Unless you’re an identical twin, you probably won’t often be confused with someone else. In the same way, our own sense of self, different from all other humans, is deeply rooted in early childhood.
The immune system, however, faces much greater challenges in distinguishing itself from the non-self. If this complex surveillance network does not identify a foreign intruder, such as a bacterium or a virus, the result may be a serious, uncontrolled disease.
Under certain circumstances, however, the immune system may become overly vigilant, identifying our own tissues as foreign and targeting their destruction, leading to autoimmune diseases. Autoimmune responses are also associated with some cancers.
In a new study, Arizona State University researcher Joshua LaBaer and colleagues explore components of the immune system known as autoantibodies. Although they have been implicated as key players in a number of serious autoimmune diseases, the study notes that autoantibodies are also found in healthy individuals.
This may make the diagnostic use of autoantibodies as sentinels of autoimmune disease more difficult, hence the importance of such research.
A better awareness of the generalization and role of autoantibodies in human health and disease can ultimately help in the design of better diagnoses and therapies against a number of diseases.
Historically, we have looked for autoantibodies present only in diseases, but we have always been intrigued because our healthy controls always had autoantibodies. So we decided to see if any of these “healthy autoantibodies” were common in healthy people and I’m sure many of them were. Knowing this will help us avoid confusion in future studies. “
Joshua LaBaer, a researcher at Arizona State University
Dr. LaBaer is the executive director of the Biodesign Institute at ASU, as well as the director of the Biodesign Virginia G. Piper Center for Personalized Diagnostics.
The results of the research appear in the current issue of the journal Cell Reports.
Biological Civil War
Autoimmune diseases are a widespread phenomenon, affecting approximately 23 million Americans. Researchers have identified more than 80 autoimmune diseases, including two common diseases such as type 1 diabetes, lupus, multiple sclerosis and rheumatoid arthritis, as well as darker diseases, which are often difficult to diagnose correctly. Nearly 80% of autoimmune diseases occur in women, for reasons that researchers are still trying to figure out.
Science has a lot to learn about the underlying mechanisms responsible for autoimmune reactions. These diseases often arise after infections. Two major components of the so-called adaptive immune system also play an important role in autoimmunity. These are white blood cells or lymphocytes, known as T cells and B cells. Lymphocytes are crucial to maintaining health and are essential for survival. These sentries, who are constantly patrolling the bloodstream, 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 enter to destroy them. Antibodies operate by binding to pathogens or foreign substances, including toxins, and neutralizing their harmful effects. If an antibody binds to a virus, for example, it can prevent the intruder 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 defense arsenal is exquisitely sensitive to foreign proteins, peptides, enzyme complexes, RNA, and DNA. When these are found, B cells can take action, producing antibodies directed against these foreign entities.
Mutiny immunity
The immune system, however, faces a formidable challenge. B and T cells must be able to accurately target threats to the body while remaining harmless to host cells and tissues. Immune cells are not born with this knowledge, they learn it in a matter of weeks, receiving training in a kind of biological classroom, where they undergo two rounds of careful screening.
Successfully graduated B and T cells from their training sessions have two types of immune tolerance, central immune tolerance, which develops in the bone marrow, and peripheral immune tolerance, which matures in the ganglia. lymphatics.
After training, the cells that show immune tolerance, a kind of non-aggression pact with healthy tissues, are kept in the body for future use. Immune cells that have stopped training and are at risk of autoimmunity are hijacked or destroyed.
However, sometimes pathogens or cancers can produce antigens that bear such close resemblance in terms of sequence or structure to the characteristics found in normal body tissues that host tissues are confused with disease antigens. and target antibodies. These characteristics are known as autoantigens, and the antibodies produced to target them are known as autoantibodies.
The misalignment of autoantigens due to their similarities to disease antigens is known as molecular mimicry and is implicated in many autoimmune disorders, from rheumatoid arthritis to multiple sclerosis.
Antibody hunting
The new study explores common autoantibodies-; those that occur in healthy individuals. Although these common autoantibodies do not appear to cause disease, they do occur in up to 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 scanning common autoantibodies is a device known as a protein microarray. Here, thousands of individual proteins are placed in a glass slide. When a blood sample spreads through the microarray, the antibodies (in this case, the autoantibodies) bind to specific protein antigens.
The microarrays underwent two rounds of screening. In the first round, 182 blood samples from healthy individuals with 7,653 human proteins were examined. In the second round, 90 blood samples were examined against 1,666 human proteins. The experiments identified a total of 77 common autoantibodies.
Blood samples came from healthy individuals of both sexes, ranging in age from childhood to 84 years. The results showed that the number of autoantibodies increased from birth to adolescence and then stagnated. In addition, the number of autoantibodies detected was the same regardless of gender, a surprising result given the large disparity between men and women in the prevalence of autoimmune diseases.
Another underlying riddle is why common autoantibodies do not produce autoimmune diseases. Although these antibodies appear to have evaded the screening process leading to immune tolerance, their appearance on the body remains benign. Autoimmune pathology is thought to require autoantibodies to bind and form complexes with autoantigens, and this can be blocked in the case of common autoantibodies.
Future research promises to unlock many more secrets about the nature of autoantibodies. The current study looked at less than half of all human proteins. Most likely, additional common autoantibodies remain to be discovered.
Source:
Magazine reference:
Shome, M., et al. (2022) Serum autoantibodies reveal that healthy individuals share common autoantibodies. Cellular reports. doi.org/10.1016/j.celrep.2022.110873.