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Eystein S. Husebye - One of the best experts on this subject based on the ideXlab platform.
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Oral Tongue Malignancies in Autoimmune Polyendocrine Syndrome Type 1.
Frontiers in endocrinology, 2018Co-Authors: Øyvind Bruserud, Daniela Elena Costea, Saila Laakso, Ben-zion Garty, Eirik Mathisen, Antti Mäkitie, Outi Mäkitie, Eystein S. HusebyeAbstract:Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or Autoimmune Polyendocrine Syndrome type-1 (APS-1) (APECED, OMIM 240300) is a rare, childhood onset, monogenic disease caused by mutations in the Autoimmune Regulator (AIRE) gene. The overall mortality is increased compared to the general population and a major cause of death includes malignant diseases, especially oral and esophageal cancers. We here present a case series of four APS-1 patients with oral tongue cancers, an entity not described in detail previously. Scrutiny of history and clinical phenotypes indicate that chronic mucocutaneous candidiasis and smoking are significant risk factors. Preventive measures and early diagnosis are important to successfully manage this potentially fatal disease.
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Oral microbiota in Autoimmune Polyendocrine Syndrome type 1.
Journal of oral microbiology, 2018Co-Authors: Øyvind Bruserud, Eystein S. Husebye, Huma Siddiqui, Michaela Cuida Marthinussen, Tsute Chen, Roland Jonsson, Bergithe E. Oftedal, Ingar Olsen, Anette S. B. WolffAbstract:Background: Autoimmune Polyendocrine Syndrome type-1 (APS-1) is a rare, childhood onset disease caused by mutations in the Autoimmune Regulator gene. The phenotypic expression is highly variable an...
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Identification of endothelin-converting enzyme-2 as an autoantigen in Autoimmune Polyendocrine Syndrome type 1
Autoimmunity, 2017Co-Authors: Casey J. A. Smith-anttila, Mohammad Alimohammadi, Eystein S. Husebye, Sophie Bensing, Frida Dalin, Mikael Oscarson, Ming-dong Zhang, Jaakko Perheentupa, Jan Gustafsson, Peyman BjörklundAbstract:Autoimmune Polyendocrine Syndrome type 1 (APS1) is a rare monogenic Autoimmune disorder caused by mutations in the Autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic f...
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a novel cell based assay for measuring neutralizing autoantibodies against type i interferons in patients with Autoimmune Polyendocrine Syndrome type 1
Clinical Immunology, 2014Co-Authors: Lars Breivik, Bergithe E. Oftedal, Anette S. B. Wolff, Eirik Bratland, Elizaveta Orlova, Eystein S. HusebyeAbstract:An important characteristic of Autoimmune Polyendocrine Syndrome type 1 (APS 1) is the existence of neutralizing autoantibodies (nAbs) against the type I interferons (IFN) -α2 and -ω at frequencies close to 100%. Type 1 IFN autoantibodies are detected by antiviral neutralizing assays (AVA), binding assays with radiolabelled antigens (RLBA), enzyme-linked immunosorbent assay (ELISA), or by reporter-based cell assays. We here present a simple and reliable version of the latter utilizing a commercially available cell line (HEK-Blue IFN-α/β). All 67 APS 1 patients were positive for IFN-ω nAbs, while 90% were positive for IFN-α2 nAbs, a 100% and 96% correlation with RLBA, respectively. All blood donors and non-APS 1 patients were negative. The dilution titer required to reduce the effect of IFN-ω nAbs correlated with the RLBA index. This cell-based autoantibody assay (CBAA) is easy to perform, suitable for high throughput, while providing high specificity and sensitivity.
