scholarly journals Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I

2009 ◽  
Vol 265 (5) ◽  
pp. 514-529 ◽  
Author(s):  
E. S. Husebye ◽  
J. Perheentupa ◽  
R. Rautemaa ◽  
O. Kämpe
Keyword(s):  
Clinical Manifestations ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Polyendocrine Syndrome

scholarly journals Mutational analysis of the autoimmune regulator (AIRE) gene in sporadic autoimmune Addison's disease can reveal patients with unidentified autoimmune polyendocrine syndrome type I

2002 ◽  
pp. 519-522 ◽  
Author(s):  
AS Boe ◽  
PM Knappskog ◽  
AG Myhre ◽  
JI Sorheim ◽  
ES Husebye
Keyword(s):  
Mutational Analysis ◽  
Clinical Manifestations ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Common Mutation ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Regulator ◽  
Aire Gene ◽  
Autoimmune Polyendocrine Syndrome

OBJECTIVE: To investigate whether patients with Addison's disease and polyendocrine syndromes have undiagnosed autoimmune polyendocrine syndrome type I (APS I). MATERIALS AND METHODS: Forty patients with clinical manifestations resembling APS I and with autoantibodies typical of this condition were screened for Norwegian autoimmune regulator (AIRE) gene mutations. RESULTS: A 30-year old man who had developed Addison' s disease at the age of 12, but had no other components of APS I, was homozygous for the 1094-1106 deletion mutation in exon 8 of the AIRE gene, the most common mutation found in Norway. CONCLUSIONS: APS I patients with milder and atypical phenotypes are difficult to diagnose on clinical grounds. Autoantibody analysis and mutational analysis of AIRE may therefore be helpful modalities for identifying these individuals.

scholarly journals The Transcription Factors SOX9 and SOX10 Are Vitiligo Autoantigens in Autoimmune Polyendocrine Syndrome Type I

2001 ◽  
Vol 276 (38) ◽  
pp. 35390-35395 ◽  
Author(s):  
Håkan Hedstrand ◽  
Olov Ekwall ◽  
Mats J. Olsson ◽  
Eva Landgren ◽  
E. Helen Kemp ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Polyendocrine Syndrome

scholarly journals Transcriptional Changes in Regulatory T Cells From Patients With Autoimmune Polyendocrine Syndrome Type 1 Suggest Functional Impairment of Lipid Metabolism and Gut Homing

2021 ◽  
Vol 12 ◽  
Author(s):  
Amund Holte Berger ◽  
Eirik Bratland ◽  
Thea Sjøgren ◽  
Marte Heimli ◽  
Torgeir Tyssedal ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Type I ◽  
Syndrome Type ◽  
Functional Studies ◽  
Autoimmune Polyendocrine Syndrome ◽  
Organ Specific ◽  
Hla Dqa1 ◽  
And Function ◽  
The Impact

Autoimmune polyendocrine syndrome type I (APS-1) is a monogenic model disorder of organ-specific autoimmunity caused by mutations in the Autoimmune regulator (AIRE) gene. AIRE facilitates the expression of organ-specific transcripts in the thymus, which is essential for efficient removal of dangerous self-reacting T cells and for inducing regulatory T cells (Tregs). Although reduced numbers and function of Tregs have been reported in APS-I patients, the impact of AIRE deficiency on gene expression in these cells is unknown. Here, we report for the first time on global transcriptional patterns of isolated Tregs from APS-1 patients compared to healthy subjects. Overall, we found few differences between the groups, although deviant expression was observed for the genes TMEM39B, SKIDA1, TLN2, GPR15, FASN, BCAR1, HLA-DQA1, HLA-DQB1, HLA-DRA, GPSM3 and AKR1C3. Of significant interest, the consistent downregulation of GPR15 may indicate failure of Treg gut homing which could be of relevance for the gastrointestinal manifestations commonly seen in APS-1. Upregulated FASN expression in APS-1 Tregs points to increased metabolic activity suggesting a putative link to faulty Treg function. Functional studies are needed to determine the significance of these findings for the immunopathogenesis of APS-1 and for Treg immunobiology in general.

scholarly journals Clinical and Genetic Characteristics of COL2A1-Associated Skeletal Dysplasias in 60 Russian Patients: Part I

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 137
Author(s):  
Tatyana Markova ◽  
Vladimir Kenis ◽  
Evgeniy Melchenko ◽  
Darya Osipova ◽  
Tatyana Nagornova ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Normal Growth ◽  
Type I ◽  
Syndrome Type ◽  
Stickler Syndrome ◽  
Genetic Characteristics ◽  
Col2a1 Gene ◽  
Skeletal Dysplasias ◽  
Spondyloepiphyseal Dysplasia ◽  
Novel Variants

