Autoimmune diseases are diseases where the body’s immune system mistakenly attacks itself, i.e., the body’s own tissues and organs depending on the type. More than 80 of them have been identified to date and they can vary a lot in severity and symptoms and which body part is targeted. Very well known ones are type 1 diabetes, psoriasis, hashimoto’s disease (hypothyroidism), IBD (see essay on it here), multiple sclerosis. Just by listing a few you can see the variety of organs it can affect; pancreas, skin, thyroid, gut, central nervous system (brain & spinal cord), respectively.
History & Cause
As a concept it was first recognised in the early 20th century, that being said until the 1950s they thought the immune system could only attack foreign substances. Then they realised that it could also attack the body’s own cells mistakenly. They were first identified by Paul Ehrlich, and he named it horror autotoxicus. In more biological terms what happens in autoimmunity, is that the lymphocytes (a type of white blood cell) undergoes abnormal reactions against the body’s own proteins. This is due problems in the development or regulation of B or T lymphocytes - these play a major role in the immune system1. You’ve probably also heard of immunotherapy to treat cancer and other diseases, it is either B or T cell involving.
The cause has not exactly been found or understood, but we know that genetics, environmental, and immunological factors can trigger it. These are not the only ones, below I expand a bit on what it is that may trigger the creation of it.
The genetic part is quite self explanatory, just puts on at an increased rate but it does not guarantee that it will happen.
Environmental includes viral / bacterial infections that may trigger it, chemical and toxin exposure (like other diseases, e.g., cancer) and of course lifestyle and diet, e.g. obesity.
Hormonal influences, sex hormones like oestrogen are speculated to play a role and hence the higher prevalence in women
Gut microbiome, there’s a clear connection between the gut - brain axis, and changes within the gut are thought to affect the immune regulation, probably also due to the inflammation occurring in the gut. This is also why a lot of such diseases suggest dietary changes for the control and management of symptoms.
Stress & psychological factors, no surprise here, like many many diseases it can trigger the onset or make the symptoms even worse
Diagnosis
Diagnosis is not that straight forward, as symptoms and severity vary a lot, and in many cases are quite generic to begin with part of it is process of elimination - of course this is depending on the autoimmune disease. Blood tests are the first point of contact, with the antinuclear antibody test (ANA) being one of the first ones to do. A positive result would indicate the presence of autoantibodies. Erythrocyte sedimentation rate (ESR) and C-Reactive Protein (CRP) are also used to measure inflammation levels. If a specific autoimmune disease is speculated, there are specific antibody tests as well, like anti-TPo for autoimmune thyroid disease.
Tests may continue and include imaging, like MRI and CT scans to assess level of inflammation and even biopsies of certain tissues to confirm a diagnosis, e.g., GI for IBD.
Another difficulty is that the symptoms may appear in many autoimmune diseases so it’s a bit challenging to know from the get-go which one it actually is. A very common symptom is fatigue and tummy pain, which basically is a symptom of hundreds of things.
Prevalence & Incidence
The incidence of autoimmune disease is on the rise worldwide, with around 1 in 10 people being affected by it. A 2023 study published in Lancet, looked at 22M people in the UK from Jan-2000 to June-20192. 4.5% of the pop had new diagnosis of at least one autoimmune disease; of those, 63.9% were women and 36.1% men. They also compared the incidence rates in 2000-02 with 2017-19, and they saw increases for the following: coeliac disease (IRR=2.19), Sjogren’s syndrome (IRR=2.09), and Grave’s disease (IRR=2.07) but pernicious anaemia (IRR=0.79), and Hashimoto’s thyroiditis (IRR=0.81) saw a decrease. Overall, 10.2% of the pop across the whole study period had at least 1 of the 19 autoimmune disorders examined, with women almost being twice as many as the men.
It’s clear that around twice as many women are affected by autoimmune disease, outside of the female sexual hormones which we touched upon above, there are a few more reasons that may affect it. The genetic factor is quite important, most autoimmune disease are linked to genes on the X chromosome and as women have two of them, in comparison to men having XY chromosomes, and in combination with the X-chromosome inactivation which is not always complete in women leads to a potentially increased expression in such genes3. Another aspect of the hormonal changes also coincides with the diagnosis and triggering of autoimmune diseases, these two events are puberty and pregnancy where the largest change in sexual hormones occurs.
A new virus that was linked with autoimmune disease was that of COVID-19 post infection, to no surprise. There are multiple case reports and small series around it, but also two large cohort studies that link infection with a substantially increased risk in the development and onset of new autoimmune diseases4. As summarised by Eric Topol, it’s clear that the increased risk is very high, especially in the German study.
The German and UK study are not yet peer-reviewed, so won’t focus on them as much. The US one provided the crude and adjusted hazard ratios for each disease looked at, at an overall cohort level, sex, age, and race. They also looked at the severity of COVID-19 (inpatient vs outpatient), and region (EMEA vs global). Even when it comes to those getting covid, the incidence in women is still higher in both the crude and adjusted models. However, mortality due to covid was higher in men.
The last thing I’ll touch on is that of microplastics and endocrine disruptors. Although the full mechanisms of microplastics are unclear when it comes to the immunotoxicity effects, which will of course be dependent on the composition of the item, shape, size, and combined exposure - it’s vital that the immunological hazard and thus risk of humans is studied, as well as the exposure amount5. A recent study did show that they had vastly underestimated the amount of microplastic present in bottled water6 . Now, both microplastics and nanoplastics contain endocrine disrupting compounds which have been proven that they can impact different endocrine components of mammals like the thyroid, ovaries, pituitary gland and more7. As these are associate with the body’s hormonal system including the sexual hormones it’s possible that the consumption of them may also play a part in the triggering of autoimmune diseases. Such particles have been found in water and salt, as well as within the food we consume8. A 2023 review of endocrine disrupting chemicals (EDCs) and autoimmune disease, showed the impact of various EDCs on the various diseases as well as the potential mechanism in which the EDCs affect these diseases9 . They concluded that exposure to EDCs accelerated the onset and progression of autoimmune disease, but quite interestingly they did note that some EDCs appeared to have an immunosuppressive effect with slowing down the progression of autoimmune disease. Of course, it is hard to know the true exposure of to EDCs as well as the amount of it.
Burden of disease
A big indication of the increased incidence and burden of diseases, is the spending of capital on autoimmune disease. In 2011, US$23B was spent, this was more than quintupled in 10 years, with $US127B being spent in 202110. Studies have classified as autoimmune diseases among the most costly diseases to both diagnose and treat, due to them being chronic diseases which are lifetime, with no cure11. Although they are chronic they do not affect lifespan, meaning they are affecting quality of life but not shortening it - from a healthcare perspective this equates to a higher lifetime cost of healthcare in comparison to an average person that does not have such a disease.
To summarise, autoimmune diseases are becoming more and more prevalent even in high income countries. Evidently lifestyle is a major factor, outside of gender of course. Although there are no direct cures at the moment, there is more awareness and research being done on them. As these tend to be lifetime diseases, the burden of disease is quite high, impacting both the individual as well as the healthcare sector. A UK based start up, named Kuma Health, is working on transforming the care of those with autoimmune disease via personalised medicine. This is another example of how important it is to take care of your body and pay attention as to what you consume. Of course having a genetic predisposition makes you more likely to get it, but that does not mean that it will indeed happen.
As usual, I’ve added some links below. I hope you enjoyed - see you next week! :)
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