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Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients
The Journal of clinical endocrinology and metabolism, 2012Co-Authors: Antonella Meloni, Eystein S. Husebye, Anette S. B. Wolff, Nick Willcox, Anthony Meager, Michela Atzeni, Maria Furcas, Maria Cristina Rosatelli, Antonio Cao, Mauro CongiaAbstract:Context: Autoimmune Polyendocrine Syndrome type 1 (APS1) is a childhood-onset monogenic disorder caused by mutations in the Autoimmune regulator (AIRE) gene, including the distinctive R139X in Sardinia. Its rarity and great variability in manifestations/onset ages make early diagnosis difficult. To date, very few longitudinal studies of APS1 patients have been reported. Objective: The aim of this study was to describe the features and clinical course of APS1 and correlate them with AIRE and HLA class II genotypes in a large homogeneous cohort of Sardinian patients followed for up to 25 yr. Patients: Twenty-two pediatric APS1 patients were studied prospectively. Results: This Sardinian series (female/male ratio, 1.44; median current age, 30.7 yr; range, 1.8–46 yr) showed early disease onset (age range, 0.3–10 yr; median, 3.5 yr) and severe phenotype (on average, seven manifestations per patient). Besides the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease, auto...
Olle Kampe - One of the best experts on this subject based on the ideXlab platform.
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Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1.
The Journal of clinical endocrinology and metabolism, 2017Co-Authors: Elizaveta Orlova, Olle Kampe, Bergithe E. Oftedal, Anette S. B. Wolff, Leila S. Sozaeva, Maria Kareva, Lars Breivik, Ekaterina Y. Zakharova, O N Ivanova, Ivan Ivanovich DedovAbstract:Context Autoimmune Polyendocrine Syndrome type 1 (APS-1) is a rare monogenic Autoimmune disease caused by mutations in the Autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare. Objective To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort. Subjects and methods Clinical components were mapped by systematic investigations, sera were screened for autoantibodies associated with APS-1, and AIRE mutations were characterized by Sanger sequencing. Results We identified 112 patients with APS-1, which is, to the best of our knowledge, the largest cohort described to date. Careful phenotyping revealed several additional and uncommon phenotypes such as cerebellar ataxia with pseudotumor, ptosis, and retinitis pigmentosa. Neutralizing autoantibodies to interferon-ω were found in all patients except for one. The major Finnish mutation c.769C>T (p.R257*) was the most frequent and was present in 72% of the alleles. Altogether, 19 different mutations were found, of which 9 were unknown: c.38T>C (p.L13P), c.173C>T (p.A58V), c.280C>T (p.Q94*), c.554C>G (p.S185*), c.661A>T (p.K221*), c.821del (p.Gly274Afs*104), c.1195G>C (p.A399P), c.1302C>A (p.C434*), and c.1497del (p.A500Pfs*21). Conclusions The spectrum of phenotypes and AIRE mutation in APS-1 has been expanded. The Finnish major mutation is the most common mutation in Russia and is almost as common as in Finland. Assay of interferon antibodies is a robust screening tool for APS-1.
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Autoimmune Polyendocrine Syndrome type 1 in an Indian cohort: a longitudinal study.
Endocrine connections, 2017Co-Authors: Ghazala Zaidi, Sophie Bensing, Daniel Eriksson, Vijayalakshmi Bhatia, Saroj Kumar Sahoo, Aditya Narayan Sarangi, Niharika Bharti, Li Zhang, Olle KampeAbstract:OBJECTIVE Autoimmune Polyendocrine Syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and Autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients. DESIGN Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2-19) years. METHODS Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied. RESULTS Patients varied widely in their age of presentation [3.5 (0.1-17) years] and number of clinical manifestations [5 (2-11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and Autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3-23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians. CONCLUSIONS Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.
