Autoimmune Disease-New Theories

Scientific American September 2021 pp34-40 |The Body Against Itself|”How Auto-Immunity Starts” “New research indicates body organs under stress may attract attackers from the immune system” by Stephani Sutherland

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“What we know now is that target tissue is not merely a bystander; it’s an active participant” says Sonia Sharma (La Jolla Institute for Immunology)

We have long known that type 1 diabetes is triggered in childhood by our own immune system. Cells of the immune system attack the insulin-making cells, (Beta Cells), within the pancreas. Without Insulin we cannot effectively control sugar levels vital for normal metabolism. A long accepted dogma was that a mechanism dubbed molecular mimicry was the root cause of this form of diabetes. In molecular mimicry it was thought that proteins or other molecules from viral or other infections attached to the pancreas. In this mechanism, circulating antibodies tagged these cells for destruction or the cells were directly attacked by cytotoxic T cells. It was a theory that was at least consistent with the knowledge at the time and the signs and symptoms of the disease.

The current theory now suggests that “beta cells in people with diabetes produce heightened amounts of molecules that T cells use as targets.” Two molecules that are featured in this model are the insulin precursor molecule known as preproinsulin (PPI) and an undefined class 1 major histocompatibility antigen (MHC). MHC molecules are present on all cell types and the immune system is taught early to not target them for destruction. PPI mostly is sequestered inside cells normally so some killer T cells that are reactive to PPI are not excluded from our immunological systems. It is this combination of PP1 and MHC that become targeted by killer T cells “under stress.” In stress, beta cells release signaling molecules known as chemokines that actually “pull immune cells to them.”

Another area of research that is helping us understand autoimmune disease is GWAS short for Genome Wide Association Studies. GWAS of biopsies from diseased tissue have “found that more than 80 percent of identified genetic variants were expressed by target cells in type 1 diabetes and three other autoimmune diseases: multiple sclerosis, lupus and rheumatoid arthritis. The “top genes showing extra activity were those related to interferons a class of proinflammatory cytokines that cells release to flag down immune cells when there is a problem such as a viral infection.”

Other studies have discovered that the cells affected by autoimmune disease share three characteristics. The cells “reside in glands” making hormones “at high rates” which stresses cells, these cells release hormones directly into the blood-stream and these tissues are “penetrated by lots of blood vessels. These features promote a way to activate immune responses at the local tissue level and beyond.

In recent years there has also been the observation that autoimmune disease is increasing in frequency. Two ideas have emerged. First, some clever population studies suggest that early exposure to the broader environment may diversify our intestinal bacteria and keep autoimmune disease at lower levels. Second, new environmental triggers may be in play. It is noted that over the last few decades “approximately 80,000-90,000 new chemicals have been approved for use...and we have a completely different diet.”