Patients are diagnosed with an autoimmune disease based on the presence of antibodies in their blood. These antibodies are Y-shape proteins created by the immune system to identify and neutralize microbes. For decades, antibodies have been detected in patients with a range of autoimmune conditions. However, this antibody production was first discovered nearly a century before humans were understood to harbor a microbiome. The human body was instead considered to be largely sterile. This meant that if an antibody was detected in a patient with an autoimmune condition, its creation could not be tied to the presence of a microbe.

Researchers were subsequently forced to develop the theory of autoimmunity. The theory contends that in patients with autoimmune disease, “autoantibodies” are created in response to human proteins rather than microbes. In other words, the immune system is hypothesized to become dysregulated and attack its own tissue.

However, now that thousands of novel microbes and viruses have been identified in human tissue and blood, the theory of autoimmunity must be re-evaluated. Increasing evidence suggests that  “autoantibodies” are actually normal antibodies created in response to many of these previously undetected microbes and viruses. In other words, the “autoantibodies” often detected in patients with inflammatory disease may simply be antibodies generated in response to pathogens in the microbiome.

Indeed, a growing number of studies show that so called “autoantibodies” are often generated in response to microbes. For example, high levels of the “autoantibody” rheumatoid factor have been detected not only in patients with rheumatoid arthritis, but also in patients with a number of bacterial, viral, and parasitic infections.

However, some of these “autoantibodies” may still be capable of targeting human tissue. This is because antibodies are very polyspecific. Simply put, antibodies identify their microbial targets by recognizing their specific sizes and shapes. But these antibodies are created in a flexible manner allowing them to also target proteins that are similar but not identical to their intended target. Some of these similar proteins may be human in origin.

It follows that an antibody created in response to a microbial protein may target a similar human protein by mistake. Subsequent “collateral damage” results in additional inflammation of human tissue. For example, an Australian research team found that when normal individuals were injected with tetanus toxoid (created by a microbe), at least seven antibodies were produced. While six of these antibodies correctly targeted the tetanus bacterium, one of them targeted the human protein cardiolipin.

As described in this article, it is extremely common for microbes in the human body to create proteins that are very similar to those of their human hosts. This means there is ample opportunity for antibodies created in response to microbes to additionally target human tissue.

In addition, “autoantibodies” are frequently detected in patients months or years before the onset of specific disease symptoms. This reflects the gradual increase in microbiome dysbiosis characteristic of successive infection, and further supports the possibility that “autoantibodies” are created in response to accumulating microbes.