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Rapid Publication GAD Autoantibodies in IDDM, Stiff-Man Syndrome, and Autoimmune Polyendocrine Syndrome Type I Recognize Different Epitopes
2016Co-Authors: Elisabeth Bjork, Olle Kampe, Licio A. Velloso, Anders F. KarlssonAbstract:Glutamic acid decarboxylase (GAD) is a major islet cell autoantigen in insulin-dependent diabetes mellitus (IDDM), and autoantibodies are found in high frequencies in patients with recent-onset IDDM, stiff-man Syndrome (SMS), and Autoimmune Polyendocrine Syndrome type I (APS I). Antigens in Autoimmune disorders are often enzymes, and autoantibody binding frequently inhibit their activity. In this study, we examined the reactivity of anti-GAD-containing sera from 7 patients with IDDM, 4 patients with SMS, and 5 patients with APS I. All sera immunoprecipitated GAD from [35S]methionine-labeled rat islet lysates and the sera from patients with SMS and APS I, but none of the IDDM patients ' sera, identified the GAD protein in Western blots. Two o
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Identification of Autoimmune Polyendocrine Syndrome type 1 in patients with isolated hypoparathyroidism
Clinical endocrinology, 2016Co-Authors: Saroj Kumar Sahoo, Olle Kampe, Sophie Bensing, Daniel Eriksson, Ghazala Zaidi, Aditya Narayan Sarangi, Niharika Bharti, Rajni Srivastava, Amita Aggarwal, Rakesh AggarwalAbstract:SummaryObjective The prevalence of Autoimmune Polyendocrine Syndrome type 1 (APS1) among isolated hypoparathyroidism (HP) or primary adrenal insufficiency (PAI) is not well established. We studied the frequency of APS1 in patients with HP or PAI by measuring interferon-α (IFN-α) antibody levels, a highly sensitive and specific marker for APS1. Design, patients and measurements In a single-centre cross-sectional study, 37 Indian patients with isolated HP and 40 patients with PAI were tested for IFN-α antibody using an indirect ELISA. In patients with elevated IFN-α antibody, the Autoimmune regulator (AIRE) gene was bidirectionally sequenced. Results Three (8·1%) patients with isolated HP had elevated IFN-α antibody levels (range: 367–17382 units; positive titre >56 units). Homozygous or compound heterozygous AIRE mutations were detected in all three patients, including a novel mutation (p.T68P). All three APS1 patients had atypical features. The first patient, diagnosed at 7 years of age, died suddenly 5 months later. The second patient had late-onset HP (at the age of 34 years) and a solitary episode of transient mucocutaneous candidiasis 5 years later. The final patient developed HP at the age of 14 years and premature ovarian insufficiency 14 years later. Interleukin-22 antibodies, as well as most other organ-specific antibodies, were absent in the 3 APS1 patients. All patients with PAI were negative for IFN-α antibody. Conclusion Eight percentage of patients with isolated HP had elevated IFN-α antibody levels and AIRE mutation-positive APS1. All APS1 patients had atypical clinical features. Testing for IFN-α antibody should be considered in patients with idiopathic HP.
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Autoimmune Polyendocrine Syndrome Type I: Man
Immunoendocrinology: Scientific and Clinical Aspects, 2010Co-Authors: Eystein S. Husebye, Olle KampeAbstract:Autoimmune Polyendocrine Syndrome type I (APS-I) is a monogenic disease with the three main components: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. In addition, a number of other endocrine, gastrointestinal, and ectodermal tissues are targeted. There is a huge variability in clinical phenotype, but in typical cases main components appear in childhood and adolescence. The main diagnostic criterion is still the presence of two of the three main components, but diagnosis can be aided by the mutational analysis of the Autoimmune regulator (AIRE) gene and assay of specific autoantibodies, particularly against interferon omega and alpha. Many patients are diagnosed late or not at all, and the management is not optimal. An overview of the main clinical aspects, diagnostic approaches, and treatment will hopefully contribute to improved care for APS-I patients.
Corrado Betterle - One of the best experts on this subject based on the ideXlab platform.
