Novel Insights into the Autoimmunity from the Genetic Approach of the Human Disease.

ABSTRACT

Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic inborn error of autoimmunity that is caused by damaging germline variants in the AIRE gene and clinically manifests with multiple autoimmune diseases in patients. Studies on the function of the AIRE gene, discovered in 1997, have contributed to fundamental aspects of human immunology as they have been important in understanding the basic mechanism of immune balance between self and non-self. This chapter looks back to the discovery of the AIRE gene, reviews its main properties, and discusses the key findings of its function in the thymus. However, more recent autoantibody profilings in APECED patients have highlighted a gap in our knowledge of the disease pathology and point to the need to revisit the current paradigm of AIRE function. The chapter reviews these new findings in APECED patients, which potentially trigger new thoughts on the mechanism of immune tolerance.