Translational Research in Sarcoidosis: Addressing Health Disparities
EPI222 Final Project Writeup
Sarcoidosis is a disease of systemic granulomatous inflammation without a known cause. It affects the lungs in 90% of patients, but can affect any organ system (1, 2). A key component of sarcoidosis-related inflammation are CD4+ T cells that make the cytokine IFN-γ, therefore the immune aspects of the disease has been a significant focus of research (3). Sarcoidosis also has variability in incidence and prevalence based on race age (peak between 30-60), sex (incidence of 5.9/100,000 in men and 6.3/100,000 person-years in women), and race (4). African American have greater incidence of the disease compared to Whites (5, 6). African Americans also have greater rates of fibrosis at diagnosis, greater number of organs involved, and are more often prescribed immunosuppressive treatment (74.5% of African Americans treated versus 55.1% Whites) (7). Among those treated, African Americans are more likely to be prescribed steroids compared to steroid-sparing immunosuppressive treatments (69.9% vs. 46%) (7). This likely reflects the fact that African Americans have decreased access to care since steroids require less monitoring than drugs such as methotrexate or azathioprine, but have greater risk of side effects. The reasons for these disparities are unclear and because the disease has strong immune mechanisms and there is a much larger incidence in African Americans compared to Whites, it is an on-going question as to whether African Americans have higher risk factors due to biologic factors such as ancestry/genetics or if is due to social and economic factors. For example, a recent publication looked at the incidence of sarcoidosis geographically and found a general trend that greater distance from the equator increases the incidence of sarcoidosis (7). Given that sarcoidosis also affects vitamin D metabolism and vitamin D affects the immune system, there are theories that sarcoidosis could be related to skin color and vitamin D and lower levels of vitamin D. These biologic explanations risk overlooking key socio-economic aspects that are likely causing the increased incidence and the disparities in the disease. This course has broadened my views of the non-biologic factors affecting sarcoidosis patients and has made me interpret data from my own research carefully in the context of race. For example, in my own research, I have measured levels of serum inflammatory proteins (chemokines) to determine how they are associated with specific sarcoidosis outcomes. I measured three proteins that are induced by IFN-γ, CXCL9, CXCL10, and CXCL11. I found that all three chemokines were increased in sarcoidosis patient relative to healthy controls. These proteins also were negatively associated with sarcoidosis outcome. In my models, I controlled for self-identified race. I also found that CXCL11 was the only chemokine that differed by race, specifically that in both sarcoidosis and healthy control subjects, African Americans had higher levels of CXCL11, which was not true of CXCL9 or CXCL10. An interpretation of this could be that African Americans have higher levels of CXCL11 related to the underlying genetics/ancestry, but this could also be due to the fact that we had few African Americans in the cohort (15%), therefore there could be selection bias, especially due to the fact that there are several other reasons why African Americans could have higher levels of these chemokines related to environmental and social factors. Fortunately, I interpreted these data with caution and advised that further studies of these chemokines in a more diverse population is necessary.
References:
[1] Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. The New England journal of medicine. 2007;357(21):2153-65. doi: 10.1056/NEJMra071714.
[2] Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Muller-Quernheim J. Sarcoidosis. Lancet (London, England). 2014;383(9923):1155-67. doi: 10.1016/S0140-6736(13)60680-7 [doi].
[3] Agostini C, Meneghin A, Semenzato G. T-lymphocytes and cytokines in sarcoidosis. Current opinion in pulmonary medicine. 2002;8(5):435-40.
[4] Henke CE, Henke G, Elveback LR, Beard CM, Ballard DJ, Kurland LT. The epidemiology of sarcoidosis in Rochester, Minnesota: a population-based study of incidence and survival. American journal of epidemiology. 1986;123(5):840-5. doi: 10.1093/oxfordjournals.aje.a114313.
[5] Baughman RP, Field S, Costabel U, Crystal RG, Culver DA, Drent M, Judson MA, Wolff G. Sarcoidosis in America. Analysis Based on Health Care Use. Annals of the American Thoracic Society. 2016;13(8):1244-52. doi: 10.1513/AnnalsATS.201511-760OC.
[6] Rybicki BA, Major M, Popovich J, Jr., Maliarik MJ, Iannuzzi MC. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. American journal of epidemiology. 1997;145(3):234-41.
[7] Judson MA, Boan AD, Lackland DT. The clinical course of sarcoidosis: presentation, diagnosis, and treatment in a large white and black cohort in the United States. Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG. 2012;29(2):119-27.