1,010 results match your criteria Candidiasis Chronic Mucocutaneous


STAT1 Gain-of-Function with Refractory Hemophagocytic Lymphohistiocytosis.

Ann Allergy Asthma Immunol 2020 Jul 3. Epub 2020 Jul 3.

Kaiser Permanente Los Angeles Medical Center.

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http://dx.doi.org/10.1016/j.anai.2020.06.042DOI Listing

A novel variant in AIRE causing a rare, non‑classical autoimmune polyendocrine syndrome type 1.

Mol Med Rep 2020 Jun 12. Epub 2020 Jun 12.

Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

Autoimmune polyendocrine syndrome type 1 (APS‑1) is a rare inherited autoimmune disease, characterized by a classic triad, including chronic mucocutaneous candidiasis, primary adrenocortical insufficiency and hypoparathyroidism. The present study investigated phenotypes and pathogenic variants in a Chinese woman with non‑classical APS‑1. Disease‑associated variants in a patient with APS‑1 were identified via targeted next generation sequencing and the variant was confirmed via Sanger sequencing. Read More

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http://dx.doi.org/10.3892/mmr.2020.11227DOI Listing

An IL-17F.S65L Knock-In Mouse Reveals Similarities and Differences in IL-17F Function in Oral Candidiasis: A New Tool to Understand IL-17F.

J Immunol 2020 Jun 29. Epub 2020 Jun 29.

Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261;

Oropharyngeal candidiasis (OPC) is an opportunistic infection of the oral mucosa caused by the commensal fungus IL-17R signaling is essential to prevent OPC in mice and humans, but the individual roles of its ligands, IL-17A, IL-17F, and IL-17AF, are less clear. A homozygous IL-17F deficiency in mice does not cause OPC susceptibility, whereas mice lacking IL-17A are moderately susceptible. In humans, a rare heterozygous mutation in IL-17F (IL-17F. Read More

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http://dx.doi.org/10.4049/jimmunol.2000394DOI Listing

Live Cell Imaging Demonstrates Multiple Routes Toward a STAT1 Gain-of-Function Phenotype.

Front Immunol 2020 9;11:1114. Epub 2020 Jun 9.

Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium.

Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations result in a primary immunodeficiency (PID) characterized typically by chronic mucocutaneous candidiasis (CMC), but a wider phenotypic range is reported and remains unexplained from a pathophysiological point-of-view. We hypothesized that different STAT1 GOF mutations may result in distinct molecular mechanisms, possibly explaining the variable phenotypes observed in patients. We selected STAT1 GOF mutants (R274W, R321S, T419R, and N574I) that are spread over the protein and studied their dynamic behavior in U3A and HeLa cell lines. Read More

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http://dx.doi.org/10.3389/fimmu.2020.01114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296103PMC

APECED-Associated Hepatitis: Clinical, Biochemical, Histological and Treatment Data from a Large Predominantly American Cohort.

Hepatology 2020 Jun 17. Epub 2020 Jun 17.

Translational Hepatology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Maryland, USA.

Background & Aims: Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), caused by autoimmune regulator (AIRE) mutations, manifests with chronic mucocutaneous candidiasis (CMC) and multisystem autoimmunity, most often hypoparathyroidism (HP) and adrenal insufficiency (AI). European cohorts previously reported a ~10% prevalence of APECED-associated hepatitis (APAH) with presentations ranging from asymptomatic laboratory derangements to fatal fulminant hepatic failure. Herein, we characterized APAH in a large APECED cohort from the Americas. Read More

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http://dx.doi.org/10.1002/hep.31421DOI Listing

Biological and clinical significance of T helper 17 cell deficiency: insight into monogenic defects.

Eur Ann Allergy Clin Immunol 2020 06 18. Epub 2020 Jun 18.

Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

T helper 17 (Th17) are a CD4+ T subpopulation cells which are involved in the host protection against microbes such as extracellular and intracellular bacteria, parasites, fungi, and viruses. Monogenic defects including those mutations in some genes such as the signal transducer and activator of transcription (STAT)1 and 3, dedicator of cytokinesis 8 (DOCK8), autoimmune regulator (AIRE), and interleukin 17 receptor A (IL-17RA) can lead to impairment in Th17 cell development and function along with the concomitant increased risk for chronic mucocutaneous candidiasis (CMC). The immunologic abnormalities in these patients include low frequency of Th17 cells; defective cutaneous or in vitro T cell response to Candida species, and/or autoantibodies against relevant cytokines. Read More

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http://dx.doi.org/10.23822/EurAnnACI.1764-1489.160DOI Listing

Recurrent, Severe Aphthous Stomatitis and Mucosal Ulcers as Primary Manifestations of a Novel Gain-of-Function Mutation.