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A rare combination of type 3 Autoimmune Polyendocrine Syndrome (APS-3) or multiple Autoimmune Syndrome (MAS-3)
Autoimmunity Highlights, 2014Co-Authors: Corrado Betterle, Silvia Garelli, Graziella Coco, Patrizia BurraAbstract:Context Type 3 Autoimmune Polyendocrine Syndrome (APS-3) is defined by the presence of an Autoimmune thyroid disease and another Autoimmune illness, excluding Addison’s disease; this is a frequent combination. Case presentation We report the case of a 55 years old female patient with APS-3, with seven clinical or latent Autoimmune manifestations. At 49 years of age she was admitted at the General Hospital for leukopenia, weight loss, tremors, anxiety and diarrhea. The personal history revealed ulcerative colitis and, during the last year, episodes of fever with migrant arthralgia and cutaneous lesions. The patient was evaluated for thyroid function and imaging, mielobiopsy, glycaemic control, gastrointestinal and rheumatologic disorders with specific biochemical tests, imaging and endoscopic procedures. We concluded that the patient was affected by APS-3, characterized by the association of Graves’ disease, Autoimmune leukopenia, latent Autoimmune diabetes of the adult (LADA), Autoimmune gastritis, ulcerative colitis, Sjögren’s and anti-phospholipid Syndromes. The patient started low doses of corticosteroid drugs for leukopenia, underwent ^131I therapy for hyperthyroidism and later started substitutive thyroid therapy with l -thyroxine, insulin therapy for LADA, mesalazine for ulcerative colitis and artificial tears for Sjögren’s Syndrome. Conclusions In this article we report a complex case of APS-3, characterized by the association of seven different Autoimmune diseases, which required a complex therapeutic strategy.
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A rare combination of type 3 Autoimmune Polyendocrine Syndrome (APS-3) or multiple Autoimmune Syndrome (MAS-3)
Auto- immunity highlights, 2014Co-Authors: Corrado Betterle, Silvia Garelli, Graziella Coco, Patrizia BurraAbstract:Context Type 3 Autoimmune Polyendocrine Syndrome (APS-3) is defined by the presence of an Autoimmune thyroid disease and another Autoimmune illness, excluding Addison’s disease; this is a frequent combination.
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Knowing it for detecting it: Addison disease with type 2 Autoimmune Polyendocrine Syndrome
Giornale di Tecniche Nefrologiche e Dialitiche, 2013Co-Authors: Marco Lombardi, Stefano Michelassi, Corrado BetterleAbstract:Here we describe a patient who developed Autoimmune hypoadrenalism many years after developing Graves’ disease. This combination depicts an Autoimmune Polyendocrine Syndrome type-2 (APS-2).APS-2 is...
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Autoimmunity and cystatin SA 1 deficiency behind chronic mucocutaneous candidiasis in Autoimmune Polyendocrine Syndrome
Journal of Translational Medicine, 2012Co-Authors: Emma Lindh, Corrado Betterle, Ben-zion Garty, Johan Brännström, Petra Jones, Fredrik Wermeling, Signe Hässler, Mats Stridsberg, Björn Herrmann, Mikael C. I. KarlssonAbstract:Patients with the monogenic disease Autoimmune Polyendocrine Syndrome type I (APS I) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report that saliva from APS I patients with CMC was defective in inhibiting growth of C. albicans in vitro and had reduced levels of a salivary protein identified as cystatin SA1. In contrast, APS I patients with no CMC expressed salivary cystatin SA1 and could inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibited growth of C. albicans in vitro. Moreover, APS I patients exhibited salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands that also produce cystatin SA1, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an Autoimmune mechanism behind CMC in APS I and provide rationale for evaluating cystatin SA1 in antifungal therapy.
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Autoimmunity and Cystatin SA1 Deficiency Behind Chronic Mucocutaneous Candidiasis in Autoimmune Polyendocrine Syndrome Type 1
Journal of autoimmunity, 2012Co-Authors: Emma Lindh, Corrado Betterle, Ben-zion Garty, Johan Brännström, Petra Jones, Fredrik Wermeling, Signe Hässler, Mats Stridsberg, Björn Herrmann, Mikael C. I. KarlssonAbstract:Patients with the monogenic disease Autoimmune Polyendocrine Syndrome type I (APSI) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report here that saliva from APSI patients with CMC is defective in inhibiting growth of Candida albicans in vitro and show reduced levels of a salivary protein identified as cystatin SA1. In contrast, APSI patients without CMC express salivary cystatin SA1 and can inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibits growth of C. albicans in vitro. Moreover, APSI patients exhibit salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an Autoimmune mechanism behind CMC in APSI and provides rationale for evaluating cystatin SA1 in antifungal therapy.
