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Liu L.,University of Paris Descartes | Okada S.,Rockefeller University | Kong X.-F.,Rockefeller University | Kreins A.Y.,Rockefeller University | And 70 more authors.
Journal of Experimental Medicine | Year: 2011

Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity. © 2011 Liu et al.


Sheikh Sajjadieh M.-R.,National Medical Academy for Post Graduate Education | Kuznetsova L.V.,National Medical Academy for Post Graduate Education | Bojenko V.B.,Ukrainian Specialized Dispensaries of Radiation Defend Population
Iranian Journal of Pediatrics | Year: 2012

Objective: Microbiota has an important role in human metabolism, nutrition, immunity, and protection against colonization by pathogenic microorganisms. Radiation can harm the beneficial members of the gastrointestinal tract flora. Methods: Our study included 75 rural children aged 4-18 years, who lived in contaminated area exposed to natural environmental radiation with clinical symptoms of irritable bowel syndrome and 20 healthy urban participants aged 5-15 as control group. The intestinal bacterial microbiota was examined from stool samples. Findings: Our results indicated the population levels of microbiota such as Enterobacter, Enterococcus, Lactobacillus and Bifidbacterium in caecal contents in 61 subjects (81.3%) was significantly less than in control group. Conclusion: We investigated alternation of the intestinal microbiota affected by ionizing radiation in children with clinical symptoms of irritable bowel syndrome. © 2012 by Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, All rights reserved.


Sheikh Sajjadieh M.R.,National Medical Academy for Post Graduate Education | Kuznetsova L.V.,National Medical Academy for Post Graduate Education | Bojenko V.B.,Ukrainian Specialized Dispensaries of Radiation Defend Population
Toxicology and Industrial Health | Year: 2010

Adverse health effect of low radiation is clear. The aim of this study was to determine effect of internal low radiation on innate immune status in Ukrainian children with spastic colitis as a result of Chernobyl disaster. The test population consisted of 95 participants: 75 rural participants with clinical symptom of irritable bowel syndrome, aged 4 to 18, who lived in a contaminated area exposed to radio nucleotide due to the disaster in reactor in Chernobyl nuclear power plant (categorized in three groups) and 20 healthy urban participants from Kiev, aged 5 to 15, as the control group. Internal radiation activity has been measured by 3-ray spectrometry. Peripheral blood leukocytes were analyzed for CD16+ subset, serum concentration of circulation immune complex was measured by the polyethylene glycol method. Phagocytic activity function was assessed by using latex article and phagocytic index were calculated. p < 0.05 was considered significant. Percent of CD16+ cell in groups II and III increased significantly in comparison to control group (p < 0.05). Concentration of circulating immune complexes increased significantly in all study groups compared to control group (p < 0.001). Phagocytes activity and phagocyte index decreased significantly in all study groups in comparison to control group (p < 0.001). The innate immune status of study groups has changed. Our data have demonstrated that this change may be related to radioactivity from technogenic pollution due to the disaster in reactor in Chernobyl nuclear power plant. © The Author(s) 2010.


Sajjadieh M.R.S.,National Medical Academy for Post Graduate Education | Kuznetsova L.,National Medical Academy for Post Graduate Education | Bojenko V.,Ukrainian Specialized Dispensaries of Radiation Defend Population
Iranian Journal of Immunology | Year: 2012

Background: The effect of low dose radiation on immune system is shown. Ionizing radiation can affect cytokine production and polarization of T helper cells. Objective: The current study focused on ionizing radiation in Ukrainian children residing in a contaminated area with clinical irritable bowel syndrome. Method: Our study included 75 rural children population aged 4-18 yrs, who lived in a contaminated area exposed to natural environmental radiation with clinical irritable bowel syndrome (categorized in three groups) and 20 rural children participants aged 5-15 yrs who were living in areas with similar levels of radioactive contamination without clinical irritable bowel syndrome as control group. Internal radiation activity was measured by gamma-ray spectrometry. Serum levels of IL-4 and IFN-γ were measured by enzyme linked immunosorbent assay. Results: A trend towards increased levels of IL-4 was observed in children with clinical irritable bowel syndrome. In these children, IFN-γ levels were lower than that of the control group. Conclusion: The IBS symptoms in Ukrainian children residing in a contaminated area may have stemmed from Th1 to Th2 immune deviation and differential expression of IL-4 and IFN-γ.