Front Immunol 2020 28;11:967. Epub 2020 May 28.

Department of Infectious and Pediatric Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Chronic mucocutaneous candidiasis (CMC) characterized by persistent and recurrent Candida infection of the skin, nails, and the mucosa membranes has been proposed as the major infectious phenotype in patients with gain-of-function mutation of signal transducer and activator of transcription 1 (STAT1) 1. However, viral infections caused mostly by herpesviruses, and a broad range of autoimmune disorders may also be part of the clinical phenotype. We report here on a 31 years old female patient suffering from severe mucosal aphthous mucositis and ulcers and recurrent herpes simplex for decades. Read More

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http://dx.doi.org/10.3389/fimmu.2020.00967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270203PMC

Functional analysis of two STAT1 gain-of-function mutations in two Iranian families with autosomal dominant chronic mucocutaneous candidiasis.

Med Mycol 2020 Jun 11. Epub 2020 Jun 11.

Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Candidiasis is characterized by susceptibility to recurrent or persistent infections caused by Candida spp., typically Candida albicans, of cutaneous and mucosal surfaces. In this report, function and frequency of Th17 cells as well as genetics of patients susceptible to mucocutaneous candidiasis were studied. Read More

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http://dx.doi.org/10.1093/mmy/myaa043DOI Listing

An IL17RA frameshift variant in a Holstein cattle family with psoriasis-like skin alterations and immunodeficiency.

BMC Genet 2020 May 24;21(1):55. Epub 2020 May 24.

Institute of Animal Breeding and Genetics, Faculty of Agricultural Sciences, Nutritional Sciences and Environmental Management, Justus-Liebig University Giessen, 35390, Giessen, Germany.

Background: Skin lesions and dermatoses in cattle are often associated with infections due to bacteria, fungi or environmental risk factors. Dermatoses with genetic etiology have been described in cattle. Among these rare disorders, there are primary congenital dermatoses that are associated with inherited nutritional deficiencies, such as bovine hereditary zinc deficiency or zinc deficiency-like syndrome. Read More

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http://dx.doi.org/10.1186/s12863-020-00860-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247147PMC

Chronic mucocutaneous candidiasis: a rare diagnosis in paediatric dentistry.

Br J Oral Maxillofac Surg 2020 Apr 26. Epub 2020 Apr 26.

Department of Oral Medicine, Dental Institute, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Chronic mucocutaneous candidiasis is a rare disorder that is characterised by chronic or recurrent superficial candida infection of skin, nails, and mucous membranes. We describe such a case in a young boy who failed to respond to conventional therapy. It highlights the important role of the dental team in assessment, treatment, and onwards referral. Read More

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http://dx.doi.org/10.1016/j.bjoms.2020.03.025DOI Listing

Autosomal dominant hyper IgE syndrome from a single centre in Chongqing, China (2009-2018).

Scand J Immunol 2020 Jun 23;91(6):e12885. Epub 2020 Apr 23.

Clinical Immunology Laboratory, Pediatric Research Institute, Chongqing Key Laboratory of Child Infection and Immunity, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R China.

Autosomal dominant hyper IgE syndrome (AD-HIES) caused by STAT3 gene mutation is a rare primary immunodeficiency disease. To better understand the disease, we described the clinical characteristics of 20 AD-HIES patients in Chongqing, China and explored the effect of mutations in different domains of STAT3 gene on the function of STAT3 protein by Western blot and confocal microscopy. The mean age at onset was 0. Read More

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http://dx.doi.org/10.1111/sji.12885DOI Listing

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome.

J Exp Med 2020 Jun;217(6)

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. Read More

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http://dx.doi.org/10.1084/jem.20191804DOI Listing
June 2020
12.515 Impact Factor

Ruxolitinib treatment of a patient with steroid-dependent severe autoimmunity due to STAT1 gain-of-function mutation.

Int J Hematol 2020 Mar 16. Epub 2020 Mar 16.

Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.

