J Mycol Med 2018 Mar 28;28(1):206-210. Epub 2018 Feb 28.

Mycology Research Center, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

Chronic mucocutaneous candidiasis (CMC) is a clinically heterogeneous disease. Some immunologic and hormonal abnormalities have been associated with CMC. The factors that predispose host to CMC infection could be autosomal or acquisitive. Read More

Gene 2018 May 16;654:64-68. Epub 2018 Feb 16.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. Electronic address:

Recurrent Aphthous Stomatitis (RAS) is a common oral inflammatory disease with unknown pathogenesis. Although the immune system alterations could be involved in predisposition of individuals to oral candidiasis, precise etiologies of RAS have not been understood yet. A recent study showed that autosomal dominant IL17F deficiency could cause chronic mucocutaneous candidiasis. Read More

Cold Spring Harb Mol Case Stud 2018 Feb 1. Epub 2018 Feb 1.

Rady Children's Institute for Genomic Medicine.

Autoimmune polyendocrine syndrome type 1 (APS1; OMIM #240300), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare monogenic disorder caused by mutations in the autoimmune regulator (AIRE) gene. APS1 is classically characterized by a triad of chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and autoimmune adrenocortical insufficiency. We report a five-year-old female who presented with symptoms of tetany due to hypocalcemia and was subsequently found to be secondary to hypoparathyroidism. Read More

J Fungi (Basel) 2017 Sep 27;3(4). Epub 2017 Sep 27.

Department of Biological Sciences, The University of Toledo, 2801 West Bancroft St., Toledo, OH 43606, USA.

Interleukin-17 (IL-17) is a proinflammatory cytokine produced by adaptive CD4+ T helper cells and innate lymphocytes, such as γδ-T cells and TCRβ+ "natural" Th17 cells. IL-17 activates signaling through the IL-17 receptor, which induces other proinflammatory cytokines, antimicrobial peptides and neutrophil chemokines that are important for antifungal activity. The importance of IL-17 in protective antifungal immunity is evident in mice and humans, where various genetic defects related to the IL-17-signaling pathway render them highly susceptible to forms of candidiasis such oropharyngeal candidiasis (OPC) or more broadly chronic mucocutaneous candidiasis (CMC), both caused mainly by the opportunistic fungal pathogen . Read More

J Fungi (Basel) 2018 Jan 9;4(1). Epub 2018 Jan 9.

Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

spp. are colonizing fungi of human skin and mucosae of the gastrointestinal and genitourinary tract, present in 30-50% of healthy individuals in a population at any given moment. The host defense mechanisms prevent this commensal fungus from invading and causing disease. Read More

Front Immunol 2017 6;8:1651. Epub 2017 Dec 6.

Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, México.

In humans, recessive loss-of-function mutations in are associated with mycobacterial and viral infections, whereas gain-of-function (GOF) mutations in are associated with a type of primary immunodeficiency related mainly, but not exclusively, to chronic mucocutaneous candidiasis (CMC). We studied and established a molecular diagnosis in a pediatric patient with mycobacterial infections, associated with CMC. The patient, daughter of a non-consanguineous mestizo Mexican family, had axillary adenitis secondary to BCG vaccination and was cured with resection of the abscess at 1-year old. Read More

Case Reports Immunol 2017 13;2017:2846928. Epub 2017 Nov 13.

Ege University Medical Faculty, Department of Pediatric Immunology, Izmir, Turkey.

Chronic Mucocutaneous Candidiasis (CMC) is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. grew in oral mucosa swab. Read More

Open Forum Infect Dis 2017 22;4(4):ofx202. Epub 2017 Sep 22.

Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, Maryland.

