Are you living with Celiac disease? Chances are you regularly deal with people who make light of your diagnosis and do not believe how that slice of non-gluten-free pizza can trigger severe symptoms [1]. How about multiple sclerosis (MS)? People diagnosed with MS report facing social exclusion, which further compounds the difficulties of living with the condition [2].
The gap is that staggering in the understanding of autoimmune diseases. That doesn’t stem only from the public, but it can be seen within healthcare as well. Many patients with autoimmune symptoms are told that “nothing’s wrong” or “it’s probably stress.”
Unfortunately, the reality is that autoimmune diseases are on the rise worldwide. So today on the Rejuve.AI blog, we will talk all about these conditions, explore why they are increasing, and discuss whether you can take steps to prevent them.
What Are Autoimmune Diseases?
Your immune system is one remarkably mighty army. It protects you from infections, malignancies, and injuries, among other threats. With such a wide range of defensive tactics, one crucial ability it must have is recognizing the difference between self and non-self — distinguishing your own biology from any potential intruders.
When the immune system mistakenly targets a normal part of your body, autoimmune diseases can develop [3]. Discovery of autoimmunity goes back to the early 1900s when it was referred to in medical literature as “horror autotoxicus” [4].
Instead of targeting harmful invaders, your immune system turns against you. This is different from allergies, where the immune system mistakenly sees harmless substances, like pollen or food, as dangerous and reacts as it would when trying to fight a pathogen. Both autoimmune diseases and allergies involve the immune system being confused about what is safe and what isn’t [5].
Autoimmune diseases have a major impact on the individuals and families they affect, as well as on society and healthcare costs. In the U.S. alone, direct medical costs exceed $100 billion annually — a figure that doesn’t account for lost productivity, reduced incomes, or the toll on caregivers [6]. The true cost of these conditions reaches far deeper than current statistics show.
Types of Autoimmune Diseases
There are now more than 140 recognized autoimmune diseases [7], generally classified as either organ-specific or systemic. In organ-specific disorders, the immune system primarily targets an individual organ. In systemic disorders, autoimmune activity affects multiple areas of the body.
Examples of Organ-Specific Autoimmune Disorders:
Celiac Disease
Inflammatory Bowel Disease
Type 1 Diabetes
Multiple Sclerosis
Hashimoto’s Thyroiditis
Examples of Systemic Autoimmune Disorders:
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Sjögren’s Syndrome
Fibromyalgia
Scleroderma
Prevalence of Autoimmune Diseases
Today, it’s estimated that 5% of the global population is living with an autoimmune disease [8]. While this is a significant number, the real concern lies in the rapid increase of cases.
In the U.S., this trend has been well-documented through studies tracking autoantibodies — antibodies that mistakenly attack the body’s own tissues. One of the most clinically relevant types is antinuclear antibodies (ANA). Data from the National Health and Nutrition Examination Survey (NHANES) showed that ANA prevalence nearly doubled, rising from 22.3 million people in 1988 to 41.5 million in 2012 [9].
Although aging increases the risk of autoimmunity [10], the most striking rise occurred in teenagers. Between 1988 and 2012, ANA levels in teenagers surged by nearly 300%. These chronic illnesses can substantially alter the lives of these teenagers and hinder them from achieving their full potential.
Age isn’t the only factor at play. Sex also plays a major role, with women accounting for nearly 80% of those diagnosed with autoimmune diseases [11]. Race also influences risk. Some autoimmune diseases are more severe in Black, Hispanic, and Indigenous populations, while others are more common among White individuals [12, 13].
Genetic factors may help explain these disparities. Many genes that increase susceptibility to autoimmune diseases regulate immune responses, such as the gene for the Human leukocyte antigen (HLA). HLA helps the immune system distinguish between self and non-self cells [14].
However, genetics alone don’t tell the full story behind the surge in autoimmune diseases.
Environmental Triggers: The Reason Autoimmune Diseases Are on the Rise?
As Dr. James Lee of the Francis Crick Institute says:
“Human genetics hasn’t altered over the past few decades, so something must be changing in the outside world in a way that is increasing our predisposition to autoimmune disease.”
Indeed, mounting evidence supports the idea that environmental factors are driving the rise of autoimmune diseases. Studies show that identical twins, despite sharing the same DNA, do not always develop the same autoimmune diseases if they develop any at all [15]. There are also well-documented cases of symptoms improving when a person stops exposure to certain environmental agents — called “dechallenging” — and returning when exposure resumes, known as “rechallenging” [16, 17].
