type 1 Autoimmune polyendocrinopathy syndrome

Disorder that is characterized by the presence of 2 of 3 major clinical symptoms: ADDISON DISEASE, and/or HYPOPARATHYROIDISM, and/or CHRONIC MUCOCUTANEOUS CANDIDIASIS. MALABSORPTION SYNDROMES and DIARRHEA are also common. Germline mutations in the AIRE gene have been identified. OMIM: 240300

Also Known As:

Autoimmune polyendocrinopathy syndrome, type 1; Autoimmune Polyendocrinopathy Syndrome, Type I, Autosomal Dominant; Autoimmune Polyendocrinopathy Syndrome, Type I, With Reversible Metaphyseal Dysplasia; Autoimmune polyendocrine syndrome, type 1; Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED); Hypoadrenocorticism with hypoparathyroidism and superficial moniliasis; Polyglandular Deficiency Syndrome, Persian-Jewish Type

Networked: 93 relevant articles (2 outcomes, 3 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Autoimmune Diseases (Autoimmune Disease)
2.	Pure Red-Cell Aplasia
3.	Autoimmune Polyendocrinopathies (Schmidt Syndrome)
4.	Carcinogenesis
5.	Mycoses (Diseases, Fungus)

Experts

1.	Kämpe, Olle: 13 articles (06/2017 - 04/2003)
2.	Perheentupa, Jaakko: 12 articles (06/2017 - 04/2003)
3.	Husebye, Eystein S: 11 articles (06/2017 - 04/2003)
4.	Gustafsson, Jan: 9 articles (06/2017 - 04/2003)
5.	Ranki, Annamari: 8 articles (01/2022 - 03/2014)
6.	Peterson, Pärt: 6 articles (01/2022 - 01/2007)
7.	Betterle, Corrado: 6 articles (06/2017 - 04/2003)
8.	Meloni, Antonella: 5 articles (01/2019 - 10/2008)
9.	Kemp, E Helen: 5 articles (12/2018 - 06/2007)
10.	Krohn, Kai J E: 5 articles (12/2018 - 06/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to type 1 Autoimmune polyendocrinopathy syndrome:

1.	Rituximab (Mabthera)FDA Link 09/02/2008 - "A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)." 01/01/2012 - "Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab."
2.	Indicators and Reagents (Reagents)IBA 09/02/2008 - "A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)."
3.	Alemtuzumab (Campath)FDA Link 01/01/2022 - "[The efficacy of alemtuzumab for pure red cell aplasia associated with autoimmune polyendocrine syndrome type 1]."
4.	AutoantibodiesIBA 10/01/2000 - "The aim of the study was to assess the complex of autoantibodies which can be detected in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare autosomal recessive disease in which the extent of autoimmunity is still unknown. " 01/01/2022 - "Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare genetic syndrome caused by loss-of-function mutations of autoimmune regulator (AIRE), a key central tolerance mediator, leading to abnormal autoreactive T cell responses and autoantibody production. " 01/01/2021 - "Autoantibodies against IFN-α and IFN-ω are present in almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) caused by biallelic deleterious or heterozygous dominant mutations in AIRE. " 01/01/2019 - "In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), autoantibodies (AutoAbs) labeling brain neurons were reported; conversely, brain MRI alterations associated with these AutoAbs were never reported. " 01/17/2017 - "Pathogenic and Protective Autoantibodies in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)."
5.	Calcium-Sensing ReceptorsIBA 03/01/2014 - "Previous studies have identified the calcium-sensing receptor (CaSR) and NALP5 as parathyroid autoantibody targets in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). " 12/01/2009 - "Activating autoantibodies against the calcium-sensing receptor detected in two patients with autoimmune polyendocrine syndrome type 1." 06/01/2007 - "The calcium-sensing receptor is a target of autoantibodies in patients with autoimmune polyendocrine syndrome type 1." 12/01/2018 - "Calcium-Sensing Receptor Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1: Epitopes, Specificity, Functional Affinity, IgG Subclass, and Effects on Receptor Activity."
6.	Phosphotransferases (Kinase)IBA 01/01/2018 - "A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell-mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. "
7.	CytokinesIBA 01/01/2021 - "Cytokine-specific autoantibodies shape the gut microbiome in autoimmune polyendocrine syndrome type 1." 12/01/2018 - "The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features, new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary care centers." 12/01/2014 - "Autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy (APECED) is caused by mutations in the Autoimmune regulator (AIRE) gene and is associated with neutralizing anti-cytokine autoantibodies. " 02/01/2014 - "The relative roles of various autoantibodies against IL-17-type cytokines in susceptibility to chronic mucocutaneous candidiasis (CMC) in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) remain poorly defined. " 01/01/2014 - "Anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or thymic epithelial neoplasms. "
8.	AutoantigensIBA 03/17/2009 - "Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen." 03/06/2008 - "Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen." 04/01/2015 - "Autoimmune hepatitis in a murine autoimmune polyendocrine syndrome type 1 model is directed against multiple autoantigens." 01/01/2011 - "Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) or autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator (AIRE) gene, an important mediator of tolerance to self-antigens. " 05/01/2008 - "On the other hand and very interestingly, there are PIDs systematically associated with several autoimmune manifestations in which SLE has not been described, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX), and autoimmune lymphoproliferative syndrome (ALPS), suggesting that mechanisms considered as critical players for induction and maintenance of tolerance to autoantigens, such as (1) AIRE-mediated thymic negative selection of lymphocytes, (2) Foxp3+ regulatory T cell-mediated peripheral tolerance, and (3) deletion of auto-reactive lymphocytes by Fas-mediated apoptosis, could not be relevant in SLE physiopathology. "
9.	InterferonsIBA 07/21/2023 - "A hallmark of patients with autoimmune polyendocrine syndrome type 1 (APS-1) is serological neutralizing autoantibodies against type 1 interferons (IFN-I). " 06/27/2017 - "Assessment of autoantibodies to interferon-ω in patients with autoimmune polyendocrine syndrome type 1: using a new immunoprecipitation assay." 10/01/2008 - "Neutralizing autoantibodies to type I, but not type II, interferons (IFNs) are found at high titers in almost every patient with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a disease caused by AIRE gene mutations that lead to defects in thymic T-cell selection. " 10/01/2021 - "Almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) have neutralizing antibodies against type 1 interferons (IFN), important mediators of antiviral defense. " 09/17/2021 - "Break et al. (Research Articles, 15 January 2021, eaay5731) suggest that chronic mucocutaneous candidiasis in humans with inborn errors of AIRE and autoimmune polyendocrine syndrome type 1 is due to excessive interferon-γ production and not to autoantibodies neutralizing interleukin-17 cytokines. "
10.	AntibodiesIBA 06/30/2021 - "There was no argument for autoimmune polyendocrine syndrome type 1 so we concluded that it was isolated autoimmune hypoparathyroidism caused by activating antibodies to the CaSR. " 01/01/2015 - "On the other hand, anti-tryptophan hydroxylase-1 (TPH-1) antibodies are detected in autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED), a central tolerance defect, especially when complicated with gastrointestinal dysfunction. " 12/01/2000 - "Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by lack of functional products of the autoimmune regulator gene located on chromosome 21q22.3. The patients are at high risk of developing insulin-dependent (type 1) diabetes, but the positive predictive value of GAD65 or islet cell antibodies for type 1 diabetes is only 27%. " 08/14/1999 - "Tryptophan hydroxylase antibodies, associated with gastrointestinal disease in autoimmune polyendocrine syndrome type 1, are specific for this disease and not present in patients with other bowel disorders or healthy controls." 01/01/2020 - "The patient was seronegative for NALP5 and cytokine antibodies, indicating that their hypoparathyroidism was not a manifestation of autoimmune polyendocrine syndrome type 1. The etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid."

Therapies and Procedures

1.	Therapeutics 08/01/2007 - "To describe a patient with a history of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) who has experienced two episodes of noninfectious corneal ulceration with perforation that has been successfully managed with nonsurgical therapy. " 03/01/1999 - "Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder for which the gene (AIRE) has recently been identified on chromosome 21q22.3. We present the mutational analyses of a French-Canadian family with APECED, in which there are two affected siblings, as well as the response to cyclosporine A(CyA) therapy in the index patient, the eldest sibling. "
2.	Corneal Transplantation (Keratoplasty) 04/01/2001 - "Corneal pathology and outcome of keratoplasty in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)."