J Eur Acad Dermatol Venereol 2017 Jun 16. Epub 2017 Jun 16.

Dermatology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

We report a family in which 3 of 5 children as well as the mother, had a gain-of-function (GOF) mutation in the signal transducer and activator of transcription (STAT1) associated with early-onset rosacea and demodicidosis. The proband case (Fig. 1) was a 13-year-old boy of non-consanguineous parents, known for a hypothyroidism, failure to thrive and chronic mucocutaneous candidiasis (CMC) since he was 5-6 years old. 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 2017 Jun 7. Epub 2017 Jun 7.

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

Background: Gain of function mutations in signal transducer and activator of transcription 1 (GOF-STAT1) cause a 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 utilized in some patients with more severe symptoms to treat and cure the disorder. Read More

Acta Microbiol Immunol Hung 2017 Jun 9:1-11. 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 Jun 8. 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 May 24. 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 (AIRE) 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 Candida 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 (STAT1) that are not only associated with infections but also with autoimmune manifestations. Read More

J Biol Chem 2017 Apr 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 STAT1 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 STAT1 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 May 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 TH17 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 Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Read More

J Allergy Clin Immunol 2017 Jan 6. 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 TH17 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 Jan 5. 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 2016 Dec 14. Epub 2016 Dec 14.

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 Dec 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 Jan 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 SH2 domain, and the tail segment. In this study, we demonstrated the first coiled-coil domain (CCD) mutation of c. Read More

Int J Dermatol 2017 Feb 3;56(2):e30-e33. Epub 2016 Nov 3.

Department of Dermatology, Peking University First Hospital, Beijing, China.

J Leukoc Biol 2017 Jan 1;101(1):29-38. Epub 2016 Nov 1.

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

STAT proteins are a family of transcription factors that mediate cellular response to cytokines and growth factors. Study of patients with familial susceptibility to pathogens and/or autoimmune diseases has led to the identification of 7 inherited disorders that are caused by mutations of 4 STAT family genes. Homozygous or compound heterozygous mutations of STAT1 lead to complete or partial forms of STAT1 deficiency that are associated with susceptibility to intracellular pathogens and herpetic infections. Read More

J Oral Pathol Med 2017 May 22;46(5):393-397. Epub 2016 Oct 22.

Dipartimento di Scienze Mediche e Sanità Pubblica, Università degli Studi di Cagliari, Cagliari, Italy.

Objective: The aim of this study was to investigate whether a variation in the genomic copy number (CNV) of the β-defensin cluster could be associated with the pre-disposition to chronic mucocutaneous candidiasis (CMC) in Sardinian APECED patients.

Subjects And Methods: The β-defensin copy number variation was determined by MLPA analysis in 18 Sardinian APECED patients with CMC and in 21 Sardinian controls. Statistical analyses were performed with one-way ANOVA test. Read More

Mycopathologia 2017 Apr 22;182(3-4):397-402. Epub 2016 Sep 22.

Department of Dermatology and Venerology, The 3rd Affiliated Hospital of Southern Medical University, 183 West Zhongshan Rd, Guangzhou, 510630, China.

Candida albicans is the most common pathogen that causes balanoposthitis. It often causes recurrence of symptoms probably due to its antifungal resistance. A significant number of balanitis Candida albicans isolates are resistant to azole and terbinafine antifungal agents in vitro. Read More

JCI Insight 2016 Aug;1(13)

Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE mutations. It classically presents with chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues; hypoparathyroidism and adrenal insufficiency are most common. Developing any two of these classic triad manifestations establishes the diagnosis. Read More

J Allergy Clin Immunol 2017 Mar 20;139(3):933-949. Epub 2016 Aug 20.

Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, Australia. Electronic address:

Background: Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency caused by autosomal recessive loss-of-function mutations in DOCK8. This disorder is characterized by recurrent cutaneous infections, increased serum IgE levels, and severe atopic disease, including food-induced anaphylaxis. However, the contribution of defects in CD4(+) T cells to disease pathogenesis in these patients has not been thoroughly investigated. Read More

Clin Exp Allergy 2016 Dec 18;46(12):1564-1574. Epub 2016 Sep 18.

Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.

Background: STAT1 mutations cause chronic mucocutaneous candidiasis (CMC), while STAT3 mutations cause hyper-IgE syndrome (HIES). CMC and HIES patients have T helper (Th) 17 defects suffering from mucosal Candida infections, but only patients with HIES show an allergic phenotype with eczema, eosinophilia and high IgE levels.

Objective: We investigated whether differential Th2 and Th9 responses may explain the clinical differences. Read More

Int J Mol Sci 2016 Jul 12;17(7). Epub 2016 Jul 12.