Heterozygous gain-of-function (GOF) mutations are associated with chronic mucocutaneous candidiasis and a broad spectrum of infectious, inflammatory, and vascular manifestations. We describe therapeutic failures with the Janus Kinase (JAK) inhibitor ruxolitinib in 2 GOF patients with severe invasive or cutaneous fungal infections. Read More

Indian Dermatol Online J 2017 Nov-Dec;8(6):391-405

Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Primary immunodeficiency disorders (PIDs) are a group of disorders affecting the capability to fight against infection. These include defects in T cells and B cells affecting cell-mediated and humoral immunity, respectively, combined humoral and cell-mediated immunodeficiency, defects in phagocytosis, complement defects, and defects in cytokine or cytokine signalling pathways which are detrimental for immune function. Depending upon the type and severity, age at onset of symptoms can vary from neonatal period to late childhood. Read More

Transl Pediatr 2017 Oct;6(4):300-312

The Ohio State University College of Medicine, Columbus, OH, USA.

The skin serves as a window for clinicians to understand, diagnose, and monitor endocrine disease. Dermatologic manifestations of endocrinopathies contribute significantly to an individual's health and quality of life. In this review, we outline various disorders of the hypothalamic-pituitary axis, thyroid gland, pancreas, adrenal gland, and androgen axis as well as hereditary endocrine syndromes. Read More

Eur J Immunol 2018 Mar 11;48(3):464-470. Epub 2017 Dec 11.

Department of Molecular Pathology, Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia.

Protection against mucocutaneous candidiasis depends on the T helper (Th)17 pathway, as gene defects affecting its integrity result in inability to clear Candida albicans infection on body surfaces. Moreover, autoantibodies neutralizing Th17 cytokines have been related to chronic candidiasis in a rare inherited disorder called autoimmune polyendocriopathy candidiasis ectodermal dystrophy (APECED) caused by mutations in autoimmune regulator (AIRE) gene. However, the direct pathogenicity of these autoantibodies has not yet been addressed. Read More

Curr Opin Microbiol 2017 Dec 10;40:46-57. Epub 2017 Nov 10.

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, EU, France; Paris Descartes University, Imagine Institute, 75015 Paris, EU, France. Electronic address:

It has been estimated that there are at least 1.5 million fungal species, mostly present in the environment, but only a few of these fungi cause human disease. Most fungal diseases are self-healing and benign, but some are chronic or life-threatening. Read More

Autoimmun Rev 2018 Jan 4;17(1):78-85. Epub 2017 Nov 4.

Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Davis, CA 95616, USA. Electronic address:

Autoimmune Polyglandular Syndrome type 1 (APS-1) is a subtype of the autoimmune polyendocrine syndrome characterized by the simultaneous or sequential dysfunction of multiple endocrine or non-endocrine glands. A clinical diagnosis of APS-1 is typically based on the presence of at least two of three following criteria: chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. The first identified causative mutated gene for APS-1 is autoimmune regulator (AIRE) encoding a critical transcription factor, which is primarily expressed in the medullary thymic epithelial cells (mTECs) for generating central immune tolerance. Read More

J Dermatolog Treat 2017 Nov 21:1-6. Epub 2017 Nov 21.

a Department of Dermatology Wake Forest School of Medicine , Winston-Salem , NC , USA.

Purpose: IL-17 antagonists are effective for psoriasis in clinical trials, but long-term safety is not fully characterized. Since chronic mucocutaneous candidiasis (CMC) is caused by defects in the IL-17 pathway, CMC risk data have been touted as providing reassurance about the safety of IL-17 antagonism.

Methods: We performed a literature review to identify patients with CMC and compared the prevalence of cancer in these patients to the reported 5-year prevalence. Read More

Pediatrics 2017 Nov 12;140(5). Epub 2017 Oct 12.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute.

Tuberculosis is a major worldwide problem, and protection from it is achieved mainly by live attenuated bacille Calmette-Guérin vaccine, which is capable of causing disease in immunocompromised host. Oral thrush is abnormal in healthy children, which suggests an underlying immunodeficiency. Mendelian susceptibility to mycobacterial disease is a rare primary immunodeficiency characterized by a selective predisposition to weakly virulent and and also predisposition to chronic mucocutaneous candidiasis. Read More

Br J Neurosurg 2017 Oct 10:1-2. Epub 2017 Oct 10.

c Division of Neurological Surgery , University of Sao Paulo, School of Medicine , Sao Paulo , Brazil.