Findings like these support what scientists call the “second-hit hypothesis” of autoimmune disease [18]. It states that our genes are neither inherently good nor bad, but our environments make them so. This means that a person may carry genetic risk for an autoimmune disease their entire life but only develop the condition when exposed to a second, environmental trigger.
Since many autoimmune diseases share genetic risk factors, the specific environmental exposure may also determine which disease a person develops [18]. While this gene-environment relationship is highly complex and requires further research, several environmental triggers have been identified as contributors to autoimmune disease risk, including:
Infections
Certain bacterial and viral infections have been linked to autoimmune disease development. For example, research suggests that Epstein-Barr virus (EBV) infection or reactivation often precedes some autoimmune disorders, such as multiple sclerosis [19].
One of the strongest examples of a virus triggering autoimmunity comes from SARS-CoV-2, the virus that causes COVID-19. Studies show that myocarditis, an autoimmune condition affecting the heart, develops in approximately 4.5% of COVID-19 cases [20].
Western Diet
A diet high in fat, cholesterol, sugar, and salt — often referred to as a “Western diet” — has been associated with obesity and metabolic disorders, both of which increase inflammation in the body. Excess fat tissue secretes molecules called adipokines, which keep the immune system in a prolonged state of low-grade inflammation. Over time, this can contribute to the development of autoimmune disease [21].
Western diets also tend to lack fiber, which can lead to an imbalance in the gut microbiome, also known as dysbiosis. This dysbiosis is the primary driver of gut-related autoimmune diseases like inflammatory bowel disease [22].
Xenobiotics
Xenobiotics are foreign substances that do not naturally occur in the body or environment, including industrial chemicals, pesticides, pollutants, and certain drugs. Their link to autoimmune disease has been recognized for decades [23].
One of the most well-known cases was the 1981 Spanish Toxic Oil Syndrome epidemic, in which thousands of people developed illnesses after consuming industrially denatured rapeseed oil sold fraudulently as olive oil. Approximately 15% of affected individuals exhibited symptoms of autoimmune diseases such as Sjögren’s syndrome and scleroderma [24].
Stress
Up to 80% of patients report experiencing significant emotional stress before the onset of an autoimmune disease. Stress is not only a potential trigger for disease but also an ongoing burden for those living with chronic illness, creating a vicious cycle.
The biological link between stress and autoimmunity lies in the hormonal response. Stress hormones can alter immune function and drive inflammation by increasing the production of cytokines — molecules that regulate immune responses and, when overproduced, contribute to autoimmune disease [25].
Smoking
Cigarette smoking has long been recognized as a risk factor for chronic diseases, including autoimmune disorders. Population studies suggest a dose-dependent relationship: the more someone smokes, the greater their risk of developing an autoimmune disease [18].
The mechanisms behind this association include increased oxidative stress, damage to immune-regulating cells, and disruption of normal immune responses [26].
Air Pollutants
Environmental shifts caused by climate change are increasingly recognized as contributors to autoimmune disease. Airborne pollutants, in particular, have been shown to trigger immune responses that may promote autoimmunity [27].
In fact, a population study in Italy investigated the relationship between the incidence of autoimmune diseases and the concentration of particulate matter less than 10 microns in diameter (PM10) in the air. It found that for every 10 micrograms per cubic meter increase in PM10, there is a 7% higher risk of developing an autoimmune disease [28].
Diagnosis of Autoimmune Diseases
For many, the most exhausting part of their autoimmune journey is getting their diagnosis.
Diagnosis, which is only the start of the road to getting treatment, takes four years from the onset of symptoms on average [29]. This reflects on the broader issue we discussed earlier: autoimmune diseases are still not well understood by healthcare professionals. At the root of this problem is a lack of research and consensus, including disagreements over how to define autoimmune diseases in the first place [30].
Nonetheless, blood tests can help assess autoimmune activity, including erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and the aforementioned anti-nuclear antibodies [31]. However, these tests lack predictive value and may be elevated in other conditions.
Because of this, symptoms remain the primary basis for diagnosis. Common symptoms include joint and muscle aches, fatigue, brain fog, digestive issues, swollen glands, and recurring fevers [32]. Unfortunately, these are also symptoms of many other conditions, making autoimmune diseases difficult to pinpoint.
With non-specific lab tests and overlapping symptoms, diagnosing an autoimmune disorder often feels like detective work. Specialty clinics focused on autoimmunity can be valuable, as they offer physicians who understand the complexity of these diseases and are willing to work with patients to find answers.
What If You’re Pre-Autoimmune?
