In Search for the Missing Link in APECED-like Conditions: Analysis of the AIRE Gene in a Series of 48 Patients

Autoimmune diseases are a heterogeneous group of disorders of the immune system.They can cluster in the same individual, revealing various preferential associations for polyendocrineautoimmune syndromes. Clinical observation, together with advances in genetics and theunderstanding of pathophysiological processes, has further highlighted that autoimmunity can beassociated with immunodeficiency; autoimmunity may even be the first primary immunodeficiencymanifestation. Analysis of susceptibility genes for the development of these complex phenotypes isa fundamental issue. In this manuscript, we revised the clinical and immunologic features and thepresence of AIRE gene variations in a cohort of 48 patients affected by high polyautoimmunity complexity,i.e., APECED-like conditions, also including patients affected by primary immunodeficiency.Our results evidenced a significant association of the S278R polymorphism of the AIRE gene withAPECED-like conditions, including both patients affected by autoimmunity and immunodeficiencyand patients with polyautoimmunity compared to healthy controls. A trend of association was alsoobserved with the IVS9+6 G>A polymorphism. The results of this genetic analysis emphasize theneed to look for additional genetic determinants playing in concert with AIRE polymorphisms. Thiswill help to improve the diagnostic workup and ensure a precision medicine approach to targetedtherapies in APECED-like patients.