Some authors have reported the association between CMC and brain aneurysms. In this paper it is reported a fusiform brain aneurysm associated to CMC and the vessel wall MRI findings. Read More

J Allergy Clin Immunol Pract 2017 Sep 19. Epub 2017 Sep 19.

Division of Allergy and Clinical Immunology, Icahn School of Medicine, Mount Sinai, New York, NY. Electronic address:

Background: Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare condition.

Objective: Data from the USIDNET Registry provide a resource to examine the characteristics of patients with rare immune deficiency diseases.

Methods: A query was submitted to the USIDNET requesting deidentified data for patients with physician-diagnosed AD-HIES through July 2016. Read More

Front Immunol 2017 1;8:1074. Epub 2017 Sep 1.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Objective: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare, childhood onset disease caused by mutations in the () gene. Chronic mucocutaneous candidiasis (CMC) is one of the three major disease components and is, to date, mainly explained by the presence of neutralizing auto-antibodies against cytokines [interleukin (IL)-17A, IL-17F, and IL-22] from T helper 17 cells, which are critical for the protection against fungal infections. However, patients without current auto-antibodies also present CMC and we, therefore, hypothesized that other immune mechanisms contribute to CMC in APS-1. Read More

J Clin Endocrinol Metab 2017 Sep;102(9):3546-3556

Department of Clinical Science, University of Bergen, Bergen 5020, Norway.

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. Read More

Adv Biomed Res 2017 28;6:103. Epub 2017 Aug 28.

Department of Medical Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: species can become opportunistic pathogens causing local or systemic invasive infections. Gastroesophageal candidiasis may depend on the colonization and local damage of the mucosal barrier. Risk factors are gastric acid suppression, diabetes mellitus, chronic debilitating states such as carcinomas, and the use of systemic antibiotics and corticosteroids. Read More

Int J Fertil Steril 2017 Oct 27;11(3):134-141. Epub 2017 Aug 27.

Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Background: Recurrent vulvovaginal candidiasis (RVVC) is a common cause of morbidity affecting millions of women worldwide. Patients with RVVC are thought to have an underlying immunologic defect. This study has been established to evaluate cell-mediated immunity defect in response to candida antigen in RVVC cases. Read More

J Allergy Clin Immunol 2017 Aug 30. Epub 2017 Aug 30.

Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Background: Sumoylation is a posttranslational reversible modification of cellular proteins through the conjugation of small ubiquitin-related modifier (SUMO) and comprises an important regulator of protein function.

Objective: We sought to characterize the molecular mechanism of a novel mutation at the SUMO motif on signal transducer and activator of transcription 1 (STAT1).

Methods: STAT1 sequencing and functional characterization were performed in transfection experiments by using immunoblotting and immunoprecipitation in STAT1-deficient cell lines. Read More

United European Gastroenterol J 2017 Aug 6;5(5):625-631. Epub 2016 Dec 6.

Departments of Gastroenterology and Clinical Immunology, County Durham and Darlington NHS Foundation Trust, County Durham, UK.

Background: Oesophageal candidiasis is a common, usually self-limiting opportunistic infection, but long-term infection with is known to predispose to oral and oesophageal squamous cell cancer (SCC). Permissive factors that lead to immune deficiencies can underlie persistent or recurring candidiasis, called chronic mucocutaneous candidiasis (CMC). Secondary immune deficiencies are most often due to human immunodeficiency virus (HIV) infection, antibiotic use and immunosuppressive treatment (steroids, chemotherapy). Read More

Front Immunol 2017 14;8:820. Epub 2017 Jul 14.

Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, United States.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator () mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with gain-of-function (GOF) mutations also develop CMC and autoimmunity; they exhibit increased STAT1 protein levels at baseline and STAT1 phosphorylation (pSTAT1) upon interferon (IFN)-γ stimulation relative to healthy controls. AIRE interacts functionally with a protein that directly regulates STAT1, namely protein inhibitor of activated STAT1, which inhibits STAT1 activation. Read More

Zhonghua Er Ke Za Zhi 2017 Jul;55(7):544-545

Presse Med 2017 Sep 3;46(9):853-863. Epub 2017 Jul 3.