Remember the NHANES data we referenced in the beginning? Well, it shows a very interesting insight. 15% of individuals involved were positive for antinuclear antibodies — including children — without actually showing any autoimmune symptoms [9].
Thankfully, not everyone in this group ends up developing autoimmune diseases. But for the others, they are in a state of pre-clinical autoimmunity. Scientists define that as a period of time in which autoimmunity is present — as assessed by the presence of autoantibodies — in the absence of classic symptoms of disease [33].
In these pre-autoimmune individuals, immune dysfunction may have already started but it can take up to ten years for clinical signs to develop [34]. Yes, that’s potentially a decade of symptom-free living in pre-autoimmunity, which is a golden opportunity for affected people to course-correct.
That means optimizing lifestyle and avoiding as much as possible the environmental triggers of autoimmune disease. Some triggers will be easier to avert such as Western diets while air pollution is certainly more challenging. But ultimately, the reward should be worth it because research shows autoantibody levels can revert with the risk of developing autoimmune diseases decreasing [35].
Clinical trials with pre-autoimmune participants are also underway to test whether different interventions can prevent autoimmune diseases. Some of the interventions being tested include Vitamin D and omega-3 supplements, which collectively showed a diminished risk of autoimmune diseases in a trial involving older adults [36].
Conclusion
There’s reason for optimism in the fight against autoimmune diseases. Prevention trials and emerging therapies are laying the groundwork for better outcomes. However, as Dr. Frederick Miller, former head of the NIH’s Environmental Autoimmunity Group, puts it:
“The evolving autoimmune epidemic will continue to have increasingly devastating impacts on those affected, their families, and our society unless we focus much more attention and research into the causes, better diagnostics, and improved treatments and prevention.”
One of the most pressing needs is the discovery of more robust biomarkers that can identify at-risk individuals before disease onset. This would pave the way for standardized screening protocols and earlier interventions. However, for that to happen, large-scale data needs to be collected — especially from those already experiencing early warning signs but struggling to find answers.
Decentralizing autoimmune research could be a game-changer. At Rejuve.AI, we’re building the world’s first decentralized platform dedicated to aging research — empowering people to contribute their health data while accelerating discoveries through AI-driven insights.
A similar approach for autoimmune diseases could provide researchers with the diverse, real-world data needed to bridge the gaps in diagnosis and prevention.
Perhaps one day, instead of hearing “Nothing’s wrong with you,” those seeking answers will finally be met with, “Here’s what we can do to help — before it even starts.”
References:
[1] Rose-Marie Satherley, Lerigo, F., & Pitt, A. (2023). Experiences of Health-Related Stigma and Challenges Faced by Men Living with Celiac Disease: A Qualitative Analysis. Journal of the Academy of Nutrition and Dietetics. https://doi.org/10.1016/j.jand.2023.11.018
[2] Anagnostouli, M., Katsavos, S., Artemiadis, A., Zacharis, M., Argyrou, P., Theotoka, I., Christidi, F., Zalonis, I., & Liappas, I. (2016). Determinants of stigma in a cohort of hellenic patients suffering from multiple sclerosis: a cross-sectional study. BMC Neurology, 16(1). https://doi.org/10.1186/s12883-016-0621-4
[3] Pisetsky, D. S. (2023). Pathogenesis of Autoimmune Disease. Nature Reviews Nephrology, 19(8), 1–16. https://doi.org/10.1038/s41581-023-00720-1
