A gain-of-function mutation of STAT1: A novel genetic factor contributing to chronic mucocutaneous candidiasis

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. The immunological workup showed that an inverse CD4/CD8 ratio and serum immunoglobulins were all within normal ranges. The laboratory data revealed failure in response to Candida lymphocyte transformation test. In addition, by Sanger sequencing method, we found a heterozygous mutation, Thr385Met (T385M), located in the DNA-binding domain of STAT1, which was previously shown to be GOF. These findings illustrate the broad and variable clinical phenotype of heterozygous STAT1 GOF mutations. However, more clinical information and phenotype–genotype studies are required to define the clinical phenotype caused by AD STAT1 GOF

Food-induced Allergic Rhinitis

Food allergy is estimated about 8% in children. The relationship between food and manifestation of allergy symptoms and its confirmation for accurate diagnosis is very important. Allergic rhinitis is a common disease with a prevalence of 40% among different societies. The prevalence of food-induced allergic rhinitis appears to be less than 1 percent. Food reactions often lead to rhinitis symptoms at a no immunologic nature. Although the role of food and fruits in developing allergic rhinitis is not clearly identified, in a very small percentage of patients, rhinitis is the clinical manifestation of food allergy

Evaluation of Immunological Parameters in Purified Protein Derivative Positive Tuberculin Workers

Objective(s): According to the occupationally risk of infection in staff workers who have direct contact with mycobacterium species, we investigated their immunological parameters and compared with healthy purified protein derivative (PPD) negative volunteers.   Materials and Methods : We investigated 20 PPD positive volunteers working at Tuberculin Unit of Razi Vaccine and Serum Research Institute and PPD negative healthy controls with no exposure or history of active tuberculosis. The percentages of circulating lymphocyte subpopulations were detected by flowcytometry. IL-4 and IFN-γ production levels were measured by ELISA in supernatants of PPD-stimulated peripheral blood mononuclear cells (PBMCs) culture. Results : Tuberculin workers showed an increase in IFN-γ level and significant decrease of CD4+ T cells percentage and CD4/CD8 ratio compared to PPD negative normal individuals. However the IL-4 production and percentage of other lymphocyte population has been unchanged. Discussion: These observations suggest that the immunological parameters of tuberculin workers with PPD positive reaction, who are occupationally exposed to mycobacterium antigens, could be changed. Future studies will be directed towards cytokine networking and regulatory lymphocytes, which will help us validate the significant data presented in this study

Cystic fibrosis and congenital adrenal hyperplasia: A rare occurrence with diagnostic dilemmas, similarities and contradictions

Cystic fibrosis (CF) is a hereditary syndrome composed of exocrine gland dysfunction involving multiple systems which if untreated may result in chronic respiratory infections, pancreatic enzyme deficiency and failure to thrive. The association between CF and other inherited diseases or congenital anomalies is rare. We describe a rare case of CF with concomitant congenital adrenal hyperplasia (CAH). 21- Hydroxylase deficiency accounts for most CAH cases. Varity in clinical phenotypes depends on the amount of enzymatic activity which in turn depends on different combination of gene mutations. The genes of CAH and CF are located in different locations. The chance of these diseases coexisting in our patient would be a rare combination. However, such a case will be more frequent in our population than others because of consanguineous marriage and common ancestors. There are diagnostic difficulties, similarities and contradictions between two diseases and they are pointed out

Circulating level of CD4+ CD25+ FOXP3+ T cells in patients with chronic urticaria

Background CD4+ CD25+ T-regulatory (Treg) cells play critical roles in maintaining peripheral tolerance and preventing autoimmunity. As characteristics of Treg cells have not been precisely investigated in chronic urticaria (CU) yet, this study was performed. Objective To determine the frequencies of circulating CD4+ CD25+ FOXP3+ T cells and serum levels of interleukin (IL)-10, transforming growth factor (TGF)-β, and IL-17 in patients with chronic autoimmune urticaria and chronic idiopathic urticaria compared to healthy controls. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from patients with CU and healthy controls. The frequency of CD4+ CD25+ T cells in PBMCs and expression levels of FOXP3 were detected by flow cytometry. The serum levels of IL-10, TGF-β, and IL-17 were measured by enzyme-linked immunosorbent assay. Results A significant decrease in the percentage of circulating CD4+ CD25+ FOXP3+ T cells was detected in patients with CU, compared to control subjects. However, no significant difference was detected on the serum levels of IL-10, TGF-β, and IL-17 between patients with CU and control subjects. Conclusions This study demonstrated that the frequency of Treg cells in PBMCs was decreased in patients with CU. Further studies are needed to clarify the exact role of Treg cells in the pathogenesis of CU and factors regulating their function