Signal transducer and activator of transcription 1 gain-of-function (STAT1 GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC). We report the effect of oral ruxolitinib, an inhibitor of Janus kinase (JAK) family tyrosine kinases, on the clinical and immune status of a 3-year-old male with steroid-dependent severe autoimmunity due to a STAT1 GOF T385M mutation. The patient's susceptibility to infection improved with antimicrobial prophylaxis and immunoglobulin replacement therapy, but he continued to exhibit severely disabling symptoms of autoimmunity. Read More

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http://dx.doi.org/10.1007/s12185-020-02860-7DOI Listing

Persistence of Clonal Azole-Resistant Isolates of from a Patient with Chronic Mucocutaneous Candidiasis in Colombia.

J Glob Infect Dis 2020 Jan-Mar;12(1):16-20. Epub 2020 Feb 19.

Unidad de Proteómica y Micosis Humanas, Grupo de Enfermedades Infecciosas Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.

Purpose: The present article describes retrospectively a case of a patient with chronic mucocutaneous candidiasis (CMC) who presented recurrent infection since he was 6 months old. We obtained 16 isolates recovered during a 4-year period. Our purpose was to determinate the susceptibility, genotyping, and the pathogenicity profile in all the isolates. Read More

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http://dx.doi.org/10.4103/jgid.jgid_74_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045761PMC
February 2020

Human inborn errors of immunity underlying superficial or invasive candidiasis.

Authors:
Anne Puel

Hum Genet 2020 Jun 2;139(6-7):1011-1022. Epub 2020 Mar 2.

Laboratory of Human Genetics of Infectious Diseases, INSERM U1163, Necker Hospital for Sick Children, Necker Branch, 75015, Paris, France.

Candida species, including C. albicans in particular, can cause superficial or invasive disease, often in patients with known acquired immunodeficiencies or iatrogenic conditions. The molecular and cellular basis of these infections in patients with such risk factors remained largely elusive, until the study of inborn errors of immunity clarified the basis of the corresponding inherited and "idiopathic" infections. Read More

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http://dx.doi.org/10.1007/s00439-020-02141-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275885PMC

Molecular mechanism of azoles resistant Candida albicans in a patient with chronic mucocutaneous candidiasis.

BMC Infect Dis 2020 Feb 11;20(1):126. Epub 2020 Feb 11.

Department of Dermatology, the Second Hospital of Jilin University, No. 218, Ziqiang street, Nanguan district, Changchun, 130000, China.

Background: More and more azole-resistant strains emerged through the development of acquired resistance and an epidemiological shift towards inherently less susceptible species. The mechanisms of azoles resistance of Candida albicans is very complicated. In this study, we aim to investigate the mechanism of azole-resistant C. Read More

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http://dx.doi.org/10.1186/s12879-020-4856-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014776PMC
February 2020

Human STAT1 gain-of-function iPSC line from a patient suffering from chronic mucocutaneous candidiasis.

Stem Cell Res 2020 03 17;43:101713. Epub 2020 Jan 17.

JRG Translational Hematology of Congenital Diseases, Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany. Electronic address:

Chronic mucocutaneous candidiasis (CMC) is a disease that is characterized by susceptibility to chronic or recurrent infections with Candida spp. due to mutations affecting mainly the IL-17 signaling of T-Cells. The most common etiologies of CMC are gain-of-function (GOF) mutations in the STAT1 gene. Read More

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http://dx.doi.org/10.1016/j.scr.2020.101713DOI Listing

A novel compound heterozygous mutation of the AIRE gene in a patient with autoimmune polyendocrine syndrome type 1.

Ann Pediatr Endocrinol Metab 2019 Dec 31;24(4):248-252. Epub 2019 Dec 31.

Department of Pediatrics, Severance Children's Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Autoimmune polyendocrine syndrome type 1 (APS-1), or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare, autosomal recessive autoimmune disease caused by a mutation of the autoimmune regulator (AIRE) gene. The main symptom triad in APS-1 comprises chronic mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. Various autoimmune diseases and ectodermal abnormalities are also commonly associated with the syndrome. Read More

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http://dx.doi.org/10.6065/apem.2019.24.4.248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944864PMC
December 2019

Human gain-of-function STAT1 mutation disturbs IL-17 immunity in mice.

