Unless you are identical twins, you are probably not often mistaken for someone else. Likewise, unlike any other human being, our own sense of self is deeply rooted since early childhood.
However, the immune system faces much greater challenges in distinguishing the self from the non-self. Should this complex surveillance network fail to identify a foreign invader, such as a bacteria or virus, the result could be a serious, uncontrolled disease.
However, under certain circumstances, the immune system can become too vigilant, identifying our own tissues as foreign and targeting them for destruction, resulting in an autoimmune disease. Autoimmune reactions are also associated with some cancers.
In a new study, Arizona State University researcher Joshua LaBaer and colleagues examine components of the immune system known as: autoantibodies† Although they have been implicated as central players in a range of serious autoimmune diseases, the study finds that autoantibodies are also found in healthy individuals.
This fact may make the diagnostic use of autoantibodies as sentinels of autoimmune disease more challenging, hence the importance of such studies.
A better awareness of the ubiquity and role of autoantibodies in human health and disease could ultimately help design better diagnostics and therapies against a range of diseases.
Historically, we’ve looked for autoantibodies that only appear in disease, but we’ve always been intrigued because our healthy controls always had autoantibodies, too. So we decided to see if any of these “healthy autoantibodies” were common in healthy people, and there certainly were a lot of them. Knowing this will help us avoid confusion in future studies.”
Joshua LaBaer, Researcher, Arizona State University
dr. LaBaer is the Executive Director of ASU’s Biodesign Institute and the Director of the Biodesign Virginia G. Piper Center for Personalized Diagnostics.
The research results appear in the current issue of the journal Mobile Reports†
biological civil war
Autoimmune diseases are a widespread phenomenon, affecting approximately 23 million Americans. Researchers have identified more than 80 autoimmune diseases, including common conditions such as type 1 diabetes, lupus, multiple sclerosis and rheumatoid arthritis, as well as more obscure conditions, which often prove challenging to diagnose correctly. Nearly 80% of autoimmune diseases occur in women, for reasons researchers are still trying to figure out.
Science still has a lot to learn about the underlying mechanisms responsible for autoimmune responses. Often such diseases arise after infections. Two primary components of the so-called adaptive immune system also play an important role in autoimmunity. These are the white blood cells or lymphocytes, also known as: T cells and B cells. Lymphocytes are critical to maintaining health and essential for survival. These sentries, patrolling the bloodstream incessantly, are alerted by the presence of foreign entities known as antigens.
T cells protect against infection by pathogens such as bacteria, viruses and fungi. They can also attack and destroy cancer cells. B cells secrete proteins known as antibodies that disrupt interactions or target infected cells so that other cells can come in to destroy them. Antibodies work by binding to pathogens or foreign substances, including toxins, and neutralizing their harmful effects. For example, if an antibody binds to a virus, it can prevent the invader from entering a normal cell to cause an infection. B cells can also recruit other specialized immune cells to migrate to the sites of infected cells and help destroy them.
The immune system’s defensive arsenal is extremely sensitive to foreign proteins, peptides, enzyme complexes, RNA and DNA. When encountered, B cells can spring into action and produce antibodies directed against these foreign entities.
However, the immune system faces a huge challenge. B and T cells must be able to accurately address threats to the body and remain harmless to host cells and tissues. Immune cells are not born with this knowledge, they learn it in a few weeks and receive training in a kind of biological classroom, where they undergo two rounds of careful screening.
The B and T cells that successfully complete their training sessions exhibit two types of immune tolerance, central immune tolerance, which develops in the bone marrow, and peripheral immune tolerance, which matures in the lymph nodes.
After their training, cells that exhibit immune tolerance, a kind of non-aggression pact with healthy tissues, are stored in the body for future use. Immune cells that drop out of training and pose a risk of autoimmunity are sequestered or destroyed.
But sometimes pathogens or cancers can produce antigens so closely related in sequence or structure to features found in normal tissues in the body that the host tissues are mistaken for disease antigens and are the target of antibodies. Such features are known as self-antigens and the antibodies produced to target them are known as autoantibodies.
The mistargeting of self-antigens because of their similarities to disease antigens is known as molecular mimicry and has been implicated in many autoimmune diseases, from rheumatoid arthritis to multiple sclerosis.
Quest for Antibodies
The new study examines common autoantibodies; that occur in healthy individuals. While these common autoantibodies do not appear to cause disease, they occur in as many as 40% of people tested. It is likely that at least some of these common autoantibodies have been misidentified as disease antibodies.
The researchers performed a meta-analysis of 9 data sets. The tool of choice for investigating the common autoantibodies is a device known as a protein microarray. Here thousands of individual proteins are attached to a glass slide. When a blood sample is spread across the microarray, antibodies (in this case, autoantibodies) bind with specific protein antigens.
The microarrays were subjected to two rounds of screening. In the first round, 182 blood samples from healthy individuals were screened for 7,653 human proteins. In the second round, 90 blood samples were screened for 1,666 human proteins† The experiments identified a total of 77 common autoantibodies.
The blood samples were from healthy individuals of both sexes, ranging in age from infancy to 84 years old. The results showed that the number of autoantibodies increased from birth through adolescence and then stabilized. Furthermore, the number of autoantibodies detected was the same regardless of gender, a surprising finding given the large gender disparity in the prevalence of autoimmune diseases.
Another underlying conundrum is why common autoantibodies don’t produce autoimmune disease. While such antibodies appear to have evaded the screening process that leads to immune tolerance, their occurrence in the body remains benign. It is believed that autoimmune pathology requires autoantibodies to bind and form complexes with autoantigens, and this can be blocked in the case of common autoantibodies.
Future research promises to unravel many more secrets about the nature of autoantibodies. The current study examined less than half of all human proteins. Most likely, other common autoantibodies have yet to be discovered.
Shom, M., et al. (2022) Serum autoantibodyoma reveals that healthy individuals share common autoantibodies. Mobile Reports† doi.org/10.1016/j.celrep.2022.110873†
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