Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients

Abstract

APS1 in Sardinia is characterized by severe phenotype, marked clinical heterogeneity, and relative genetic homogeneity. The single AIRE mutation, R139X, and the anti-IFN-ω and IFN-α autoantibodies are helpful for earlier diagnosis, especially when APS1 presents unusually. HLA genotypes can modify the phenotype.

Mendelian Genetics of Human Susceptibility to Fungal Infection

“…It occurs worldwide but is most prevalent among Finnish, Sardinians, and Iranian Jews with estimated lifetime incidences of 1/ 25000, 1/14500, and 1/9000, respectively. More than 60 different AIRE mutations have been reported so far; the p.R257X nonsense mutation is most prevalent in Finland (.80%), the p.R139X nonsense mutation is most prevalent in Sardinia (.90%), the 13kb deletion c.967 -979del13bp is most common in North American and British patients, and the p.Y85C mutation is unique among Iranian Jews (Björses et al 1996;Heino et al 1999;Meloni et al 2012).…”

The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans

“…Experiments in nature suggest that patients with germ line mutations in STAT3 resulting in the complex clinical phenotype of hyper-IgE syndrome (HIES), AIRE mutation causing APS-1 and IL12Rβ1 deficiency causing increased susceptibility to atypical Mycobacteria and Salmonella are also susceptible to CMC [9][10][11][12][13]. Patients with these PIDs present with an impaired differentiation of IL17+CD4+ T cells (HIES and IL12Rβ1 deficiency) or increased production of anti-IL-17 antibodies (APS-1).…”

“…Several primary immunodeficiency disorders (PIDs) typically characterized by CMC and impaired IL-17-mediated immunity have been identified recently [9]. CMC in such patients may be part of a complex clinical phenotype exemplified by dominant negative signal transducer and activator of transcription (STAT)3 deficiency, interleukin (IL)-12Rβ1 and IL-12p40 deficiencies, and autoimmune polyendocrine syndrome (APS) type 1 [10][11][12][13]. In a subgroup of PIDs, predisposition to superficial candidiasis may be the only or the dominant characteristic of the underlying genetic disorder (CMC disease, CMCD) [9].…”

Is Autoimmunity or Insulin Resistance the Primary Driver of Type 1 Diabetes?

“…Mutations of AIRE, however, are implicated only in the rare polyglandular disorder of the autoimmune-polyendocrinopathycandidiasis-ectodermal dystrophy (APECED) syndrome, of which diabetes sometimes forms part [47]. Thus, dysregulation of the immune system by a single gene mutation can lead to autoimmunity as a primary cause of diabetes in man, as it can in the NOD mouse, but AIRE mutations are not found in nonsyndromic T1D [48] and do not seem relevant to the accelerator hypothesis.…”