An observational prospective study on incidence of Ventilator Associated Pneumonia (VAP) in patients with continuous endotracheal-tube cuff-pressure control system

Background: Ventilator Associated Pneumonia (VAP) is one of the most important nosocomial infections in the Intensive Care Unit (ICU), causing significant morbidity and mortality. Apart from other measures, prevention of the leakage of oro-pharyngeal secretions in the lungs, using Endotracheal Tube Cuff Pressure Control System (ETCPCS) is an important upcoming strategy. Aims: In order to evaluate the significance of continuous cuff pressure monitoring in intubated patients. Methods: A total of fifty patients, of either gender with age >18 years who were mechanically ventilated for more than 48 hours, after intubation maintaining standard aseptic techniques and adhering strictly to VAP prevention bundle,were observed. Pressure in the cuff was maintained around 20 to 30 cms H20. Patients’ vitals, general and systemic examination, ventilator parameters and other investigations like leucocyte count, arterial blood gas measurements, chest X-Ray, and tracheal tube culture were recorded. Results: The incidence and the incidence density of VAP were found to be 24% and 26.37 respectively. Out of the 12 (24%) confirmed VAP patients, 4 (33%) were early onset whereas 8(66%) were categorized as late onset VAP. Conclusion: Continuous cuff pressure measurement may be associated with the incidence of VAP in the lower range whereas the significance of other factors like the adequacy of nursing staff in the ICU cannot be ruled out

The role of molecular diagnosis in anaphylactic patients with dual or triple-sensitization to Hymenoptera venoms

Abstract Background The poly-sensitization to Hymenoptera venom makes it difficult to select genuine allergens for immunotherapy and increases patients’ costs. The objective of this study was to determine the culprit allergen in dual or triple-sensitized patients to three Hymenoptera venoms through molecular diagnosis and evaluating the results of incorporating the molecular diagnosis with skin tests. Methods Thirty-two patients with anaphylactic reactions and dual or triple-sensitization to Hymenoptera venoms in skin tests entered this study. IgE-sensitization to whole extracts and molecules of Apis mellifera (Api m), Vespula vulgaris (Ves v), and Polistes dominulus (Pol d) was evaluated utilizing ALEX or ImmunoCAP. Results Twenty-nine patients (90.6%) were male. IgE-sensitization to at least one of the allergenic molecules related to Apis mellifera, Vespula vulgaris, and Polistes dominulus was seen in 59.4, 53.1, and 21.9%, respectively. Among 32 patients, 14 (43.8) and 8 (25%), were mono-sensitized to Api m and Ves v components in ALEX, respectively. Double sensitization to Hymenoptera was identified in 18.8% of patients in ALEX. Api m 1+/Api m 2−/Api m 10− and Ves v 1+/Ves v 5+ demonstrated the most prevalent sensitizations patterns in our patients. Conclusions The molecular diagnosis of IgE-sensitization to Hymenoptera venoms can be valuable, especially in patients who show dual or triple-sensitization in skin tests, as the ALEX results revealed mono and double-sensitization to Hymenoptera venoms in 22 and 6 patients, respectively. Regarding the high cost and adverse reactions of venom immunotherapy, especially for two or three venoms, incorporating the molecular diagnosis alongside skin tests for accurate diagnosis of the culprit venom could help decrease costs for patients

Otitis Media with Effusion in Children and the Impact of Risk Factors on Serum Cytokine Levels

Introduction:To evaluate the role of allergic-type and infectious-type cytokines in children with chronic otitis media with effusion (OME) Materials and Methods:We investigated serum levels of interleukins (IL)-4, IL-5, and IL-13, along with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), by enzyme-linked immunosorbent assay (ELISA) in 35 children with OME and 28 healthy controls. Results:Children with OME had significantly higher levels of IL-5 in comparison with the control group, ranging from 1 pg/ml in cases to 0.04 pg/ml in controls (P=0.009). However, after adjusting for confounding variables, there was no significant difference in serum levels of IL-13, IL-4, IFN-γ, or TNF-α between the two groups (P=0.287, P=0.627, P=0.793, and P=0.217, respectively) Conclusions:The findings of this study suggest that in comparison with the control group, serum IL-5 levels were elevated in OME cases