Autoimmunity is a condition in which the body’s immune system reacts against its own healthy cells and tissues. A study conducted by scientists at the National Institutes of Health (NIH) and published online on April 7, 2020, in Arthritis and Rheumatology shows a concerning rise in the United States population of the presence of antinuclear antibodies (ANA), the most common biomarker of autoimmunity. Over the course of 25 years, the researchers found an overall 50 percent increase, but certain subgroups showed significantly higher rates than the rest of the population.
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The researchers studied the population at three different periods, each approximately 10 years apart.
- 1988 to 1991 There was an 11 percent frequency of ANA in the representative sample of the population of the United States.
- 1999 to 2004 That rose to 11.5 percent.
- 2011 to 2012 The rate was around 16 percent. The most dramatic increase occurred from the second to the third time period.
Biggest Autoimmunity Biomarker Increases Found in Specific Subgroups
The biggest increases in ANA were seen in adolescents, males, non-Hispanic whites, and adults over the age of 50. Adolescents showed a twofold increase in the second period compared with the first period and a threefold increase in the third period compared with the first period. “A threefold increase in adolescents is roughly twice the rate of increase seen in the overall population and was the largest subgroup increase we saw. It’s the most worrisome because of the lifelong impact of immune dysregulation in these relatively young people,” says one of the study's coauthors, Frederick Miller, MD, PhD, the deputy chief of the clinical research branch at the National Institute of Environmental Health Sciences (NIEHS), part of NIH.
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Reasons for the Rise Are Still Unclear
The study accounted for factors such as BMI, smoking, and drinking alcohol. What is driving the rapid increases? “That's the million-dollar question, of course, and what we're trying to figure out through other studies,” says Dr. Miller. “Since our genes haven't changed that much in the last several decades to account for this, this has to be due to changes in our lifestyles, some exposures, or some other environmental factors that impact the immune system, but we don’t know exactly what they are. It may be that each gender or each age group has entirely different risk factors, but we don’t know that yet. That's why we are doing further studies now, to try to understand which of these different factors that have changed in the last 25 years are responsible for these autoimmune changes in different individuals.”
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For example, a study published in Journal of the American Medical Association in June 2018 found that stress-related disorders, such as post-traumatic stress disorder (PTSD) or adjustment disorder, were significantly associated with risk of subsequent autoimmune disease.
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Autoimmunity Markers Don’t Automatically Cause Autoimmune Disease
Autoimmunity is distinct from autoimmune disease. Autoimmune diseases (rheumatoid arthritis, lupus, multiple sclerosis, ankylosing spondylitis, type 1 diabetes, psoriasis, and psoriatic arthritis) are autoimmunity plus pathology. You can have autoimmunity without autoimmune disease, but when you have autoimmune disease, you usually have autoimmunity. “The challenge that we have today is we do not know for sure that you would necessarily get a disease as a result of having an ANA marker,” explains Miller.
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Don’t Get Overanxious if You Have the ANA Marker
Vinicius Domingues, MD, a rheumatologist and a medical adviser to the digital patient advocacy and education arthritis community CreakyJoints, points out that around 5 to 10 percent of the population are positive for the ANA marker, which equates to 20–25 million Americans. “We know we don't have that many people sick, so maybe those results should be read by an expert in context. Every single positive doesn’t mean a diagnosis. We have to look at the broader picture and not just the blood test. The question is, could an expressed ANA today mean disease 10 years from now? Yes, but it doesn’t mean you have it now,” he says.
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What Does the Biomarker Increase in the Population Mean?
These results are concerning because there's increasing evidence that these antibodies may precede or even predict the development of autoimmune diseases later in life. “That’s not always the case, but when that does happen, it suggests that there may be an increased frequency of these autoimmune diseases in the future. In fact, current findings suggest that the immune abnormality that relates to autoimmunity often evolves into an autoimmune disease,” says Miller.
Future Research Will Look at Causes and How to Prevent Autoimmune Disease
The researchers hope that, with further study, they will someday move the autoimmune diseases into the theater of disease prediction based on risk factors. Miller says, “Cardiovascular diseases and cancers have now been associated with many risk factors that physicians can use to create preventive approaches to try to avoid future disease. I'm hoping that future studies that we and others are doing will allow similar predictive models for autoimmune diseases. The next goal for autoimmunologists is to become preventionists: to identify risk factors so we can prevent the development of future autoimmune diseases.”