About Autoimmune Disease:

7 Risk Factors for Autoimmune Disease

Margaux Thieme-Burdette June 10, 2019

While researchers are still digging for answers on exactly what causes autoimmunity, 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.

Risk Factors

1. Sex 

In general, autoimmune disease affects females more than males. For instance, up to 95% of systemic lupus erythematosis (SLE) and Sjrogren’s syndrome patients are women (1). Other conditions like arthritis and multiple sclerosis occur in females around 60% more than in males (1).

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.

2. Genetics

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.

3. Having an autoimmune 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.

4. Obesity

Given that roughly 35% of the global population (12) and 72% of adults in the U.S. are overweight or obese (13), 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 (12). It has been found to increase the risk of developing autoimmune conditions like rheumatoid and psoriatic arthritis (14).

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 (15). 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.

5. Smoking and Exposure to Toxic Agents 

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 (21).

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 (22, 23, 24).

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 (25, 26, 27).

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.

6. Certain Medications

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.

Certain blood pressure medications, statins, and antibiotics can trigger drug-induced autoimmune conditions like lupus, myopathy, or autoimmune hepatitis (30, 31). 

7. Infections

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 (32, 33).

Another virus, called Group A Streptococcus, can trigger heart, joint, and brain-related autoimmune disease including acute rheumatic fever and rheumatic heart disease (34, 35).

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.

Decrease Your Risk

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:

  • Eating a nutritious diet and limiting processed foods
  • Incorporating physical movement into your daily life
  • Staying up-to-date on the latest information about your medications
  • Avoiding cigarettes

As always, be sure to consult your doctor for information regarding your health.

Sources

  1. Article Sources and Footnotes
    1. Ørstavik, K. H. Why are autoimmune diseases more prevalent in women?

    2. Ngo, S.T., Steyn F. J., McCombe P. A. (2014). Gender Differences in Autoimmune Disease. Frontiers in Neuroendocrinology, 35(3), 347-369.

       

    3. Systemic Lupus Erythematosus. (2019). Genetics Home Reference, U.S. National Library Of Medicine.

    4. Multiple Sclerosis. (2019). Genetics Home Reference, U.S. National Library Of Medicine.

    5. Gene Mutation Study Sheds Light on Autoimmune Disease Development. (2014). Genetic Engineering and Biotechnology News.

    6. Epigenetics. (n.d.). Genetics Science Learning Center, University of Utah.

    7. Vojdani, A., Pollard M. K., Campbell A. W. (2014). Environmental Triggers and AutoimmunityAutoimmune Diseases. doi: 10.1155/2014/798029

    8. Weinhold, B. (2006). Epigenetics: The Science of ChangeEnvironmental Health Perspectives, 114(3), A160-A167. doi: 10.1289/ehp.114-a160.

    9. Ennis, C. (2014). Epigenetics 101: A Beginner’s Guide to Explaining EverythingThe Guardian.

    10. Epigenomics Fact Sheet. (2016). National Human Genome Research Institute.

    11. Cojocar M., Cojocaru I. M., Silosi I. (2010). Multiple Autoimmune SyndromeMaedica, Journal of Clinical Medicine. 5(2), 132-134.

    12. Obesity Plays Major Role in Triggering Autoimmune Diseases. (2014). Tel Aviv University American Friends.

    13. Obesity and Overweight. (2016). National Center for Health Statistics, Centers for Disease Control and Prevention.

    14. 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

    15. 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 

    16. Pragh G., Seres I., Harangi M., Fülöp P. (2014) Dynamic interplay between metabolic syndrome and immunityAdvances in Experimental Medicine and Biology, 824: 171-90. doi: 10.1007/978-3-319-07320-0_13

    17. Versini M. Jeandel PY, Rosenthal E., Shoenfeld Y. (2014). Obesity in autoimmune diseases: not a passive bystanderAutoimmunity Reviews, 9: 981-1000. doi: 10.1016/j.autrev.2014.07.001.

    18. 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. 

    19. Wensveen F. M., Valentić S., Šestan M., Wensveen TT., Polić B. (2015). Interactions between adipose tissue and the immune system in health and malnutritionSeminars in Immunology, 5: 322-33. doi: 10.1016/j.smim.2015.10.006.

    20. Lago F., Dieguez C., Gómez-Reino J., Gualillo O. (2007). Adipokines as emerging mediators of immune response and inflammationNature Clinical Practice Rheumatology 3(12).

    21. Costenbader K. H., Karlson E. W. (2006). Cigarette smoking and autoimmune disease: what can we learn from epidemiology? Lupus, 15(11): 737-45.

    22. Harel-Meir M., Sherer Y., Shoenfeld Y. (2007). Tobacco smoking and autoimmune rheumatic diseasesNature Clinical Practice Rheumatology, 3: 707-715.

    23. 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

    24. 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.

    25. 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 diseasesAutoimmunity Reviews, 18(6): 607-614. Elsevier.

    26. 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 diseasesJournal of Autoimmunity, 39(4): 259-71. doi: 10.1016/j.jaut.2012.05.002.

    27. Barragán-Martínez, C., Speck-Hernández, C. A., Montoya-Ortiz, G., Mantilla, R. D., Anaya, J. M., & Rojas-Villarraga, AOrganic Solvents as Risk Factor for Autoimmune Diseases: A Systematic Review and Meta-AnalysisPLoS One, 7(12): e51506. doi:10.1371/journal.pone.0051506.

    28. 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 lymphocytesBMC medical genomics3, 29. doi:10.1186/1755-8794-3-29.

    29. Lee K. W. & Pausova Z. (2013). Cigarette smoking and DNA methylation. Frontiers in genetics, 4, 132. doi:10.3389/fgene.2013.00132

    30. What Are Common Symptoms of Autoimmune Disease? Johns Hopkins Medicine.

    31. Castiella A., Zapata E., Lucena I. M., Andrade R. J. (2014) Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported diseaseWorld Journal of Hepatology, 6(4), 160–168. doi:10.4254/wjh.v6.i4.160

    32. Epstein-Barr virus and autoimmune diseases (2014). National Institutes of Health, Research Matters.

    33. Draborg, A. H., Duus, K., & Houen, G. (2013). Epstein-Barr Virus in Systemic Autoimmune DiseasesClinical & developmental immunology, 535738. doi:10.1155/2013/535738

    34. Dale R. C. (2005). Post-streptococcal autoimmune disorders of the central nervous system. Developmental Medicine and Child Neurology, 47(11): 785-91.

    35. 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 reviews27(2), 264–301. doi:10.1128/CMR.00101-13.

    36. 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.

    37. 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.

    38. Cusick M. F., Libbey J. E., & Fujinami R. S. (2012). Molecular mimicry as a mechanism of autoimmune diseaseClinical reviews in allergy & immunology, 42(1), 102–111. doi:10.1007/s12016-011-8294-7.