Polyclinique Aguilera, 21, rue de l'Estagnas, 64200 Biarritz, France.

Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. Read More

Endocr Regul 2017 Apr;51(2):114-116

.

A 31-year-old lady, diagnosed to have premature ovarian failure in the gynecology clinic, was referred for endocrine assessment because of an abnormal thyroid function test. Clinical examination revealed hypotension, and fungal skin infection under her atrophic breasts. Thyroid stimulating hormone (TSH) level was very high. Read More

Nihon Rinsho Meneki Gakkai Kaishi 2017 ;40(2):109-117

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

Chronic mucocutaneous candidiasis (CMC) is an infectious phenotype which is characterized by recurrent or persistent infections affecting the nails, skin, and oral and genital mucosae caused by Candida species. Th17 cells produce interleukin-17 (IL-17) and play an important role in host mucosal immunity to Candida. Recent studies revealed that an impairment of IL-17 immunity underlies development of CMC. Read More

J Allergy Clin Immunol 2018 Feb 7;141(2):704-717.e5. Epub 2017 Jun 7.

Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, Wash. Electronic address:

Background: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder. Read More

Acta Microbiol Immunol Hung 2017 Jun 9;64(2):191-201. Epub 2017 Jun 9.

1 Department of Allergy and Clinical Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences , Tehran, Iran.

Heterozygous gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) have increasingly been identified as a genetic cause of autosomal-dominant (AD) chronic mucocutaneous candidiasis (CMC). In this article, we describe a 33-year-old man who experienced chronic refractory candidiasis, recurrent otitis media, and pneumonia resulting in bronchiectasis, severe oral and esophageal candidiases with strictures associated with hypothyroidism and immune hemolytic anemia. His son also suffered from persistent candidiasis, chronic diarrhea, poor weight gain, and pneumonia that resulted in his demise because of sepsis. Read More

J Clin Immunol 2017 Jul 8;37(5):486-495. Epub 2017 Jun 8.

Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Purpose: Primary immunodeficiency diseases (PIDDs) are rare inherited diseases that impair the human immune system. We established a multicolor flow cytometric assay to comprehensively evaluate the immune status and immunological characteristics of patients with PIDDs.

Methods: Fifty-nine normal controls and 75 patients with PIDDs, including X-linked severe combined immunodeficiency (X-SCID), X-linked agammaglobulinemia (XLA), X-linked hyper IgM syndrome (X-HIGM), ataxia telangiectasia (AT), Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES), and chronic mucocutaneous candidiasis disease (CMCD), were enrolled in this study. Read More

Immunogenetics 2017 10 24;69(10):643-651. Epub 2017 May 24.

Department of Endocrinology, China Three Gorges University & Yichang Central People's Hospital, Yi Ling Road 181, Yichang, 443003, China.

Autoimmune polyendocrine syndrome type 1 (APS-1, OMIM 2403000) is a rare autosomal recessive disease that is caused by autoimmune regulator (AIRE). The main symptoms of APS-1 are chronic mucocutaneous candidiasis, autoimmune adrenocortical insufficiency (Addison's disease) and hypoparathyroidism. We collected APS-1 cases and analysed them. Read More

Front Immunol 2017 18;8:377. Epub 2017 Apr 18.

Division of Pediatric Rheumatology, Penn State Children's Hospital, Hershey, PA, USA.

Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) is a rare disorder of immune dysregulation caused by mutations in the autoimmune regulator () gene. Individuals affected with APECED develop a clinical syndrome characterized by ectodermal abnormalities, autoantibody production, and organ-specific autoimmune manifestations. Inflammatory arthritis is usually not described as a part of the syndrome, and only sporadic cases are reported. Read More

Curr Allergy Asthma Rep 2017 May;17(5):31

From the Department of Pediatrics, Allergy-Immunology and Pediatric Rheumatology Division, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.