Infectivology and Clinical Trials Area, Children's Hospital Bambino Gesù, Rome 00146, Italy.

Type 1 autoimmune polyglandular syndrome (APS1) is a rare autosomal recessive disease, caused by mutations in the autoimmune regulator gene (AIRE); the encoded Aire protein plays an important role in the establishment of the immunological tolerance acting as a transcriptional regulator of the expression of organ-specific antigens within the thymus in perinatal age. While a high prevalence for this rare syndrome is reported in Finland and Scandinavia (Norway), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) cohorts of patients are also detected in continental Italy and Sardinia, among Iranian Jews, as well as in other countries. The syndrome is diagnosed when patients present at least two out of the three fundamental disorders including chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Read More

J Med Assoc Thai 2016 Apr;99(4):406-11

Background: Increasing numbers of mucocutaneous infection due to non-albicans species of Candida (N-CA) had been reported. Laboratory based studies showed multidrug resistance in N-CA population.

Objective: Demonstrate epidemiology, clinical characteristics, sites of infection, and treatment outcomes of mucocutaneous candidiasis caused by N-CA at a dermatologic clinic, including statistical evaluation data between N-CA and C. Read More

J Clin Immunol 2016 Oct 5;36(7):641-8. Epub 2016 Jul 5.

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

Purpose: Loss and gain-of-function (GOF) mutations in human signal transducer and activator of transcription 1 (STAT1) lead to distinct phenotypes. Although recurrent infections are common to both types of STAT1 mutations, GOF mutations are distinguished by chronic mucocutaneous candidiasis and autoimmunity. However, the clinical spectra of STAT1 GOF mutations continue to expand. Read More

Clin Dermatol 2016 Jul-Aug;34(4):487-94. Epub 2016 Mar 2.

Department of Dermatology, University of California at Davis School of Medicine, Sacramento, CA. Electronic address:

Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. Read More

J Clin Endocrinol Metab 2016 Aug 2;101(8):2975-83. Epub 2016 Jun 2.

Department of Clinical Science (Ø.B., B.E.O., E.B., B.G.N., L.B., P.M.K., K.Lo., A.B.W., E.S.H.), University of Bergen, 5021 Bergen, Norway; Department of Medicine (Solna) (N.L., O.K.), Karolinska Institutet, 171 76 Stockholm, Sweden; Science for Life Laboratory (N.L.), Department of Medical Sciences, University of Uppsala, 751 05 Uppsala, Sweden; Department of Medicine (M.M.E., K.Lo., E.S.H.), Haukeland University Hospital, 5021 Bergen, Norway; Department of Medicine (K.Li.,), Akershus University Hospital, 1474 Nordbyhagen, Norway; Department of Endocrinology (K.Li., A.P.J.), Oslo University Hospital, 0372 Oslo, Norway; Department of Pediatrics (A.G.M.), Oslo University Hospital, 0424 Oslo, Norway; Division of Internal Medicine (J.S.), University Hospital of North Norway, 9019 Tromsø, Norway; Institute of Clinical Medicine (J.S.), University of Tromsø, The Artic University of Norway, 9019 Tromsø, Norway; Department of Endocrinology (K.J.F.), St. Olavs Hospital, 7006 Trondheim, Norway; Department of Medicine (Å.B.), Stavanger University Hospital, 4011 Stavanger, Norway; Department of Medicine (B.G.N.), Haugesund Hospital, 5504 Haugesund, Norway; Department of Medicine (B.M.), Østfold Hospital, 1603 Fredrikstad, Norway; Department of Immunology (M.K.V.), Oslo University Hospital, 0372 Oslo, Norway; University of Oslo (M.K.V.), 0372 Oslo, Norway; Center for Medical Genetics and Molecular Medicine (P.M.K.), Haukeland University Hospital, 5021 Bergen, Norway; Department of Clinical Dentistry (M.C.M.), Faculty of Medicine and Dentistry, University of Bergen, 5021 Bergen, Norway; and Oral Health Centre of Expertise in Western Norway (M.C.M.), 5021 Bergen, Norway.

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse.

Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996-2016). Read More

Clin Microbiol Infect 2016 Aug 26;22(8):681-7. Epub 2016 May 26.

Paris Descartes University, Sorbonne Paris Cité, Infectious Diseases Unit, Necker-Enfants Malades University Hospital, AP-HP, Imagine Institute, Paris, France; Institut Pasteur, Unite de Mycologie Moleculaire, CNRS URA3012, Paris, France; Institut Pasteur, Centre National de Référence Mycoses invasives et Antifongiques, Paris, France.

