With an estimated 50 million afflicted in the US alone, autoimmune diseases consume an increasing share of global morbidity and health care costs. While a healthy immune system maintains
tolerance to innocuous antigens (body's own/self and microbiota antigens, for example), selective immune attack on body's own antigens
disrupts this process in autoimmunity.
Autoimmune disease-prone individuals display
auto-antigen selectivity, and no specific auto-antigen represents an universal target of autoimmune attacks. Current approaches to autoimmune diseases are inadequate to explain such auto-antigen selectivity. After all, failure of innate “training” of the adaptive immune system due to reduced exposure to pathogen-associated molecular patterns
(PAMPs) should lead to “total body” autoimmunity rather than selective autoimmune diseases.
Tregeutix we are developing a novel discovery framework dubbed
SPIRAL that reveals how Tregs cross-reactive to specific microbiota-derived antigens control tolerance to cryptic autoantigens. Analysis of data through SPIRAL uncovers a predictable relationship between
“holes” in Treg repertoire specific for antigens (epitopes) cross-reactive between microbiota, cryptic self and environmental antigens that dictates the type of autoimmune disease.
SPIRAL allows systematic discovery of specific members of microbiota involved in protection against autoimmune diseases.