Jan Gustafsson - One of the best experts on this subject based on the ideXlab platform.
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Identification of endothelin-converting enzyme-2 as an autoantigen in Autoimmune Polyendocrine Syndrome type 1
Autoimmunity, 2017Co-Authors: Casey J. A. Smith-anttila, Mohammad Alimohammadi, Eystein S. Husebye, Sophie Bensing, Frida Dalin, Mikael Oscarson, Ming-dong Zhang, Jaakko Perheentupa, Jan Gustafsson, Peyman BjörklundAbstract:Autoimmune Polyendocrine Syndrome type 1 (APS1) is a rare monogenic Autoimmune disorder caused by mutations in the Autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic f...
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Proteome-wide survey of the Autoimmune target repertoire in Autoimmune Polyendocrine Syndrome type 1.
Scientific reports, 2016Co-Authors: Nils Landegren, Åsa Hallgren, Sophie Bensing, Donald Sharon, Eva Freyhult, Daniel Eriksson, Per-henrik Edqvist, Jeanette Wahlberg, Lawrence M. Nelson, Jan GustafssonAbstract:Autoimmune Polyendocrine Syndrome type 1 (APS1) is a monogenic disorder that features multiple Autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of Autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE’s selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.
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tsga10 a target for autoantibodies in Autoimmune Polyendocrine Syndrome type 1 and systemic lupus erythematosus
Scandinavian Journal of Immunology, 2011Co-Authors: Mohammad Alimohammadi, Eystein S. Husebye, Mikael Oscarson, Jan Gustafsson, J Perheentupa, Casey Smith, Lars Rönnblom, Gunnel Nordmark, Antonella MeloniAbstract:Autoimmune Polyendocrine Syndrome type 1 (APS1) is a rare monogenic Autoimmune disorder caused by mutations in the Autoimmune regulator (AIRE) gene. High-titre autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in approximately 7% of APS1 patients, with immunoreactivity to pituitary tissue frequently described. Using APS1 patient serum to immunoscreen a pituitary cDNA expression library, testis specific, 10 (TSGA10) was isolated. Immunoreactivity against TSGA10 was detected in 5/99 (5.05%) patients with APS1, but also in 5/135 (3.70%) systemic lupus erythematosus (SLE) patients and 1/188 (0.53%) healthy controls. TSGA10 autoantibodies were not detected in the serum from patients with any other Autoimmune disease. Autoantibodies against TSGA10 were detectable from a young age in 4/5 positive APS1 patients with autoantibody titres remaining relatively constant over time. Furthermore, real-time PCR confirmed TSGA10 mRNA to be most abundantly expressed in the testis and also showed moderate and low expression levels throughout the entire body. TSGA10 should be considered as an autoantigen in a subset of APS1 patients and also in a minority of SLE patients. No recognizable clinical phenotype could be found to correlate with positive autoantibody reactivity.
