believe that this model of autoimmune inflammation could vindicate the enduring lung inflammation seen in COPD, regardless of smoking cessation.2
Big data analytics
Because of results such as these, Georgia State University and Vanderbilt University Medical Center embarked on a large-scale project to examine human genome information stored in Vanderbilt’s DNA biobank. The researchers analyzed the association between genetic variants in COPD and clinical phenotypes, or physical factors such as disease history, to gain a greater understanding of the pathogenesis of COPD. Genetic data stored in the biobank and linked to anonymized electronic health records was used by the analysts to perform a phenome-wide association study (PheWAS) of COPD-associated single nucleotide polymorphisms (SNPs) that were discovered in previous genome-wide association studies.3,4
Novel genetic links
“We’re trying to figure out whether we can diagnose or prognose this disease earlier to prevent it,” said Dr. Xiangming Ji, assistant professor in the Byrdine F. Lewis College of Nursing and Health Professions at Georgia State. “People are genetically very similar, but a major difference is because of this SNP…so some people with a specific SNP are more prone to get this disease.3 The study revealed that one of the previously identified COPD-related SNPs, rs2074488, is also associated with a number of autoimmune diseases, including type 1 diabetes, rheumatoid arthritis and bronchiectasis, indicating a genetic link between autoimmune disease and COPD. These results strongly support the previous hypothesis that an autoimmune biologic mechanism underpins the risk of COPD, while simultaneously highlighting the potential for big data analytics in disease discovery.3,4
Looking to the future
The researchers involved in this study are hopeful that future investigations will research how normal SNPs, such as those linked to metabolic pathways or nutrient receptors, are associated with COPD. They also believe the results from the study could provide valuable insights into potential drug repurposing; a critical discovery in the current COPD landscape.3
- Burden of COPD. Available at: https://www.who.int/respiratory/copd/burden/en/. Accessed: October 2019.
- Kheradmand F et al. Expert Rev Clin Immunol 2012; 8(3): 285–292.
- Science Daily. Autoimmunity plays role in development of COPD. Available at: https://www.sciencedaily.com/releases/2018/08/180816143046.htm. Accessed: October 2019.
- Xiangming J et al. Am J Respir Cell Mol Biol 2018; 58(6): 777–779.
RESP-41991 November 2019