While researchers are still digging for answers on exactly what causes over 90 autoimmune diseases, there are certain risk factors known to affect immune tolerance, and therefore lead to the development of autoimmune conditions.
Keep in mind that while simply falling into one or more of these categories may increase your susceptibility, it does not mean you’re destined to develop a disorder.
Overall, 78% of people affected by autoimmune disease are female (1). Regarding specific conditions, up to 95% of systemic lupus erythematosus (SLE) and Sjogren’s syndrome patients are female (2). Other conditions like arthritis and multiple sclerosis occur in females around 60% more than in males (2).
Factors that differ between sexes like the X chromosome, reproductive function, hormones, immune responses, effects of environmental agents, and organ vulnerability could all have a hand in the higher autoimmune disease prevalence in females.
Certain disorders, such as lupus and multiple sclerosis (MS), tend to run in families (3, 4). If you have relatives with autoimmune disease, then you are more likely to develop a condition yourself (though not necessarily the same one).
Having a genetic predisposition towards autoimmunity means that your risk is higher due to an inherited genetic variation – one that may impact immune response (5). The way that particular gene is expressed can be altered via the epigenome – a layer of chemical tags that sits on top of your DNA (6).
When environmental triggers – such as toxic chemicals, infections or other physical traumas, intestinal dysbiosis, or dietary factors (7) – interact with the epigenome, they have the ability to activate or deactivate parts of the genome through complex chemical reactions.
Further study on the epigenome is needed, however the field of epigenetics highlights the critical role our lifestyle plays in either generating or preventing disease.
When you already exhibit one autoimmune disease, you’re at risk to develop more.
An accumulation of three or more autoimmune conditions is called Multiple Autoimmune Syndrome (MAS), which is seen in roughly 25% of patients (11).
It is common for individuals with certain conditions like celiac disease, rheumatoid arthritis, multiple sclerosis, Hashimoto’s, or Sjogren’s to exhibit MAS. The reason is unknown, but it is likely due to a combination of genetics and environmental factors.
Given that roughly 35% of the global population (13) and 72% of adults in the U.S. are overweight or obese (14), it is critical that we recognize the relationship between obesity and other chronic conditions like autoimmune disease.
Excess weight is associated with over ten autoimmune diseases and may be implicated in others (13). It has been found to increase the risk of developing autoimmune conditions like rheumatoid and psoriatic arthritis (15).
Fat – or adipose tissue – is involved in many physiological functions, including metabolism and immune system response. When adipose tissue accumulates and becomes dysfunctional, it can lead to increased or dysregulated secretion of compounds called adipokines (16). In this case, these bioactive substances tend to be pro-inflammatory and significantly alter immune system function.
In other words, obesity sends the body into a chronic state of low-grade inflammation and can threaten an otherwise healthy immune response.
Research in this area is ongoing, but we are discovering that these factors (and potentially others, like alteration of the gut microbiota and intestinal dysbiosis) can lead to organ damage, metabolic syndrome, and autoimmune conditions.
It is widely known that smoking cigarettes is not a healthy practice and can lead to cancer. Now, researchers are discovering that smoking is a risk factor in more than just respiratory conditions.
Smoking has been linked to rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and other autoimmune diseases (22).
Why? When you burn tobacco, thousands of chemicals are produced – some of which are known to be toxic. Inhaling that smoke impacts the immune system through various complex interactions, including inflammatory responses, immune suppression, dysregulation of cytokines (signaling molecules involved in autoimmunity), and the development of autoantibodies (23, 24, 25).
Exposure to other toxins like air pollutants, crystalline silica, ultraviolet radiation, or organic solvents are also associated with the development of autoimmune diseases like multiple sclerosis (26, 27, 28).
Moreover, a genetic predisposition to autoimmunity further increases your risk. Many toxic agents have the ability to alter gene expression. In a nutshell, they can activate an otherwise repressed gene or deactivate an active one, leading to disease.
Many people take pharmaceuticals on a daily basis to decrease blood pressure, manage depression and anxiety, or balance cholesterol levels. And it’s common knowledge that these drugs have potential side effects.
We’re discovering that in some cases, these side effects involve immune system function, and will trigger autoimmune reactions.
Early exposure to certain infections increases your susceptibility to autoimmune disease.
