Autoimmunity on the Rise

With autoimmune biomarkers (substances in the body that can be measured in order to help determine the intensity of a disease or other physiological state) increasing in prevalence, some researchers are looking at the association between autoimmunity and environmental factors like microplastics to explain this trend.

The best guess that current research literature has is that an estimated 4 percent of the world’s population has at least one autoimmune disease. In the United States, that number may be closer to 8 percent [1]—and those rates aren’t static. Experts say they’ve been increasing for decades [2,3,4]. 

A 2020 study in Arthritis Rheumatology found a steady rise over time in the frequency of antinuclear antibodies (ANA), proteins that occur in autoimmune diseases like lupus, scleroderma, and Sjögren’s [3]. These findings further suggest that autoimmune diseases are becoming more prevalent. Now, researchers are zeroing in on environmental factors in an effort to explain why.

What are antinuclear antibodies (ANA)?

In the human body, specialized white blood cells make antibodies that defend against pathogens. These are adaptable proteins with highly variable regions, meaning that once the immune system recognizes a specific bacteria or virus as foreign to the body, it can crank out custom antibodies that target those microorganisms. The antibodies neutralize the pathogen and recruit other proteins and cells to help fight the infection. This collective response is inflammation.

Usually, this system works like a charm—but for reasons that are still unclear, the immune system sometimes turns its pathogen-busting attention toward the body’s own proteins by making ANA.

These autoantibodies initiate an inflammatory response that damages the body’s own healthy cells and can lead to the development of an autoimmune disease.

Many people have some ANA circulating in their bloodstream and may never go on to develop an autoimmune disease. The immune system usually has regulatory mechanisms to keep autoantibodies in check [4]. Those mechanisms may not function correctly for people with autoimmune diseases. ANA remains the primary clinical indicator of immune dysfunction for people with autoimmune diseases—and can show up in blood tests years before diagnosis [4].

ANA on the Rise

To learn more about the increase in autoimmune disease over time, researchers turned to the US National Health and Nutrition Examination Survey, which has continuously collected information from questionnaires and physical exams since 1999 and releases data to the public every two years. [3]. 

The researchers used a method called immunofluorescence on preserved blood serum samples from 14,211 people stored over a 25-year time span. Samples were organized into three separate time periods and tested for ANA. The technique, which stains antibodies in the serum so they glow under a microscope, revealed a marked increase in ANA over time—especially in the most recent cohort (Figure 1) [3]. 

Figure 1: Results from Dinse study (2020).

The increase in autoimmune markers was steepest for adolescents aged 12 to 19 years; in fact, their ANA rate almost tripled by the end of the study [3]. The researchers also noted significant increases for men, adults over 50, and non-Hispanic white people. 

These broad findings correlate with previous work that shows an uptick in multiple sclerosis (MS), systemic lupus erythematosus (SLE), and diabetes, to name a few [5,6,7]. The researchers dug into the sociological data that accompanied each of those serum samples and reported that the increases in ANA could not be explained by trends in things like body size, smoking history, or alcohol use [3].

Why is ANA increasing?

So, what could be at the root of this increase in ANA and autoimmune conditions? While it’s true that autoimmune diseases have a genetic component, experts say genetics are insufficient to explain the rise in ANA and autoimmunity [4].  Over the years, environmental exposures—including pollutants, medications, dietary components, viral infections, and stress—have been linked to autoimmunity [4].

In fact, scientists say environmental factors may be responsible for up to 70 percent of autoimmune diseases [8]

Some of those associations involve obvious toxins like pesticides, mercury, solvents, and crystalline silicates. The latter—minerals found in stone, sand, and soil that become respirable dust during construction activities—have been associated with rheumatoid arthritis, SLE, autoimmune hepatitis, systemic sclerosis, and scleroderma for many years [2]. When these aerosolized compounds make their way into the lungs, immune cells mount an inflammatory response and may eventually cause the body to lose tolerance to its own cells and generate autoantibodies [2].

Environmental exposure can also dysregulate the microbiome. These beneficial bacteria live in the gut, helping digest food and supporting the immune system. When the balance of microbes in the gut community is thrown off—by inflammation, hormonal triggers, oxidative stress, or other mechanisms—the result is even more inflammation, autoimmunity, and the development of conditions like SLE, MS, RA, IBD, diabetes, and ulcerative colitis [8]. 

Emerging Environmental Factors

When it comes to environmental exposure, there’s one pressing area of emerging science: microplastic. These are plastic particles, smaller than about 5 millimeters, that permeate the world around us: they’re mixed into the soil, churning around in our oceans and waterways, and even float in the air [9].

Researchers say adults take in approximately 883 particles of microplastic every day—which works out to more than 322,000 particles per year [10]. And the study that reported this number includes a caveat that microplastic embedded in fruits, vegetables, and packaged meat products isn’t included in the calculation [10]. Other scientists tasked with estimating the amount of plastic in human waste report that the average person excretes 90,000 particles of microplastic every year [9].

The discrepancy between those two figures—microplastic in versus microplastic out—is noteworthy.

Here’s what experts know so far about the fate of ingested and inhaled microplastic. Ingested plastic bits larger than 150 microns—about the size of three grains of powdered sugar—stick to the mucus layer of the intestines where they encounter epithelial cells, the major protective barrier between the outside world and the interior of the body [9]. This may trigger local immune responses, including inflammation. The smallest plastic fragments—less than 150 microns—can cross the epithelial layer and enter circulating blood, eventually winding up in the liver, heart, lungs, or brain [9]. 

But eating plastic isn’t the only route of exposure. Microplastic bits float in the air, and people breathe in as many as 130 particles every day [9]. Once inhaled, these particles can travel from the lungs to the gut and then out to the tissues just like ingested particles [9]. The smallest bits can pass directly through the lungs’ epithelial layer to reach the circulating blood [9]. Or they might just embed in the lungs. Researchers found microplastic deep in human lungs for the first time just this year [11].

And that’s only microplastic. The smallest plastic particles are called nanoplastic, which clock in at less than 0.1 micron—about 1/3 the size of a single tobacco particle in cigarette smoke. These plastic particles are so small that they’re difficult to analyze, so most environmental data don’t include them [9].

Our ever-increasing exposure to those microplastic through ingestion or inhalation seems to cause similar issues as other environmental exposures: oxidative stress, inflammation, and a dysregulated microbiome with the potential to trigger immune, inflammatory, or metabolic disorders [9]. 

Sometimes the effects of microplastic go unnoticed until an infection tests the immune system. One animal study found that microplastic-fed mice who didn’t show obvious signs of microbiome or gut changes developed prolonged arthritis after exposure to a virus—a phenomenon the authors called “systemic immunopathological consequences” [12].

That’s worrisome in the context of an ongoing viral pandemic. Viral infection is already a known environmental factor that can lead to ANA, and COVID-19 has been shown to produce new-onset autoantibodies that are considered a hallmark symptom of long Covid [4,13]. 

More Work Needed

The past few years have seen an explosion in research around microplastic. Ten years ago, a PubMed search for “microplastic” generated just 35 studies. Today that same search yields 6,642 hits. That’s great news when it comes to unraveling any role this environmental exposure could play in the increase in autoimmune disease.

The authors of the recent ANA study say more research is required in order to get a handle on rising autoimmunity rates [3]. They recommend establishing a national registry for autoimmune diseases to make it easier to monitor changes in prevalence over time, pinpoint places with exceptional upticks in prevalence, and help understand the underlying causes and rising rates of autoimmunity [14].