ESPE Yearbook of Paediatric Endocrinology

Abstract: N Engl J Med. 2018 Jun 28;378(26):2543–2544.

In brief: This article reviews important developments and major advances in characterizing autoimmunity in patients with autoimmune polyendocrine syndromes, such as the identification of new autoantibody targets associated with distinct diseases and their manifestations. The authors also provide an up to date review of pathophysiological basis, investigations, management and future directions for patients with autoimmune polyendocrine syndromes.

Comment: Autoimmune polyendocrine syndromes are caused by loss of immune tolerance characterized by functional impairment of multiple endocrine glands. These syndromes can be broadly categorized as rare monogenic forms, such as autoimmune polyendocrine syndrome type 1 (APS-1), and the more common polygenic variety, autoimmune polyendocrine syndrome type 2 (APS-2). Autoimmune polyendocrine syndromes are characterized by circulating autoantibodies and lymphocytic infiltration of the affected tissues or organs, eventually causing organ failure. There is marked variability in clinical presentation in affected patients and their families, most likely due to a combination of genetic susceptibility and environmental factors.

This article reviews specific factors that are critical for maintaining immune tolerance, identification of new autoantibody targets associated with distinct diseases and discusses approaches for the appropriate diagnosis and longitudinal follow-up of affected patients. The authors conclude by presenting new directions for future management of Autoimmune polyendocrine syndromes by combining early and refined diagnostics with personalized genomics which would enable immunomodulatory therapy early in the autoimmune process to prevent irreversible organ damage.