Int Immunol 2020 04;32(4):259-272

Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

Gain-of-function (GOF) mutations in the gene for signal transducer and activator of transcription 1 (STAT1) account for approximately one-half of patients with chronic mucocutaneous candidiasis (CMC) disease. Patients with GOF-STAT1 mutations display a broad variety of infectious and autoimmune manifestations in addition to CMC, and those with severe infections and/or autoimmunity have a poor prognosis. The establishment of safe and effective treatments based on a precise understanding of the molecular mechanisms of this disorder is required to improve patient care. Read More

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http://dx.doi.org/10.1093/intimm/dxz079DOI Listing

Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β.

Sci Immunol 2019 11;4(41)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.

Genetic etiologies of chronic mucocutaneous candidiasis (CMC) disrupt human IL-17A/F-dependent immunity at mucosal surfaces, whereas those of connective tissue disorders (CTDs) often impair the TGF-β-dependent homeostasis of connective tissues. The signaling pathways involved are incompletely understood. We report a three-generation family with an autosomal dominant (AD) combination of CMC and a previously undescribed form of CTD that clinically overlaps with Ehlers-Danlos syndrome (EDS). Read More

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http://dx.doi.org/10.1126/sciimmunol.aax7965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014825PMC
November 2019

A 7-Year-Old Child With Headaches and Prolonged Fever Associated With Oral and Nail Lesions.

Open Forum Infect Dis 2019 Nov 3;6(11):ofz229. Epub 2019 Nov 3.

Pediatric Infectious Diseases, General Pediatrics, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium.

A 7-year-old child of Turkish origin presented with headache and vomiting in the context of prolonged fever of unknown source. At examination, oral candidiasis and chronic onychomycosis were noted. A meningoencephalitis was diagnosed and intravenous Amphotericin B liposomal was given during 6 months relayed by oral Fluconazole after regression of CNS lesions was observed on MRI. Read More

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http://dx.doi.org/10.1093/ofid/ofz229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825800PMC
November 2019

[Chronic mucocutaneous candidiasis with STAT1 gain-of-function mutation associated with herpes virus and mycobacterial infections].

Ann Dermatol Venereol 2020 Jan 31;147(1):41-45. Epub 2019 Oct 31.

Laboratoire d'immunologie clinique, inflammation et allergie, faculté de médecine et de pharmacie de Casablanca, Hassan II University of Casablanca, Maroc; Unité d'immunologie clinique, service de pédiatrie infectieuse, CHU Harrouchi, Casablanca, Maroc.

Introduction: Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to chronic or recurrent infections with yeasts of the genus Candida affecting the skin, nails and mucous membranes. We describe a Moroccan patient presenting CMC with heterozygous STAT1 gain-of-function (GOF) mutation.

Patients And Methods: A 5-year-old boy with no consanguinity presented recurrent episodes of oral thrush, chronic nail candidiasis and herpetic gingivostomatitis from the age of 8 months. Read More

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http://dx.doi.org/10.1016/j.annder.2019.09.597DOI Listing
January 2020

STAT1 gain-of-function and chronic demodicosis.

Pediatr Dermatol 2020 Jan 21;37(1):153-155. Epub 2019 Oct 21.

Department of Dermatology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.

Heterozygous STAT1 gain-of-function (GOF) mutations result in a combined form of immunodeficiency which is the most common genetic cause of chronic mucocutaneous candidiasis (CMC). We present a pedigree with a GOF mutation in STAT1, manifesting with chronic demodicosis in the form of a facial papulopustular eruption, blepharitis, and chalazion. So far, demodicosis has been described in only one family with STAT1-GOF mutation. Read More

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http://dx.doi.org/10.1111/pde.14011DOI Listing
January 2020
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Delay in the Diagnosis of APECED: A Case Report and Review of Literature from Iran.

Immunol Invest 2020 Apr 7;49(3):299-306. Epub 2019 Oct 7.

Clinical Tuberculosis and Epidemiology Research Centre, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is a rare monogenic autosomal recessive disorder caused by biallelic mutations in the (autoimmune regulator) gene. Patients with APECED present with heterogeneous endocrine and non-endocrine manifestations. In this study, we report an Iranian patient who presented with Addison disease, chronic mucocutaneous candidiasis, alopecia totalis, keratopathy and asplenia treated as an isolated endocrinopathy for 25 years. Read More

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http://dx.doi.org/10.1080/08820139.2019.1671451DOI Listing
April 2020
1 Read
1.903 Impact Factor

Novel mutation in AIRE gene with autoimmune polyendocrine syndrome type 1.