Sheikh Sajjadieh M.R.,National Medical Academy for Post Graduate Education | Kuznetsova L.V.,National Medical Academy for Post Graduate Education | Bojenko V.B.,Ukrainian Specialized Dispensaries of Radiation Defend Population
Toxicology and Industrial Health | Year: 2011

The aim of this study is to determine humoral immune status in Ukrainian children with clinical symptoms of irritable bowel syndrome 23 years after the Chernobyl disaster. Method and material: The test population consisted of 95 participants: 75 rural patients aged 4-18, who lived in a contaminated area exposed to natural environmental radiation (falling under three groups) and 20 healthy urban participants from Kiev aged 5-15 as a control group. Internal radiation activity has been measured by gamma-ray spectrometry. B-lymphocytes population was analyzed with monoclonal antibody against antigen CD22 +. Serum immunoglobulins were evaluated by enzyme-linked immunosorbent assay (ELISA) method. p < 0.05 was considered significant. Result: The percentage of CD22+ in study groups is increased significantly in comparison to control group at p < 0.05. Reduced serum immunoglobulins levels have developed in the majority of the participants. Conclusion: Humoral immune status of study groups with clinical symptom of irritable bowel syndrome residing in a contaminated area has changed. © 2011 The Author(s).


Sheikh Sajjadieh M.R.,National Medical Academy for Post Graduate Education
Iranian Journal of Radiation Research | Year: 2016

External exposed radiation may play an important role in pathogens of irritable bowel syndrome (IBS), although is thought to arise due to a combination of gene c and environmental factors. The result is dysregulated immune responses due to alteration in the gut microbiota population and the subsequent development of gut inflammation. It has recently been shown that the effect of ionizing radiation on T-cell lymphocytes might be a risk factor of IBS. This article tries to discuss the effects of low dose radiation on alternation in the population of beneficial members of the gastrointestinal tract flora. The result may be activated inflammatory response of mucosal immune status induced Toll like receptors. Lipopolysaccharides produced by most gram-negative bacteria of gastroinestinal tract play a role in the initiation and progress of the Toll like receptors in the intestines. Circulating cytokines and soluble receptors released by activated Th2 can regulate neuronal function via endocrine mechanisms. Disturbance of the cytokine-mediated interaction between cells may lead to neuronal dysfunction or sensory dysfunction, motor dysfunction, or both sensory and motor dysfunction in patient with IBS. © 2016, Novim Medical Radiation Institute. All rights reserved.


Sheikh Sajjadieh M.R.,National Medical Academy for Post Graduate Education | Kuznetsova L.V.,National Medical Academy for Post Graduate Education | Bojenko V.B.,National Medical Academy for Post Graduate Education
Toxicology and Industrial Health | Year: 2010

Irritable bowel syndrome is observed mostly in Ukrainian children and may be related to adverse health effects as a result of the Chernobyl disaster. The aim of this study was to determine status of T-cell population lymphocytes in children with clinical symptom of irritable bowel syndrome. The test population consisted of 95 participants: 75 rural patients aged 4 to 18 who lived in a contaminated area exposed to natural environmental radiation with clinical symptom of irritable bowel syndrome (categorized in three groups) and 20 healthy urban participants from Kiev aged 5 to 15 as control group. Internal radiation activity has been measured by γ-ray spectrometry. Peripheral blood leukocytes were analyzed for T-lymphocytes subset such as T-lymphocytes (CD3+), T-helper (CD4+) and T-cytotoxic (CD8+) and then CD4/CD8 ratio was calculated. Percentage of CD3+ and CD4+ in all study groups decreased significantly in comparison to control group (p < 0.001). Percentage of CD8+ increased significantly in all study groups in comparison to control group (p < 0.05). The CD4/CD8 ratio decreased significantly all study groups in comparison to control group (p < 0.001). Cellular immune status of study groups that are residing in a contaminated area has changed. Our data have demonstrated that this change may be related to a higher incidence of children with irritable bowel syndrome. © The Author(s) 2010.


PubMed | National Medical Academy for Post Graduate Education
Type: Journal Article | Journal: Toxicology and industrial health | Year: 2010

Irritable bowel syndrome is observed mostly in Ukrainian children and may be related to adverse health effects as a result of the Chernobyl disaster. The aim of this study was to determine status of T-cell population lymphocytes in children with clinical symptom of irritable bowel syndrome. The test population consisted of 95 participants: 75 rural patients aged 4 to 18 who lived in a contaminated area exposed to natural environmental radiation with clinical symptom of irritable bowel syndrome (categorized in three groups) and 20 healthy urban participants from Kiev aged 5 to 15 as control group. Internal radiation activity has been measured by gamma-ray spectrometry. Peripheral blood leukocytes were analyzed for T-lymphocytes subset such as T-lymphocytes (CD3(+)), T-helper (CD4(+)) and T-cytotoxic (CD8(+)) and then CD4/CD8 ratio was calculated. Percentage of CD3(+) and CD4(+) in all study groups decreased significantly in comparison to control group (p < 0.001). Percentage of CD8(+) increased significantly in all study groups in comparison to control group (p < 0.05). The CD4/CD8 ratio decreased significantly all study groups in comparison to control group (p < 0.001). Cellular immune status of study groups that are residing in a contaminated area has changed. Our data have demonstrated that this change may be related to a higher incidence of children with irritable bowel syndrome.

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