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TSGA10 – A Target for Autoantibodies in Autoimmune Polyendocrine Syndrome Type 1 and Systemic Lupus Erythematosus
Scandinavian journal of immunology, 2011Co-Authors: Casey Smith, Mohammad Alimohammadi, Eystein S. Husebye, Antonella Meloni, Mikael Oscarson, Jaakko Perheentupa, Jan Gustafsson, Lars Rönnblom, Gunnel Nordmark, Patricia CrockAbstract:Autoimmune Polyendocrine Syndrome type 1 (APS1) is a rare monogenic Autoimmune disorder caused by mutations in the Autoimmune regulator (AIRE) gene. High-titre autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in approximately 7% of APS1 patients, with immunoreactivity to pituitary tissue frequently described. Using APS1 patient serum to immunoscreen a pituitary cDNA expression library, testis specific, 10 (TSGA10) was isolated. Immunoreactivity against TSGA10 was detected in 5/99 (5.05%) patients with APS1, but also in 5/135 (3.70%) systemic lupus erythematosus (SLE) patients and 1/188 (0.53%) healthy controls. TSGA10 autoantibodies were not detected in the serum from patients with any other Autoimmune disease. Autoantibodies against TSGA10 were detectable from a young age in 4/5 positive APS1 patients with autoantibody titres remaining relatively constant over time. Furthermore, real-time PCR confirmed TSGA10 mRNA to be most abundantly expressed in the testis and also showed moderate and low expression levels throughout the entire body. TSGA10 should be considered as an autoantigen in a subset of APS1 patients and also in a minority of SLE patients. No recognizable clinical phenotype could be found to correlate with positive autoantibody reactivity.
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Increased IL‐17A secretion in response to Candida albicans in Autoimmune Polyendocrine Syndrome type 1 and its animal model
European journal of immunology, 2010Co-Authors: Kerstin M. Ahlgren, Åsa Hallgren, Jaakko Perheentupa, Jan Gustafsson, Silvia Moretti, Brita Ardesjö Lundgren, Iulia Karlsson, Erik Åhlin, Anna Norling, Fredrik RorsmanAbstract:Autoimmune Polyendocrine Syndrome type 1 (APS-1) is a multiorgan Autoimmune disease caused by mutations in the Autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.
Patrizia Burra - One of the best experts on this subject based on the ideXlab platform.
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A rare combination of type 3 Autoimmune Polyendocrine Syndrome (APS-3) or multiple Autoimmune Syndrome (MAS-3)
Autoimmunity Highlights, 2014Co-Authors: Corrado Betterle, Silvia Garelli, Graziella Coco, Patrizia BurraAbstract:Context Type 3 Autoimmune Polyendocrine Syndrome (APS-3) is defined by the presence of an Autoimmune thyroid disease and another Autoimmune illness, excluding Addison’s disease; this is a frequent combination. Case presentation We report the case of a 55 years old female patient with APS-3, with seven clinical or latent Autoimmune manifestations. At 49 years of age she was admitted at the General Hospital for leukopenia, weight loss, tremors, anxiety and diarrhea. The personal history revealed ulcerative colitis and, during the last year, episodes of fever with migrant arthralgia and cutaneous lesions. The patient was evaluated for thyroid function and imaging, mielobiopsy, glycaemic control, gastrointestinal and rheumatologic disorders with specific biochemical tests, imaging and endoscopic procedures. We concluded that the patient was affected by APS-3, characterized by the association of Graves’ disease, Autoimmune leukopenia, latent Autoimmune diabetes of the adult (LADA), Autoimmune gastritis, ulcerative colitis, Sjögren’s and anti-phospholipid Syndromes. The patient started low doses of corticosteroid drugs for leukopenia, underwent ^131I therapy for hyperthyroidism and later started substitutive thyroid therapy with l -thyroxine, insulin therapy for LADA, mesalazine for ulcerative colitis and artificial tears for Sjögren’s Syndrome. Conclusions In this article we report a complex case of APS-3, characterized by the association of seven different Autoimmune diseases, which required a complex therapeutic strategy.
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A rare combination of type 3 Autoimmune Polyendocrine Syndrome (APS-3) or multiple Autoimmune Syndrome (MAS-3)
Auto- immunity highlights, 2014Co-Authors: Corrado Betterle, Silvia Garelli, Graziella Coco, Patrizia BurraAbstract:Context Type 3 Autoimmune Polyendocrine Syndrome (APS-3) is defined by the presence of an Autoimmune thyroid disease and another Autoimmune illness, excluding Addison’s disease; this is a frequent combination.