Immunobiology 2019 11 6;224(6):728-733. Epub 2019 Sep 6.

Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Purpose: Autoimmune polyendocrine type 1 (APS-1) is a complex inherited autosomal recessive disorder. Classically, it appears within the first decade of life followed by adrenocortical insufficiency, mucocutaneous candidiasis, Addison's disease, and hypoparathyroidism. The clinical phenotype of APS-1 varies depending upon mutations in the autoimmune regulator gene (AIRE) on chromosome 21q22. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01712985193016
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http://dx.doi.org/10.1016/j.imbio.2019.09.004DOI Listing
November 2019
3 Reads
3.044 Impact Factor

Novel Gain-of-Function Mutation in Stat1 Sumoylation Site Leads to CMC/CID Phenotype Responsive to Ruxolitinib.

J Clin Immunol 2019 11 11;39(8):776-785. Epub 2019 Sep 11.

Department of Paediatric Immunology and Infectious Diseases, Children's Health Ireland, Crumlin, Dublin, D12 N512, Ireland.

Mutations in the coiled-coil and DNA-binding domains of STAT1 lead to delayed STAT1 dephosphorylation and subsequently gain-of-function. The associated clinical phenotype is broad and can include chronic mucocutaneous candidiasis (CMC) and/or combined immunodeficiency (CID). We report a case of CMC/CID in a 10-year-old boy due to a novel mutation in the small ubiquitin molecule (SUMO) consensus site at the C-terminal region of STAT1 leading to gain-of-function by impaired sumoylation. Read More

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http://dx.doi.org/10.1007/s10875-019-00687-4DOI Listing
November 2019
2 Reads

The activating p.Ser466Arg change in STAT1 causes a peculiar phenotype with features of interferonopathies.

Clin Genet 2019 12 4;96(6):585-589. Epub 2019 Sep 4.

Dipartimento Pediatrie Specialistiche, U. O. Reumatologia, Ospedale Pediatrico Bambino Gesù, Rome, Italy.

Signal Transducer and Activator of Transcription 1 (STAT1) is a DNA-binding signal transducer that regulates transcription of specific genes in response to IFNγ and IFNα/β stimulation. Loss-of-function mutations impairing STAT1 activity are known to confer susceptibility to intracellular bacterial and viral diseases. Conversely, the few known activating mutations of STAT1 allow predisposition to chronic mucocutaneous candidiasis disease, and occur in patients with combined immunodeficiency and defective Th1 and Th17 responses. Read More

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http://dx.doi.org/10.1111/cge.13632DOI Listing
December 2019
1 Read

Autoimmune Polyglandular Syndrome Type 1: a case report.

BMC Med Genet 2019 08 16;20(1):143. Epub 2019 Aug 16.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Mutations of the autoimmune regulator gene (AIRE), located on chromosome 21q22.3, are recognized as the cause of a rare monogenic organ-specific autoimmune disorder called autoimmune polyglandular syndrome type 1 (APS-1). Three major components of this syndrome include chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenocortical failure. Read More

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http://dx.doi.org/10.1186/s12881-019-0870-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698041PMC
August 2019
2 Reads

Identification of a distinct subset of disease-associated gain-of-function missense mutations in the STAT1 coiled-coil domain as system mutants.

Mol Immunol 2019 10 20;114:30-40. Epub 2019 Jul 20.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. Electronic address:

Heterozygous gain-of-function (GOF) mutations in the cytokine-regulated transcription factor STAT1 (signal transducer and activator of transcription 1) lead to chronic mucocutaneous candidiasis (CMC). However, the molecular basis of these pathogenic missense mutations is largely unknown. In this study, we characterized in more detail the CMC-associated GOF substitution mutation of arginine-to-tryptophan at position 274 (R274W) and, in addition, the adjacent glutamine-to-alanine mutation at position 275 (Q275A). Read More

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http://dx.doi.org/10.1016/j.molimm.2019.07.008DOI Listing
October 2019
3 Reads

Cachexia, Colitis, and Cancer.

Gastroenterology 2020 02 16;158(3):488-490. Epub 2019 Jul 16.

Department of Pathology, University of Michigan, Ann Arbor, Michigan.

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http://dx.doi.org/10.1053/j.gastro.2019.07.021DOI Listing
February 2020
8 Reads

A Human STAT1 Gain-of-Function Mutation Impairs CD8 T Cell Responses against Gammaherpesvirus 68.