The significant variability in the clinical manifestations of COL2A1-associated skeletal dysplasias makes it necessary to conduct a clinical and genetic analysis of individual nosological variants, which will contribute to improving our understanding of the pathogenetic mechanisms and prognosis. We presented the clinical and genetic characteristics of 60 Russian pediatric patients with type II collagenopathies caused by previously described and newly identified variants in the COL2A1 gene. Diagnosis confirmation was carried out by new generation sequencing of the target panel with subsequent validation of the identified variants using automated Sanger sequencing. It has been shown that clinical forms of spondyloepiphyseal dysplasias predominate in childhood, both with more severe clinical manifestations (58%) and with unusual phenotypes of mild forms with normal growth (25%). However, Stickler syndrome, type I was less common (17%). In the COL2A1 gene, 28 novel variants were identified, and a total of 63% of the variants were found in the triple helix region resulted in glycine substitution in Gly-XY repeats, which were identified in patients with clinical manifestations of congenital spondyloepiphyseal dysplasia with varying severity, and were not found in Stickler syndrome, type I and Kniest dysplasia. In the C-propeptide region, five novel variants leading to the development of unusual phenotypes of spondyloepiphyseal dysplasia have been identified.

scholarly journals Autoimmune polyendocrine syndrome type I in Slovakia: relevance of screening patients with autoimmune Addison's disease

2008 ◽  
Vol 158 (5) ◽  
pp. 705-709 ◽  
Author(s):  
Ng'weina F. Magitta ◽  
Mikuláš Pura ◽  
Anette S Bøe Wolff ◽  
Peter Vanuga ◽  
Anthony Meager ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Monogenic Disease ◽  
Adrenal Crisis ◽  
Addison's Disease ◽  
Type I ◽  
Syndrome Type ◽  
Exon 2 ◽  
Clinical Criteria ◽  
Autoimmune Polyendocrine Syndrome ◽  
Major Mutation

BackgroundAutoimmune polyendocrine syndrome type I (APS I) is a monogenic disease affecting endocrine glands and other organs due to mutations of the autoimmune regulator (AIRE) gene. There is a wide variability in clinical phenotypes in patients with APS I, which makes the diagnosis a challenge.ObjectiveTo screen for APS I among Slovakian patients with sporadic Addison's disease and clinical features that raised the suspicion of APS I.MethodsAll 14 exons and exon–intron boundaries of the AIRE gene were sequenced. In addition, autoantibodies specific for Addison's disease and polyendocrine syndromes were assayed.ResultsUsing clinical criteria we identified four patients with APS I in three families. Two patients had a novel missense mutation in exon 2 (c.274C>T, p.R92W) and either the Finnish major mutation (c.769C>T) or the common 13 bp deletion (c.967–979del13bp). APS I was diagnosed in a brother of the latter after his death due to an adrenal crisis. A fourth patient had primary adrenal failure and hypoparathyroidism without AIRE mutations or APS-I specific autoantibodies.ConclusionsFour patients with APS I were found in a Slovakian cohort of Addison patients, although the lack of detectable AIRE mutations and APS I-specific autoantibodies raises uncertainty regarding the pathogenesis in one of the patients. This study demonstrates the merits of screening patients with phenotypic features or autoantibody findings that could indicate APS I, even in adult patients. It is necessary to identify APS I patients in order to provide appropriate treatment and follow-up of the various components of APS I.

Psoriasis vulgaris and autoimmune polyendocrine syndrome type I: a case report

2014 ◽  
Vol 27 (7-8) ◽  
Author(s):  
Atilla Cayir ◽  
Ragıp Ismail Engin ◽  
Mehmet Ibrahim Turan ◽  
Erdal Pala
Keyword(s):  
Case Report ◽  
Psoriasis Vulgaris ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Polyendocrine Syndrome

scholarly journals Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I

2010 ◽  
Vol 207 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Anne Puel ◽  
Rainer Döffinger ◽  
Angels Natividad ◽  
Maya Chrabieh ◽  
Gabriela Barcenas-Morales ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Chronic Mucocutaneous Candidiasis ◽  
Type I ◽  
Syndrome Type ◽  
Mucocutaneous Candidiasis ◽  
Autoimmune Polyendocrine Syndrome ◽  
Clinical Syndromes ◽  
Macrophage Colony ◽  
Factor Α

Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-γ, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1β, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-β, tumor necrosis factor [α], or transforming growth factor β). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.

scholarly journals Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1

2021 ◽  
Vol 218 (7) ◽  
Author(s):  
Paul Bastard ◽  
Elizaveta Orlova ◽  
Leila Sozaeva ◽  
Romain Lévy ◽  
Alyssa James ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Type I Interferons ◽  
Type I ◽  
Syndrome Type ◽  
Loss Of Function ◽  
Type I Ifns ◽  
Autoimmune Polyendocrine Syndrome ◽  
Life Threatening ◽  
Very High

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti–IFN-β and another anti–IFN-ε, but none had anti–IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.

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