[4] Ahsan, H. (2022). Origins and history of autoimmunity — A brief review. Rheumatology & Autoimmunity. https://doi.org/10.1002/rai2.12049
[5] Krishna, M. T., Subramanian, A., Adderley, N. J., Zemedikun, D. T., Gkoutos, G. V., & Nirantharakumar, K. (2019). Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis. European Respiratory Journal, 54(5), 1900476. https://doi.org/10.1183/13993003.00476-2019
[6] Rosenblum, M. D., Gratz, I. K., Paw, J. S., & Abbas, A. K. (2012). Treating Human Autoimmunity: Current Practice and Future Prospects. Science Translational Medicine, 4(125), 125sr1–125sr1. https://doi.org/10.1126/scitranslmed.3003504
[7] About the Office of Autoimmune Disease Research (OADR-ORWH). (n.d.). Orwh.od.nih.gov. Retrieved May 8, 2024, from https://orwh.od.nih.gov/OADR-ORWH
[8] Cooper, G. S., Bynum, M. L. K., & Somers, E. C. (2009). Recent insights in the epidemiology of autoimmune diseases: Improved prevalence estimates and understanding of clustering of diseases. Journal of Autoimmunity, 33(3–4), 197–207. https://doi.org/10.1016/j.jaut.2009.09.008
[9] Dinse, G. E., Parks, C. G., Weinberg, C. R., Co, C. A., Wilkerson, J., Zeldin, D. C., Chan, E. K. L., & Miller, F. W. (2022). Increasing Prevalence of Antinuclear Antibodies in the United States. Arthritis & Rheumatology. https://doi.org/10.1002/art.42330
[10] Goronzy, J. J., & Weyand, C. M. (2012). Immune aging and autoimmunity. Cellular and Molecular Life Sciences: CMLS, 69(10), 1615–1623. https://doi.org/10.1007/s00018-012-0970-0
[11] Fairweather, D., Frisancho-Kiss, S., & Rose, N. R. (2008). Sex Differences in Autoimmune Disease from a Pathological Perspective. The American Journal of Pathology, 173(3), 600–609. https://doi.org/10.2353/ajpath.2008.071008
[12] Izmirly, P. M., Parton, H., Wang, L., McCune, W. J., Lim, S. S., Drenkard, C., Ferucci, E. D., Dall’Era, M., Gordon, C., Helmick, C. G., & Somers, E. C. (2021). Prevalence of Systemic Lupus Erythematosus in the United States: Estimates From a Meta‐Analysis of the Centers for Disease Control and Prevention National Lupus Registries. Arthritis & Rheumatology, 73(6). https://doi.org/10.1002/art.41632
[13] Dabelea, D., Mayer-Davis, E. J., Saydah, S., Imperatore, G., Linder, B., Divers, J., Bell, R., Badaru, A., Talton, J. W., Crume, T., Liese, A. D., Merchant, A. T., Lawrence, J. M., Reynolds, K., Dolan, L., Liu, L. L., Hamman, R. F., & SEARCH for Diabetes in Youth Study. (2014). Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA, 311(17), 1778–1786. https://doi.org/10.1001/jama.2014.3201
[14] Matzaraki, V., Kumar, V., Wijmenga, C., & Zhernakova, A. (2017). The MHC locus and genetic susceptibility to autoimmune and infectious diseases. Genome Biology, 18(1). https://doi.org/10.1186/s13059-017-1207-1
[15] Bogdanos, D. P., Smyk, D. S., Rigopoulou, E. I., Mytilinaiou, M. G., Heneghan, M. A., Selmi, C., & Eric Gershwin, M. (2012). Twin studies in autoimmune disease: Genetics, gender and environment. Journal of Autoimmunity, 38(2), J156–J169. https://doi.org/10.1016/j.jaut.2011.11.003
[16] Miller, F. W., Pollard, K. M., Parks, C. G., Germolec, D. R., Leung, P. S. C., Selmi, C., Humble, M. C., & Rose, N. R. (2012). Criteria for environmentally associated autoimmune diseases. Journal of Autoimmunity, 39(4), 253–258. https://doi.org/10.1016/j.jaut.2012.05.001
[17] Arnaud, L., Mertz, P., Gavand, P.-E., Martin, T., Chasset, F., Tebacher-Alt, M., Lambert, A., Muller, C., Sibilia, J., Lebrun-Vignes, B., & Salem, J.-E. (2019). Drug-induced systemic lupus: revisiting the ever-changing spectrum of the disease using the WHO pharmacovigilance database. Annals of the Rheumatic Diseases, 78(4), 504–508. https://doi.org/10.1136/annrheumdis-2018-214598
[18] National Academies of Sciences, Engineering, and Medicine. 2022. Enhancing NIH Research on Autoimmune Disease. Washington, DC: The National Academies Press. https://doi.org/10.17226/26554.