J Virol 2019 10 12;93(19). Epub 2019 Sep 12.

Departments of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA

Autosomal dominant STAT1 mutations in humans have been associated with chronic mucocutaneous candidiasis (CMC), as well as with increased susceptibility to herpesvirus infections. Prior studies have focused on mucosal and Th17-mediated immunity against , but mechanisms of impaired antiviral immunity have not previously been examined. To begin to explore the mechanisms of STAT1-associated immunodeficiency against herpesviruses, we generated heterozygous STAT1 R274W knock-in mice that have a frequently reported STAT1 mutation associated in humans with susceptibility to herpesvirus infections. Read More

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http://jvi.asm.org/lookup/doi/10.1128/JVI.00307-19
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http://dx.doi.org/10.1128/JVI.00307-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744239PMC
October 2019
2 Reads

Chronic Mucocutaneous Candidiasis in an Adolescent Boy Due to a Novel Mutation in TRAF3IP2.

J Clin Immunol 2019 08 10;39(6):596-599. Epub 2019 Jul 10.

Strand Life Sciences, Bangalore, India.

Background: IL-17-mediated signaling is crucial in defense against fungi and bacteria. Defective Th17 immunity has been implicated in a group of disorders called chronic mucocutaneous candidiasis (CMC). TRAF3IP2 is an adaptor protein involved in downstream signaling for IL-17 receptors. Read More

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http://dx.doi.org/10.1007/s10875-019-00664-xDOI Listing
August 2019
10 Reads

Successful Allogenic Stem Cell Transplantation in Patients with Inherited CARD9 Deficiency.

J Clin Immunol 2019 07 20;39(5):462-469. Epub 2019 Jun 20.

Clinical Immunology, Faculdade de Medicina ABC, Av Lauro Gomes 2000, Santo Andre, Sao Paulo, 09060-870, Brazil.

Autosomal recessive (AR) CARD9 (caspase recruitment domain-containing protein 9) deficiency underlies invasive infections by fungi of the ascomycete phylum in previously healthy individuals at almost any age. Although CARD9 is expressed mostly by myeloid cells, the cellular basis of fungal infections in patients with inherited CARD9 deficiency is unclear. Therapy for fungal infections is challenging, with at least 20% premature mortality. Read More

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http://dx.doi.org/10.1007/s10875-019-00662-zDOI Listing
July 2019
11 Reads

Hematopoietic Stem Cell Transplantation in CARD9 Deficiency: Knight in Shining Armor?

Authors:
Isabelle Meyts

J Clin Immunol 2019 07 19;39(5):459-461. Epub 2019 Jun 19.

UZ Leuven, Department of Pediatrics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium.

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http://dx.doi.org/10.1007/s10875-019-00660-1DOI Listing
July 2019
9 Reads

Impaired STAT3-Dependent Upregulation of IL2Rα in B Cells of a Patient With a STAT1 Gain-of-Function Mutation.

Front Immunol 2019 24;10:768. Epub 2019 Apr 24.

The Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies in Melbourne, Melbourne, VIC, Australia.

Heterozygous gain-of-function (GOF) mutations form the most common genetic cause of chronic mucocutaneous candidiasis (CMC). In such patients, increased STAT1 function leads to impaired STAT3-dependent activation of IL-17A and IL-17F in T cells, thereby causing impaired Th17 responses to . In spite of the critical role of STAT3 in IL-21 signaling in B cells, nearly all STAT1 GOF patients have normal or high serum IgG. Read More

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http://dx.doi.org/10.3389/fimmu.2019.00768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491679PMC
April 2019
10 Reads

The Skin as a Window into Primary Immune Deficiency Diseases: Atopic Dermatitis and Chronic Mucocutaneous Candidiasis.

J Allergy Clin Immunol Pract 2019 03;7(3):788-798

Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY.

Primary immune deficiency diseases characteristically present with recurrent, severe, or unusual infections. These infections may often involve the skin, with mucocutaneous candidal infections seen in a variety of different primary immune deficiencies. Primary immune deficiencies may also present with noninfectious cutaneous complications, of which eczema is the most common. Read More

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http://dx.doi.org/10.1016/j.jaip.2018.11.026DOI Listing
March 2019
6 Reads

Interferon signature in patients with STAT1 gain-of-function mutation is epigenetically determined.

Eur J Immunol 2019 05 7;49(5):790-800. Epub 2019 Mar 7.