Incidence of invasive fungal infections increases over time with the rise in at-risk populations; in particular, patients with acquired immunodeficiencies due to immunosuppressive therapies such as anti-tumour necrosis factor-α (TNF-α) treatment, cirrhosis or burns. Some primary immunodeficiencies (PID) can also predispose selectively to invasive fungal diseases. Conversely, some atypical fungal diseases can reveal new PID. Read More

Trends Immunol 2016 Jul 10;37(7):440-50. Epub 2016 May 10.

Departments of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, PA 15216, USA. Electronic address:

Candida albicans is a dimorphic commensal fungus that colonizes healthy human skin, mucosa, and the reproductive tract. C. albicans is also a predominantly opportunistic fungal pathogen, leading to disease manifestations such as disseminated candidiasis and chronic mucocutaneous candidiasis (CMC). Read More

J Infect 2016 Jul 6;72 Suppl:S56-60. Epub 2016 May 6.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Center for Infectious Diseases (RCI), The Netherlands.

Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a rare and severe primary immunodeficiency that is characterized by mucocutaneous fungal infection, autoimmunity, cerebral aneurysms, and oropharyngeal and esophageal cancer. Recently, it was discovered that STAT1 mutations are responsible for AD-CMC. These mutations lead to the inability of STAT1 to be dephosphorylated, resulting in hyperphosphorylation, increased binding to the DNA, and gain of function (GOF) effects on STAT1 signaling. Read More

Blood 2016 Jun 25;127(25):3154-64. Epub 2016 Apr 25.

Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, Paris, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Necker Medical School, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY; Department of Infectious and Tropical Diseases, Necker-Enfants Malades Hospital, AP-HP, Paris, France.

Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Read More

J Pediatr Endocrinol Metab 2016 Aug;29(8):979-83

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also named as autoimmune polyglandular syndrome (APS) type 1, is a rare autosomal recessive disorder caused by mutations in autoimmune regulator (AIRE) gene. It is distinguished by an immune-mediated damage of endocrine tissues, chronic candidiasis, and ectodermal disorder. APECED has been shown to be frequent in some populations including Iranian Jews. Read More

Can J Ophthalmol 2016 Apr;51(2):e55-8

Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Que.

Gene 2016 Jul 6;586(2):234-8. Epub 2016 Apr 6.

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

Recently, gain-of-function (GOF) mutations in the gene encoding signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis (CMC). This case report describes a 10-year-old boy presenting with signs of common variable immunodeficiency (CVID), failure to thrive, impaired neurological development, and a history of recurrent mucocutaneous Candida infections. Sequencing of the STAT1 gene identified a heterozygous missense mutation in exon 7 encoding the STAT1 coiled-coil domain (c. Read More

Data Brief 2016 Jun 23;7:311-5. Epub 2016 Feb 23.

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

This paper describes the heterogeneous clinical phenotype of a cohort of nine patients diagnosed with heterozygous mutations in STAT1. We report data of extended immunophenotyping over time and we show lung damage in four patients. The increased phosphorylation of STAT1 in response to IFNγ and IFNα stimulation proves the gain-of-function nature of the defects. Read More

J Clin Immunol 2016 Apr 9;36(3):204-9. Epub 2016 Mar 9.

Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.

Chronic mucocutaneous or invasive fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive fungal infections with Candida spp., dermatophytes (e. Read More

J Allergy Clin Immunol 2016 Jul 2;138(1):297-9. Epub 2016 Mar 2.

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

PLoS One 2016 5;11(2):e0145888. Epub 2016 Feb 5.

Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.

Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to chronic Candida and fungal dermatophyte infections of the skin, nails and mucous membranes. Molecular epidemiology studies of CMC infection are limited in number and scope and it is not clear whether single or multiple strains inducing CMC persist stably or are exchanged and replaced. We subjected 42 C. Read More

Clin Infect Dis 2016 Apr 19;62(7):951-3. Epub 2016 Jan 19.

Department of Dermatology, Venereology and Allergology.

Clin Infect Dis 2016 Apr 6;62(8):986-94. Epub 2016 Jan 6.

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

Background: Progressive multifocal leukoencephalopathy (PML) is a rare, severe, otherwise fatal viral infection of the white matter of the brain caused by the polyomavirus JC virus, which typically occurs only in immunocompromised patients. One patient with dominant gain-of-function (GOF) mutation in signal transducer and activator of transcription 1 (STAT1) with chronic mucocutaneous candidiasis and PML was reported previously. We aim to identify the molecular defect in 3 patients with PML and to review the literature on PML in primary immune defects (PIDs). Read More

Clin Immunol 2016 Mar 28;164:1-9. Epub 2015 Dec 28.

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

In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). Read More