The presence of Epstein Barr Virus (EBV), which tends to present as a mild illness in childhood and then turn dormant, is associated with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjrogren’s syndrome (33, 34).
Another infectious microorganism – a bacteria called Group A Streptococcus – can trigger heart, joint, and brain-related autoimmune disease including acute rheumatic fever and rheumatic heart disease (35, 36).
These viruses interact with your genetics through a variety of mechanisms. In short, they can turn on certain genes that impact the immune system’s ability to differentiate between self and non-self, triggering an autoimmune reaction.
In some cases, such as being born female, your inherent level of risk cannot be controlled.
On the upside, there are a number of ways to avoid the accumulation of multiple risk factors and help prevent the onset of chronic illness, including:
As always, be sure to consult your doctor for information regarding your health.
Fairweather, D., Frisancho-Kiss, S., Rose, N. (2008). Sex Differences in Autoimmune Disease from a Pathological Perspective. The American Journal of Pathology, 173(3), 600-609.
Ørstavik, K. H. Why are autoimmune diseases more prevalent in women?
Ngo, S.T., Steyn F. J., McCombe P. A. (2014). Gender Differences in Autoimmune Disease. Frontiers in Neuroendocrinology, 35(3), 347-369.
Systemic Lupus Erythematosus. (2019). Genetics Home Reference, U.S. National Library Of Medicine.
Multiple Sclerosis. (2019). Genetics Home Reference, U.S. National Library Of Medicine.
Gene Mutation Study Sheds Light on Autoimmune Disease Development. (2014). Genetic Engineering and Biotechnology News.
Epigenetics. (n.d.). Genetics Science Learning Center, University of Utah.
Vojdani, A., Pollard M. K., Campbell A. W. (2014). Environmental Triggers and Autoimmunity. Autoimmune Diseases. doi: 10.1155/2014/798029
Weinhold, B. (2006). Epigenetics: The Science of Change. Environmental Health Perspectives, 114(3), A160-A167. doi: 10.1289/ehp.114-a160.
Ennis, C. (2014). Epigenetics 101: A Beginner’s Guide to Explaining Everything. The Guardian.
Epigenomics Fact Sheet. (2016). National Human Genome Research Institute.
Cojocar M., Cojocaru I. M., Silosi I. (2010). Multiple Autoimmune Syndrome. Maedica, Journal of Clinical Medicine. 5(2), 132-134.
Obesity Plays Major Role in Triggering Autoimmune Diseases. (2014). Tel Aviv University American Friends.
Obesity and Overweight. (2016). National Center for Health Statistics, Centers for Disease Control and Prevention.
Daïen C. I., Sellam J. (2015). Obesity and inflammatory arthritis: impact on occurrence, disease characteristics and therapeutic response RMD Open. doi: 10.1136/rmdopen-2014-000012
Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011). Adipokines in inflammation and metabolic disease. Nature reviews. Immunology, 11(2): 85–97. doi:10.1038/nri2921
Pragh G., Seres I., Harangi M., Fülöp P. (2014) Dynamic interplay between metabolic syndrome and immunity. Advances in Experimental Medicine and Biology, 824: 171-90. doi: 10.1007/978-3-319-07320-0_13
Versini M. Jeandel PY, Rosenthal E., Shoenfeld Y. (2014). Obesity in autoimmune diseases: not a passive bystander. Autoimmunity Reviews, 9: 981-1000. doi: 10.1016/j.autrev.2014.07.001.
Gremese E., Tolusso B., Gigante M. R., & Ferraccioli G. (2014). Obesity as a Risk and Severity Factor in Rheumatic Diseases (Autoimmune Chronic Inflammatory Diseases). Frontiers in immunology, 5, 576. doi:10.3389/fimmu.2014.00576.
Wensveen F. M., Valentić S., Šestan M., Wensveen TT., Polić B. (2015). Interactions between adipose tissue and the immune system in health and malnutrition. Seminars in Immunology, 5: 322-33. doi: 10.1016/j.smim.2015.10.006.
Lago F., Dieguez C., Gómez-Reino J., Gualillo O. (2007). Adipokines as emerging mediators of immune response and inflammation. Nature Clinical Practice Rheumatology 3(12).
Costenbader K. H., Karlson E. W. (2006). Cigarette smoking and autoimmune disease: what can we learn from epidemiology? Lupus, 15(11): 737-45.