Department of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.

STAT1 gain-of-function (GOF) variants lead to defective Th17 cell development and chronic mucocutaneous candidiasis (CMC), but frequently also to autoimmunity. Stimulation of cells with STAT1 inducing cytokines like interferons (IFN) result in hyperphosphorylation and delayed dephosphorylation of GOF STAT1. However, the mechanism how the delayed dephosphorylation exactly causes the increased expression of STAT1-dependent genes, and how the intracellular signal transduction from cytokine receptors is affected, remains unknown. Read More

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http://dx.doi.org/10.1002/eji.201847955DOI Listing
May 2019
21 Reads

Molecular, Immunological, and Clinical Features of 16 Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease.

J Clin Immunol 2019 04 4;39(3):287-297. Epub 2019 Feb 4.

Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, 4th Floor, Building no.3, Children's Medical Center, Gharib St, Keshavarz Blvd, 14185-863, Tehran, IR, 14194, Iran.

Purpose: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency, triggered by non-tuberculous mycobacteria or Bacillus Calmette-Guérin (BCG) vaccines and characterized by severe diseases. All known genetic etiologies are inborn errors of IFN-γ-mediated immunity. Here, we report the molecular, cellular, and clinical features of patients from 15 Iranian families with disseminated disease without vaccination (2 patients) or following live BCG vaccination (14 patients). Read More

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http://link.springer.com/10.1007/s10875-019-0593-4
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http://dx.doi.org/10.1007/s10875-019-0593-4DOI Listing
April 2019
41 Reads

IRF and STAT Transcription Factors - From Basic Biology to Roles in Infection, Protective Immunity, and Primary Immunodeficiencies.

Authors:
Trine H Mogensen

Front Immunol 2018 8;9:3047. Epub 2019 Jan 8.

Department of Infectious diseases, Aarhus University Hospital, Aarhus, Denmark.

The induction and action of type I interferon (IFN) is of fundamental importance in human immune defenses toward microbial pathogens, particularly viruses. Basic discoveries within the molecular and cellular signaling pathways regulating type I IFN induction and downstream actions have shown the essential role of the IFN regulatory factor (IRF) and the signal transducer and activator of transcription (STAT) families, respectively. However, the exact biological and immunological functions of these factors have been most clearly revealed through the study of inborn errors of immunity and the resultant infectious phenotypes in humans. Read More

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http://dx.doi.org/10.3389/fimmu.2018.03047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331453PMC
October 2019
8 Reads

Immunologic characterization of patients with chronic mucocutaneous candidiasis disease.

Clin Case Rep 2019 Jan 4;7(1):180-185. Epub 2018 Dec 4.

Department of Internal Medicine, Division of Allergy/Immunology Albany Medical College Albany New York.

Even if initial immunologic screen is normal, a high index of suspicion for immunodeficiency should guide the evaluation and management of patients with recurrent episodes of mucocutaneous candidiasis. Although rare, a diagnosis of chronic mucocutaneous disease should always be considered in order to improve their outcome. Read More

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http://doi.wiley.com/10.1002/ccr3.1946
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http://dx.doi.org/10.1002/ccr3.1946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333065PMC
January 2019
33 Reads

Oral Administration of Human Polyvalent IgG by Mouthwash as an Adjunctive Treatment of Chronic Oral Candidiasis.

Front Immunol 2018 21;9:2956. Epub 2018 Dec 21.

Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.

is a commensal fungus that can cause disease ranging in severity from moderate to severe mucosal infections to more serious life-threating disseminated infections in severely immunocompromised hosts. Chronic mucocutaneous candidiasis (CMC) occurs in patients with mutations in genes affecting IL-17-mediated immunity, such as , and , or gain of function (GOF) mutations in . New strategies for the treatment of candidiasis are needed because of the increased burden of infections and the emergence of drug-resistant strains. Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2018.02956
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http://dx.doi.org/10.3389/fimmu.2018.02956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309162PMC
October 2019
34 Reads

STAT1 gain-of-function compromises skin host defense in the context of IFN-γ signaling.

J Allergy Clin Immunol 2019 04 18;143(4):1626-1629.e5. Epub 2018 Dec 18.

Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases, Nijmegen, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2018.11.033DOI Listing
April 2019
2 Reads

Hematopoietic Stem Cell Transplantation in Patients with Heterozygous STAT1 Gain-of-Function Mutation.

