scholarly journals Mild COVID-19 despite autoantibodies to type I IFNs in Autoimmune-Polyendocrine-Syndrome Type 1 (APS-1)

2021 ◽  
Author(s):  
Christian Meisel ◽  
Bengisu Akbil ◽  
Tim Meyer ◽  
Erwin Lankes ◽  
Victor M. Corman ◽  
...  
Keyword(s):  
Type I ◽  
Syndrome Type ◽  
Type I Ifns ◽  
Autoimmune Polyendocrine Syndrome

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.

scholarly journals Autoantibodies to 21-hydroxylase as a diagnostic marker of primary autoimmune adrenal insufficiency, including at its potential and latent stages

2020 ◽  
Vol 48 ◽  
Author(s):  
N. F. Nuralieva ◽  
M. Yu. Yukina ◽  
E. A. Troshina ◽  
N. M. Malysheva ◽  
L. V. Nikankina
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Immune Tolerance ◽  
Type I ◽  
Syndrome Type ◽  
Type Ii ◽  
Autoimmune Polyendocrine Syndrome ◽  
Group 2

Rationale: In Russia, assessment of anti-P450c21 antibodies (AB) in the diagnosis of autoimmune adrenal insufficiency (AAI) has not been commonly used, and the disease screening has not been implemented.Aims: 1) To determine the sensitivity and specificity of anti-P450c21 AB determination in the AAI diagnosis; 2) To estimate the prevalence of anti-P450c21 AB carriage in patients without AAI.Materials and methods: Anti-P450c21 AB were assessed in 40 patients (group 1) with manifest AAI; 171 patients without established diagnosis of AAI, including 113 subjects with autoimmune thyroid disorders or type 1 diabetes mellitus (AID, group 2); 25 carriers of AB markers of thyroid AID and/or type 1 diabetes mellitus without any target organ dysfunctions (group 3); 33 patients with non-autoimmune endocrine disorders (group 4), and 25 healthy individuals (group 5).Results: Determination of anti-P450c21 AB for the diagnosis of AAI had 95% sensitivity, with specificity of 100%, predictive value of a positive result of 100%, and predictive value of a negative result 92.6%. Anti-P450c21 AB were inversely correlated with the duration of glucocorticoid replacement therapy (r = -0.222, p < 0.05). High levels of anti-P450c21 AB were found in 4 (3.5%) patients of group 2; based on the results of additional hormonal testing, 50% cases were diagnosed with the latent stage of the disease and 50% cases with the potential stage.Discussion: The sensitivity of the anti-P450c21 AB determination for AAI diagnosis in our study was higher, than in the works by other authors. We have confirmed a time-related reduction of anti-P450c21 AB levels, whereby the strength of the correlation was higher in the subgroups with autoimmune polyendocrine syndrome type II and, to a greater extent, autoimmune polyendocrine syndrome type I. This might be related to their different pathogenesis, with an abnormality of central immune tolerance in autoimmune polyendocrine syndrome type I and that of peripheral immune tolerance in autoimmune polyendocrine syndrome type II. According to our data, in 50% of cases, the development of AAI was preceded by the manifestation of other AIDs (in 15% of cases being multiple). Among all patients with no AAI diagnosis at the study entry, increased anti- P450c21 AB levels were found exactly in those with pre-existing AID. Thus, we have confirmed the feasibility of AAI screening primarily in a cohort of patients with other AID (especially multiple) belonging to the risk group.Conclusion: The determination of blood anti-P450c21 AB is a highly sensitive and highly specific method to diagnose AAI. The frequency of anti-P450c21 AB detection might depend on the duration of glucocorticoid treatment. Screening for early AAI stages is relevant primarily in the risk groups with multiple autoimmune disorders.