Purpose Of Review: Healthy children may develop candidal infections as the result of exposure to antibiotics or corticosteroids, but chronic candidiasis in children after the newborn period is unusual. Chronic mucocutaneous candidiasis (CMC) refers to a group of conditions characterized by recurrent or persistent infections with Candida species, particularly Candida albicans. CMC is a phenotype observed in a spectrum of immunologic disorders, some with endocrinologic and autoimmune features. Read More

Respir Med 2017 May 22;126:39-45. Epub 2017 Mar 22.

Department of Pediatrics and Pediatric Pulmonary Unit, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.

Background: In a substantial number of patients with non-cystic fibrosis (CF) bronchiectasis an etiology cannot be found. Various complex immunodeficiency syndromes account for a significant portion of these patients but the mechanism elucidating the predisposition for suppurative lung disease often remains unknown.

Objective: To investigate the cause and mechanism predisposing a patient to severe bronchiectasis. Read More

Front Immunol 2017 13;8:274. Epub 2017 Mar 13.

Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Division of Clinical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.

Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency characterized by persistent or recurrent skin and mucosal surface infections with species. Different gene mutations leading to CMC have been identified. These include various heterozygous gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 () that are not only associated with infections but also with autoimmune manifestations. Read More

J Biol Chem 2017 04 3;292(15):6240-6254. Epub 2017 Mar 3.

From the Department of Technology Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu-Shi, Chiba-Ken, 292-0818.

Gain-of-function (GOF) mutations in the gene are critical for the onset of chronic mucocutaneous candidiasis (CMC) disease. However, the molecular basis for the gain of STAT1 function remains largely unclear. Here, we investigated the structural features of GOF residues to better understand the impact of these pathogenic mutations. Read More

Ital J Pediatr 2017 Jan 19;43(1):11. Epub 2017 Jan 19.

Department of Microbiology and Immunology- UNC Hospitals Children's Specialty Clinic- Chapel Hill, Chapel Hill, NC, USA.

Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE gene mutation. It is characterized by the association of multiple autoimmune diseases, with a classical triad including chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical failure. Its clinical spectrum has significantly enlarged in the last years with the apparence of new entities. Read More

Bull Soc Pathol Exot 2017 Feb 11;110(1):80-84. Epub 2017 Feb 11.

Service de parasitologie-mycologie, Hôpital Saint Antoine, 184 rue du Faubourg Saint Antoine, 75012, Paris, France.

Various infectious agents are classical risk factors for cancer including bacteria, viruses and parasites. There is less evidence concerning the implication of fungal infection in carcinogenesis. The role of chronic Candida infection in the development of squamous cell carcinoma has been suspected for years. Read More

Clin Immunol 2017 05 2;178:79-85. Epub 2017 Feb 2.

Department of Neurology, University Clinic Essen, Essen, Germany. Electronic address:

Chronic mucocutaneous candidiasis, characterized by persistent or recurrent fungal infections, represents the clinical hallmark in gain-of-function (GOF) signal transducer and activator of transcription 1 (STAT1) mutation carriers. Several cases of intracranial aneurysms have been reported in patients with GOF STAT1 mutation but the paucity of reported cases likely suggested this association still as serendipity. In order to endorse this association, we link the development of intracranial aneurysms with STAT1 GOF mutation by presenting the two different cases of a patient and her mother, and demonstrate upregulated phosphorylated STAT4 and IL-12 receptor β1 upon stimulation in patient's blood cells. Read More

J Allergy Clin Immunol 2017 May 27;139(5):1629-1640.e2. Epub 2017 Jan 27.

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Mass.

Background: Gain-of-function (GOF) mutations in the human signal transducer and activator of transcription 1 (STAT1) manifest in immunodeficiency and autoimmunity with impaired T17 cell differentiation and exaggerated responsiveness to type I and II interferons. Allogeneic bone marrow transplantation has been attempted in severely affected patients, but outcomes have been poor.

Objective: We sought to define the effect of increased STAT1 activity on T helper cell polarization and to investigate the therapeutic potential of ruxolitinib in treating autoimmunity secondary to STAT1 GOF mutations. Read More

Clin Transl Immunology 2016 Dec 2;5(12):e114. Epub 2016 Dec 2.