J Clin Immunol 2019 01 13;39(1):37-44. Epub 2018 Dec 13.

Division of Pediatric Allergy/Immunology, Marmara University, Fevzi Çakmak Mah. No: 41, Pendik, Istanbul, Turkey.

Purpose: Human signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations present with a broad range of manifestations ranging from chronic mucocutaneous candidiasis and autoimmunity to combined immunodeficiency (CID). So far, there is very limited experience with hematopoietic stem cell transplantation (HSCT) as a therapeutic modality in this disorder. Here, we describe two patients with heterozygous STAT1 GOF mutations mimicking CID who were treated with HSCT. Read More

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http://link.springer.com/10.1007/s10875-018-0575-y
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http://dx.doi.org/10.1007/s10875-018-0575-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430975PMC
January 2019
8 Reads

Chronic Mucocutaneous Candidiasis in Autoimmune Polyendocrine Syndrome Type 1.

Front Immunol 2018 19;9:2570. Epub 2018 Nov 19.

Department Parasitology-Mycology, CHU, Lille, France.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene, characterized by the clinical triad of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency. CMC can be complicated by systemic candidiasis or oral squamous cell carcinoma (SCC), and may lead to death. The role of chronic infection in the etiopathogenesis of oral SCC is unclear. Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2018.02570
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http://dx.doi.org/10.3389/fimmu.2018.02570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254185PMC
October 2019
32 Reads

Dysregulatory syndromes: the role of signal transducers and activators of transcription.

Curr Opin Pediatr 2018 12;30(6):821-828

Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP) CONICET- Inmunología, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina.

Purpose Of Review: A comparative description of dysregulatory syndromes with mutations in signal transducer and activator of transcription (STAT) genes.

Recent Findings: STAT 1, 3 and 5b loss of function (LOF) and gain of function (GOF) mutations are a heterogeneous group of genetic disorders that range from immunodeficiency (ID) to autoimmune disease (AID), depending on the underlying signalling pathway defect. Between them, there are clear overlapping and differences in clinical presentation and laboratory findings. Read More

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http://dx.doi.org/10.1097/MOP.0000000000000685DOI Listing
December 2018
4 Reads

Novel STAT1 Gain-of-Function Mutation Presenting as Combined Immunodeficiency.

J Clin Immunol 2018 10 13;38(7):753-756. Epub 2018 Oct 13.

Department of Pediatrics, Baylor College of Medicine, 1102 Bates, Suite 330, Houston, TX, 77030, USA.

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http://link.springer.com/10.1007/s10875-018-0554-3
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http://dx.doi.org/10.1007/s10875-018-0554-3DOI Listing
October 2018
38 Reads

Eosinophilia and reduced STAT3 signaling affect neutrophil cell death in autosomal-dominant Hyper-IgE syndrome.

Eur J Immunol 2018 12 29;48(12):1975-1988. Epub 2018 Oct 29.

Department of Clinical Microbiology, Karolinska University Hospital, Solna, Sweden.

The autosomal-dominant hyper-IgE syndrome (HIES), caused by mutations in STAT3, is a rare primary immunodeficiency that predisposes to mucocutaneous candidiasis and staphylococcal skin and lung infections. This infection phenotype is suggestive of defects in neutrophils, but data on neutrophil functions in HIES are inconsistent. This study was undertaken to functionally characterize neutrophils in STAT3-deficient HIES patients and to analyze whether the patients` eosinophilia affects the neutrophil phenotype in S. Read More

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http://dx.doi.org/10.1002/eji.201847650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587726PMC
December 2018
33 Reads

The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features, new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary care centers.

Clin Immunol 2018 12 1;197:231-238. Epub 2018 Oct 1.

Division of Endocrinology, Department of Medicine, Universidade Federal de Sao Paulo, Sao Paulo, Sao Paulo, Brazil.

Autoimmune polyendocrine syndrome type 1 (APS1) is characterized by multiorgan autoimmunity. We aim at characterizing a multi-center Brazilian cohort of APS1 patients by clinical evaluation, searching mutation in the AIRE gene, measuring serum autoantibodies, and investigating correlations between findings. We recruited patients based on the clinical criteria and tested them for AIRE mutations, antibodies against interferon type I and interleukins 17A, 17F and 22. Read More

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http://dx.doi.org/10.1016/j.clim.2018.09.012DOI Listing
December 2018
11 Reads