I have been waiting for an article like this to be published. It’s finally arrived!! Anecdotal experiences from my very own life have evolved the following pet theory: presence of an antigen during a non-related immune response induces autoimmunity. Philosophically, cross-reactive immune response made perfect sense. All I needed was a pesky little thing called evidence.
Thanks to a massive collaboration between 9 institutions, the data is real. Typically, autoimmune disease is attributed to environmental or heredity sources. Imperfect T or B cell maturation in the thymus or bone marrow, respectively, leads to errant self-antigen reaction. While infectious disease has been implicated in the development of autoimmune disease, the molecular evidence has been lacking. The current report, published this month in Science, shows a specific connection between asymptomatic reovirus infection with the development of celiac disease (CeD).
Celiac disease is a complicated syndrome involving disruption of oral tolerance and gluten autoimmunity. Typically, oral tolerance suppresses an immune reaction to the antigens (aka food) that we eat through activation of regulatory T cells. Regulatory T cells directly repress helper T cells, which are a subset of T cells that initiate a cascade of immune activation. Using mouse models, researchers defined a pathway in which reovirus stimulates helper T cells to react with orally-administered antigens. Using models of WT and CeD-predisposed mice, researchers also demonstrated that reovirus infection induces biochemical reactions that set the stage for CeD development. Specifically, activation of an enzyme called transglutaminase 2 (TG2), which is thought to alter the gluten peptide to a more reactive form, only occurred in CeD-predisposed mice infected with reovirus.
Importantly, reovirus is a subclinical gastrointestinal infection that is easily cleared by the immune system. Therefore, attempting to correlate the virus in the gut of established celiac disease patients would be unsuccessful. Controlled studies investigating direct effects of acute infection on autoimmunity are required. This research supports the growing hypothesis that celiac disease, along with other serious and complicated gut disorders, such as colitis and Crohn’s disease, are tightly interconnected with a microbial immune response. Further dissection of the steps that lead to the complexity of these disorders will hopefully lead to more effective and intelligently-designed preventions and treatments.
And I’M excited by this finding because one sweltering 4th of July, I developed a metal allergy after experiencing a particularly dreadful heat rash while wearing a necklace. I only have an n=1 for linking cross-reactive immune response to an unrelated antigen but as I wrote this blog post, I learned something, which is all a scientist-at-heart can hope for. This cross-reactive hypothesis between infection/allergies and autoimmunity is not novel. It’s been studied for years! How wonderful.
Thanks to Joel Tamayo for the Corona. Enjoy happy hour, y’all!