Harel-Meir M., Sherer Y., Shoenfeld Y. (2007). Tobacco smoking and autoimmune rheumatic diseases. Nature Clinical Practice Rheumatology, 3: 707-715.
Arnson Y., Shoenfeld Y., Amital H. (2010). Effects of tobacco smoke on immunity, inflammation and autoimmunity. Journal of Autoimmunity, 34(3): J258-65. doi: 10.1016/j.jaut.2009.12.003
Perricone C., Versini M., Ben-Ami D., Gertel S., Watad A;, Segel M. J., Ceccarelli F., Conti F., Cantarini L., Bogdanos D. P., Antonelli A., Amital H., Valesini G., Shoenfeld Y. (2019). Smoke and Autoimmunity: The Fire Behind the Disease. In Mosaic of Autoimmunity, Chapter 37: 383-415. Academic Press.
Zhao C., Xu Z., Wu G., Mao Y., Liu L., QIan-Wu, Dan y., Tao S., Zhang Q., Sam N. B., Fan Y., Zou Y., Ye D., Pan H. (2019). Emerging role of air pollution in autoimmune diseases. Autoimmunity Reviews, 18(6): 607-614. Elsevier.
Miller F. W., Alfredsson L., Costenbader K. H., Kamen D. L., Nelson L. M., Norris J. M., De Roos A. J. (2012). Epidemiology of environmental exposures and human autoimmune diseases. Journal of Autoimmunity, 39(4): 259-71. doi: 10.1016/j.jaut.2012.05.002.
Barragán-Martínez, C., Speck-Hernández, C. A., Montoya-Ortiz, G., Mantilla, R. D., Anaya, J. M., & Rojas-Villarraga, A. Organic Solvents as Risk Factor for Autoimmune Diseases: A Systematic Review and Meta-Analysis. PLoS One, 7(12): e51506. doi:10.1371/journal.pone.
Charlesworth J. C., Curran J. E., Johnson M. P., Göring H. H., Dyer T. D., Diego V. P., Blangero J. (2010). Transcriptomic epidemiology of smoking: the effect of smoking on gene expression in lymphocytes. BMC medical genomics, 3, 29. doi:10.1186/1755-8794-3-29.
Lee K. W. & Pausova Z. (2013). Cigarette smoking and DNA methylation. Frontiers in genetics, 4, 132. doi:10.3389/fgene.2013.00132
What Are Common Symptoms of Autoimmune Disease? Johns Hopkins Medicine.
Castiella A., Zapata E., Lucena I. M., Andrade R. J. (2014) Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease. World Journal of Hepatology, 6(4), 160–168. doi:10.4254/wjh.v6.i4.160
Epstein-Barr virus and autoimmune diseases (2014). National Institutes of Health, Research Matters.
Draborg, A. H., Duus, K., & Houen, G. (2013). Epstein-Barr Virus in Systemic Autoimmune Diseases. Clinical & developmental immunology, 535738. doi:10.1155/2013/535738
Dale R. C. (2005). Post-streptococcal autoimmune disorders of the central nervous system. Developmental Medicine and Child Neurology, 47(11): 785-91.
Walker M. J., Barnett T. C., McArthur J. D., Cole J. N., Gillen C. M., Henningham A., Sriprakash K. S., Sanderson-Smith M. L., Nizet V. (2014). Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus. Clinical microbiology reviews, 27(2), 264–301. doi:10.1128/CMR.00101-13.
Harley J. B., Chen X., Pujato M., Miller D., Maddox A., Forney C., Magnusen A. F., Lynch A., Chetal K., Yukawa M., Barski A., Salomonis N., Kaufman K. M., Kottyan L. C., Weirauch M.T. (2018). Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Nature Genetics. 50: 699-707. doi: 10.1038/s41588-018-0102-3. [Epub ahead of print]. PMID: 29662164.
Getts, D. R., Chastain, E. M., Terry, R. L., & Miller, S. D. (2013). Virus infection, antiviral immunity, and autoimmunity. Immunological reviews, 255(1): 197–209. doi:10.1111/imr.12091.
Cusick M. F., Libbey J. E., & Fujinami R. S. (2012). Molecular mimicry as a mechanism of autoimmune disease. Clinical reviews in allergy & immunology, 42(1), 102–111. doi:10.1007/s12016-011-8294-7.
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