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

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by spp., mainly . CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Read More

J Allergy Clin Immunol 2017 Aug 6;140(2):553-564.e4. Epub 2017 Jan 6.

Institute of Molecular Medicine "Angelo Nocivelli," University of Brescia, Brescia, Italy; Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy. Electronic address:

Background: Gain-of-function (GOF) mutations affecting the coiled-coil domain or the DNA-binding domain of signal transducer and activator of transcription 1 (STAT1) cause chronic mucocutaneous candidiasis disease. This condition is characterized by fungal and bacterial infections caused by impaired generation of T17 cells; meanwhile, some patients with chronic mucocutaneous candidiasis disease might also have viral or intracellular pathogen infections.

Objective: We sought to investigate the effect of STAT1 GOF mutations on the functioning of natural killer (NK) cells. Read More

J Allergy Clin Immunol Pract 2017 Jul - Aug;5(4):1119-1121. Epub 2017 Jan 5.

Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

J Allergy Clin Immunol 2017 Jul 20;140(1):232-241. Epub 2016 Dec 20.

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

Background: Germline heterozygous mutations in human signal transducer and activator of transcription 1 (STAT1) can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases, or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis. LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil domain (CCD) and DNA-binding domain (DBD). Moreover, 6% of patients with chronic mucocutaneous candidiasis with a GOF STAT1 mutation have mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations. Read More

Allergy Asthma Clin Immunol 2016 2;12:62. Epub 2016 Dec 2.

Acquired Immunodeficiency Research Center, Isfahan University of Medical Science, Khoram St, Isfahan, Iran.

Background: Primary immunodeficiency (PID) is a heterogeneous group of inheritable genetic disorders with increased susceptibility to infections, autoimmunity, uncontrolled inflammation and malignancy. Timely precise diagnosis of these patients is very essential since they may not be able to live with their congenital immunity defects; otherwise, they could survive with appropriate treatment. DNA biobanks of such patients could be used for molecular and genetic testing, facilitating the detection of underlying mutations in known genes as well as the discovery of novel genes and pathways. Read More

Immun Inflamm Dis 2016 Jun 25;4(2):235-243. Epub 2016 May 25.

Molecular Pathology Research Group, Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia.

Introduction: Both autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and the rare thymoma patients with chronic mucocutaneous candidiasis (CMC) have neutralizing autoantibodies to Th17 cytokines and significant defects in production of IL-22 and IL-17F by their T cells. The cause of these defects is unknown. We hypothesized that they might result from autoimmunity against upstream cytokines normally responsible for generating and maintaining Th17 cells. Read More

Proc Natl Acad Sci U S A 2016 12 7;113(51):E8277-E8285. Epub 2016 Dec 7.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, 75015 Paris, France;

Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Read More

Int J Mol Sci 2016 Dec 1;17(12). Epub 2016 Dec 1.

Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

Autoimmune regulator (Aire) mutations result in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which manifests as multi-organ autoimmunity and chronic mucocutaneous candidiasis (CMC). Indendritic cells (DCs), pattern recognition receptors (PRR), such as Toll-like receptors (TLRs), are closely involved in the recognition of various pathogens, activating the intercellular signaling pathway, followed by the activation of transcription factors and the expression of downstream genes, which take part in mediating the immune response and maintaining immune tolerance. In this study, we found that Aire up-regulated TLR3 expression and modulated the downstream cytokine expression and nuclear factor-κB (NF-κB) of the TLR3 signaling pathway. Read More

Clin Immunol 2017 01 14;174:24-31. Epub 2016 Nov 14.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Heterozygous dominant-negative mutations of STAT1 are responsible for autosomal-dominant Mendelian susceptibility to mycobacterial diseases (AD-MSMD). So far, only 7 mutations have been previously described and are localized to 3 domains: the DNA-binding domain, the SH domain, and the tail segment. In this study, we demonstrated the first coiled-coil domain (CCD) mutation of c. Read More