A novel cell-based assay for measuring neutralizing autoantibodies against type I interferons in patients with autoimmune polyendocrine syndrome type 1

2014 ◽  
Vol 153 (1) ◽  
pp. 220-227 ◽  
Author(s):  
Lars Breivik ◽  
Bergithe E.V. Oftedal ◽  
Anette S. Bøe Wolff ◽  
Eirik Bratland ◽  
Elizaveta M. Orlova ◽  
...  
Keyword(s):  
Type I Interferons ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Polyendocrine Syndrome

scholarly journals Characterization of the clinical and genetic spectrum of autoimmune polyendocrine syndrome type 1 in Chinese case series

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ya-Bing Wang ◽  
Ou Wang ◽  
Min Nie ◽  
Yan Jiang ◽  
Mei Li ◽  
...  
Keyword(s):  
Case Series ◽  
Pure Red Cell Aplasia ◽  
Hereditary Disease ◽  
Chinese Patients ◽  
Chronic Mucocutaneous Candidiasis ◽  
Syndrome Type ◽  
Myeloproliferative Disease ◽  
College Hospital ◽  
Autoimmune Polyendocrine Syndrome

Abstract Background Autoimmune polyendocrine syndrome type 1 (APS1) is a hereditary disease caused by mutations in the AIRE gene with both endocrine and non-endocrine organ involvement. The existing data from China are limited, and this study aims to describe the phenotypes and genetic characterization in Chinese APS1 patients. In this single-center, retrospective, observational study, comprehensive endocrine and extra-endocrine manifestations were collected, and genetic analysis in AIRE was conducted in patients with APS1 between the years of 1984 and 2018 at Peking Union Medical College Hospital. Results In total, 13 patients from 12 unrelated families were enrolled, seven of whom were female, with hypoparathyroidism, chronic mucocutaneous candidiasis, and Addison’s disease being the most frequently observed manifestations. Up to 84.7% presented with two or three of the above-mentioned manifestations, and nearly 4.9 ± 1.8 components presented in patients aged 21.2 ± 7.9 years old. Several less common phenotypes, such as myeloproliferative disease, pure red cell aplasia, renal tubular acidosis, asplenia, autoimmune hepatitis, and ankylosing spondylitis, were also observed in patients. Altogether, seven different AIRE mutations were found in six patients, four of which (K161fs, G208V, A246fs, and L308F) had not been previously reported in patients with APS1. Conclusion We have provided a comprehensive profile of Chinese patients with APS1, with less commonly observed features being observed in addition to more regularly seen manifestations. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1.

scholarly journals Acquired pure red cell aplasia and T cell large granular lymphocytic leukaemia in patients with autoimmune polyglandular syndrome type 1

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Ruan ◽  
Xuan Wang ◽  
Xianyong Jiang ◽  
Miao Chen
Keyword(s):  
Lymphocytic Leukaemia ◽  
Pure Red Cell Aplasia ◽  
Chronic Diarrhoea ◽  
Syndrome Type ◽  
Red Cell ◽  
Recurrent Pneumonia ◽  
Red Cell Aplasia ◽  
Autoimmune Polyendocrine Syndrome ◽  
Immunological Mechanisms

Abstract Background Pure red cell aplasia (PRCA) and large granular lymphocytic leukaemia (LGLL) are very rare complications of autoimmune polyendocrine syndrome type 1 (APS1). Here, we report a case of APS1 with PRCA and LGLL. Previous cases were reviewed, and possible mechanisms are discussed. Case presentation A 31-year-old female presented with anaemia and was diagnosed with PRCA in our centre. She also had hypoparathyroidism for 24 years, premature ovarian failure for 10 years, osteoporosis for 5 years, recurrent pneumonia with bronchiectasis for 4 years and chronic diarrhoea for 1 year. Boosted whole-exome analysis showed AIRE heterozygous mutations, confirming the diagnosis as APS1. LGLL was diagnosed during follow-up. The PRCA responded well to glucocorticoid. treatment Conclusion AIRE is causally related to the development of LGLL and consequent PRCA, which may be due to some immunological mechanisms.

scholarly journals Patients with autoimmune polyendocrine syndrome type 1 have an increased susceptibility to severe herpesvirus infections

2021 ◽  
Vol 231 ◽  
pp. 108851
Author(s):  
Iivo Hetemäki ◽  
Saila Laakso ◽  
Hannamari Välimaa ◽  
Iivari Kleino ◽  
Eliisa Kekäläinen ◽  
...  
Keyword(s):  
Syndrome Type ◽  
Autoimmune Polyendocrine Syndrome ◽  
Increased Susceptibility

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.

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