Recurrent, Severe Aphthous Stomatitis and Mucosal Ulcers as Primary Manifestations of a Novel STAT1 Gain-of-Function Mutation

We report here on a 31 years old female patient suffering from severe mucosal aphthous mucositis and ulcers and recurrent herpes simplex for decades. We found a previously unknown heterozygous sequence variant in STAT1 (c.1219C>G; L407V) affecting the DNA-binding domain of the protein in the patient and her 4 years old daughter. We found this mutation gain-of-function (GOF) by using immunoblot and luciferase assays. We detected low proportion of IL-17A-producing CD4+ T cell lymphocytes by using intracellular staining and flow cytometry. Candida-induced secretion of IL-17A and IL-22 by mononuclear cells from the patient was markedly decreased compared to controls. These data suggest that the novel mutant allele may result in impaired differentiation of CD4+ T cells to CD4+/IL-17+ cells. The clinical phenotype of the disease in this patient was unique as it was dominated primarily by severe aphthous stomatitis and ulcerative esophagitis and only partly by typical CMC resulting in diagnostic delay. We suggest that patients with severe recurrent aphthous stomatitis and esophagitis should be evaluated for STAT1 GOF mutation. Based on the broad clinical spectrum of the disease, we also suggest that CMC and CMC disease may not be an appropriate term to define clinically STAT1 GOF mutation.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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CONCLUSION: prompt diagnosis, through fundus examination and FA, and proper antiviral therapy were the mainstays to counteract the posterior uveitis. Nowadays, vaccination is a safe weapon to efficaciously reduce the ZVZ incidence among general population. PMID: 32644840 [PubMed - as supplied by publisher]
Source: Ocular Immunology and Inflammation - Category: Allergy & Immunology Tags: Ocul Immunol Inflamm Source Type: research
Publication date: Available online 9 July 2020Source: Journal of Global Antimicrobial ResistanceAuthor(s): Amirhossein Davari, Iman Haghani, Fozieh Hassanmoghadam, Mojtaba Nabili, Tahereh Shokohi, Mohammad Taghi Hedayati, Shafigheh Shabanzadeh, Maryam Moazeni
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
Authors: Kleymann J, Schütz C, Körholz J, Taube F, Vogler M, Halank M, Kolditz M, Langner S, Geberzahn L, Holotiuk O, Roesler J, Koschel D Abstract Chronic granulomatous disease (CGD) should be considered as a differential diagnosis in children and adolescents with frequent infections, especially when caused by certain specific pathogens.This case report describes a 64-year-old female with multiple recurrent and complicated bronchopulmonary infections, caused by common, but also rare pathogens, autoimmune phenomena, malignancies and recurrent organizing pneumonia (OP) with granulomas. Finally, the patient...
Source: Pneumologie - Category: Respiratory Medicine Tags: Pneumologie Source Type: research
Authors: Shay E, Sangwan N, Padmanabhan R, Lundy S, Burkey B, Eng C Abstract The etiology of head and neck squamous cell carcinoma (HNSCC) is not fully understood. While risk factors such as positive human papilloma virus (HPV) status, smoking and tobacco use have been identified, they do not account for all cases of the disease. We aimed to characterize the bacteriome, mycobiome and mycobiome-bacteriome interactions of oral wash in HNSCC patients and to determine if they are distinct from those of the oral wash of matched non-HNSCC patients. Oral wash samples were collected from 46 individuals with HNSCC and 46 co...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic H...
Source: Virology Journal - Category: Virology Authors: Tags: Research Source Type: research
Abstract Pemphigus is a group of autoimmune bullous skin diseases that result in significant morbidity. As for other multifactorial autoimmune disorders, environmental factors may trigger the disease in genetically susceptible individuals. The goals of this review are to summarize the state of knowledge about the genetic variation that may affect the susceptibility and pathogenesis of pemphigus vulgaris and pemphigus foliaceus - both the endemic and the sporadic forms -, to compare and discuss the possible meaning of the associations reported, and to propose recommendations for new research initiatives. Understand...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Genet Mol Biol Source Type: research
Traditional Chinese medicine (TCM) with the characteristics of “multi-component-multi-target-multi-pathway” has obvious advantages in the prevention and treatment of complex diseases, especially in the aspects of “treating the same disease with different treatments”. However, there are still some problems such as unclear substance basis and molecular mechanism of the effectiveness of formula. Network pharmacology is a new strategy based on system biology and poly-pharmacology, which could observe the intervention of drugs on disease networks at systematical and comprehensive level, and especially su...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Excessive activation of the proinflammatory cytokine tumor necrosis factor-α (TNFα) is a major cause of autoimmune diseases, including rheumatoid arthritis. TNFα induces immune responses via TNF receptor 1 (TNFR1) and TNFR2. Signaling via TNFR1 induces proinflammatory responses, whereas TNFR2 signaling is suggested to suppress the pathophysiology of inflammatory diseases. Therefore, selective inhibition of TNFR1 signaling and preservation of TNFR2 signaling activities may be beneficial for managing autoimmune diseases. To this end, we developed a TNFR1-selective, antagonistic TNFα mutant (R1antTNF)....
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Immunology Source Type: research
ConclusionsBullous pemphigoid patients need screening for comorbid health conditions even though treatment options do not seem to be associated with these comorbidities.
Source: Archives of Dermatological Research - Category: Dermatology Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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