[19] Bjornevik, K., Cortese, M., Healy, B. C., Kuhle, J., Mina, M. J., Leng, Y., Elledge, S. J., Niebuhr, D. W., Scher, A. I., Munger, K. L., & Ascherio, A. (2022). Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science, 375(6578). https://doi.org/10.1126/science.abj8222
[20] Kawakami, R., Sakamoto, A., Kawai, K., Gianatti, A., Pellegrini, D., Nasr, A., Kutys, B., Guo, L., Cornelissen, A., Mori, M., Sato, Y., Pescetelli, I., Brivio, M., Romero, M., Guagliumi, G., Virmani, R., & Finn, A. V. (2021). Pathological Evidence for SARS-CoV-2 as a Cause of Myocarditis. Journal of the American College of Cardiology, 77(3), 314–325. https://doi.org/10.1016/j.jacc.2020.11.031
[21] Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011). Adipokines in inflammation and metabolic disease. Nature Reviews Immunology, 11(2), 85–97. https://doi.org/10.1038/nri2921
[22] Mousa, W. K., Chehadeh, F., & Husband, S. (2022). Microbial dysbiosis in the gut drives systemic autoimmune diseases. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.906258
[23] Pollard, K. M., Christy, J. M., Cauvi, D. M., & Kono, D. H. (2017). Environmental xenobiotic exposure and autoimmunity. Current Opinion in Toxicology, 10, 15–22. https://doi.org/10.1016/j.cotox.2017.11.009
[24] Alonso-Ruiz, A., Zea-Mendoza, A. C., Salazar-Vallinas, JoséM., Rocamora-Ripoll, A., & Beltrán-Gutiérrez, J. (1986). Toxic oil syndrome: A syndrome with features overlapping those of various forms of scleroderma. Seminars in Arthritis and Rheumatism, 15(3), 200–212. https://doi.org/10.1016/0049-0172(86)90017-x
[25] Stojanovich, L., & Marisavljevich, D. (2008). Stress as a trigger of autoimmune disease. Autoimmunity Reviews, 7(3), 209–213. https://doi.org/10.1016/j.autrev.2007.11.007
[26] 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. (2016). Smoke and autoimmunity: The fire behind the disease. Autoimmunity Reviews, 15(4), 354–374. https://doi.org/10.1016/j.autrev.2016.01.001
[27] Ioana Agache, Cezmi Akdis, Mubeccel Akdis, Al-Hemoud, A., Annesi-Maesano, I., Balmes, J., Cecchi, L., Athanasios Damialis, Haahtela, T., Haber, A. L., Hart, J. E., Marek Jutel, Yasutaka Mitamura, Mmbaga, B. T., Oh, J.-W., Abbas Ostadtaghizadeh, Pawankar, R., Prunicki, M., Renz, H., & Rice, M. B. (2024). Immune-mediated disease caused by climate change-associated environmental hazards: mitigation and adaptation. Frontiers in Science (Lausanne), 2. https://doi.org/10.3389/fsci.2024.1279192
[28] Adami, G., Pontalti, M., Cattani, G., Rossini, M., Viapiana, O., Orsolini, G., Benini, C., Bertoldo, E., Fracassi, E., Gatti, D., & Fassio, A. (2022). Association between long-term exposure to air pollution and immune-mediated diseases: a population-based cohort study. RMD Open, 8(1), e002055. https://doi.org/10.1136/rmdopen-2021-002055
[29] Global Autoimmune Institute. (2024, April 29). Misdiagnosed & Undiagnosed: Expert Insights on the Autoimmune Diagnosis Process https://www.autoimmuneinstitute.org/articles/misdiagnosed-undiagnosed-expert-insights-on-the-autoimmune-diagnosis-process/
[30] Miller, F. W. (2023). The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention. Current Opinion in Immunology, 80(102266), 102266. https://doi.org/10.1016/j.coi.2022.102266
[31] Castro, C., & Gourley, M. (2010). Diagnostic testing and interpretation of tests for autoimmunity. Journal of Allergy and Clinical Immunology, 125(2), S238–S247. https://doi.org/10.1016/j.jaci.2009.09.041
[32] Pisetsky, D. S. (2023). Pathogenesis of Autoimmune Disease. Nature Reviews Nephrology, 19(8), 1–16. https://doi.org/10.1038/s41581-023-00720-1
[33] Olsen, N. J., Okuda, D. T., Holers, V. M., & Karp, D. R. (2022). Editorial: Understanding the concept of pre-clinical autoimmunity. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.983310
[34] Slight‐Webb, S., Bourn, R. L., V. Michael Holers, & James, J. A. (2019). Shared and unique immune alterations in pre-clinical autoimmunity. Current Opinion in Immunology, 61, 60–68. https://doi.org/10.1016/j.coi.2019.08.006
[35] So, M., O’Rourke, C., Bahnson, H. T., Greenbaum, C. J., & Speake, C. (2020). Autoantibody Reversion: Changing Risk Categories in Multiple-Autoantibody–Positive Individuals. Diabetes Care, 43(4), 913–917. https://doi.org/10.2337/dc19-1731
[36] Hahn, J., Cook, N. R., Alexander, E. K., Friedman, S., Walter, J., Bubes, V., Kotler, G., Lee, I.-M., Manson, J. E., & Costenbader, K. H. (2022). Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ, 376, e066452. https://doi.org/10.1136/bmj-2021-066452