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Hyper-IgE syndrome (HIES) comprises a group of rare primary immunodeficiencies, which are characterized by extremely high serum IgE levels, eczema, recurrent skin and pulmonary infections.Signal transduction and activator of transcription 3( STAT3)-HIES is the most common type, which is caused by dominant-negative mutations in STAT3.STAT3-HIES confers broad innate and acquired immune defects, defects in skeletal, connective tissue, and vascular functions, causing a clinical phenotype including eczema, staphylococcal and fungal skin and pulmonary infections, scoliosis and minimal trauma fractures, vascular tortuosity and aneurysm.In this article, the advance in diverse clinical manifestations and management strategies of STAT3-HIES was summarized.
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Objective To summarize the clinical and genetic features of children with autosomal dominant and recessive hyperimmunoglobulin E syndrome (HIES). Methods HIES patients were studied at the dermatology department of Beijing Children's Hospital, Capital Medical University were collected, from January 2013 to December 2021, diagnosed by both clinical manifestation and genetic assessment. The general data were summarized, the clinical and genetic characteristics were analyzed, and the similarities and differences between autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES) were compared. Results A total of 7 children with HIES were studied, including 3 cases of AD-HIES and 4 cases of AR-HIES. There were 4 males and 3 females. All children had recurrent eczema-like lesions, recurrent skin and pulmonary infections, and elevated serum IgE and eosinophil levels. The differences between AD-HIES and AR-HIES mainly include: the main cutaneous infection in 3 children with AD-HIES were bacterial infections (such as abscess and impetigo), while in 4 children with AR-HIES, cutaneous infections were mostly severe viral infection (such as verruca vulgaris and molluscum contagiosum). There were pulmonary parenchymal changes (such as pneumatoceles, cyst and atelectasis) in 3 children with AD-HIES, whilst there were no similar changes in the lungs of 4 children with AR-HIES; 75% of children with AR-HIES had allergic diseases (including asthma and food allergy), while there were no reports of allergic diseases in children with AD-HIES. As for manifestations outside of immune system, AD-HIES was more likely to appear facial dysmorphism(such a broad nasal bridge and a high-arched palate). Furthermore, the incidence of tumor in AR-HIES was higher than that in AD-HIES. AD-HIES was mainly caused by the mutation of STAT3 gene, and AR-HIES was mainly caused by the mutation of DOCK8 gene. We reported two new mutation sites of DOCK8 gene c.1798-2A > T and c.874G > A in two cases, respectively. Conclusions For children with clinical manifestations of recurrent eczema-like lesions, repeated infection and significant increase in serum IgE levels, HIES should be suspected, and genetic screening should be carried out to make definite diagnosis and classification, to achieve better long-term management and improve prognosis.
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Objective@#To study the relationship between STAT3 gene (rs2293152, rs957970) polymorphism and susceptibility to bronchial asthma in children, and to lay the foundation for search of the candidate pathogenic gene of asthma and early prevention of the disease.@*Methods@#One hundred and thirty hospitalized asthmatic children or out-patients with asthma at Affiliated Hospital of Southwest Medical University from September 2013 to September 2017 were selected as asthmatic group, and at the same time 145 healthy children were selected from the Affiliated Hospital of Southwest Medical University as the healthy control group.Apply sequence specific primers-polymerase chain reaction (SSP-PCR) was applied to detect susceptibility single nucleotide polymorphism (SNP) of STAT3 gene (rs2293152, rs9579700). The statistical differences in distribution between genotype and allele were analyzed between the asthma group and the healthy control group.@*Results@#The distribution frequency of CC genotype of rs2293152 in STAT3 gene was significantly higher in the asthmatic group (19.2%)than that in the healthy control group (9.0%) (χ2=6.065, P=0.014). C allele was significantly higher in asthmatic group (41.9% vs.33.8%) (χ2=3.861, P=0.049). There was no significant difference in the distribution of rs957970 in STAT3 gene between the asthma group and the healthy control group.@*Conclusions@#The SNP of rs2293152 in STAT3 gene is associated with susceptibility to asthma in children in South Sichuan.C allele may be the susceptible gene for childhood asthma, while the SNP of rs957970 in STAT3 gene has no significant correlation with childhood asthma in Southern Sichuan.
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Hyper-immunoglobulin syndrome (HIES) is a multisystem disorder characterized by eczema,skin abscesses,recurrent staphylococcal infections of the skin and lungs,pneumatocele formation,candidiasis,cosinophilia,and elevated serum levels of IgE.The number of helper T lymphocyte 17 cells is reduced or absent,and dominant-negative heterozygous mutation in STAT3 gene are helpful for the diagnosis of the disease.The use of prophylactic antibiotics is a necessary measure to prevent suppurative pneumonia,pulmonary cystic cavity formation and bronchiectasis.
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Objective To investigate the association between single nucleotide polymorphism (SNPs) (rs1053005 and rs744166) and expression level of STAT3 gene and the susceptibility to acute lymphoblastic leukemia (ALL) in Chinese children.Methods A case-control study was performed,and 184 children with ALL and 377 healthy children as controls were recruited.The genotypes of 2 SNPs were detected by using polymerase chain reaction-restriction fragment length polymorphism method.And the expression level of STAT3 gene was detected by using real-time PCR;All the data were analyzed by using SPSS 16.0 software.Results (1) In this study,the genotypes (GG,AG,AA) of rs1053005 had a significant difference between the ALL group and control group (x2 =6.737,P =0.034).Compared with control group,the A allele had a higher frequency in ALL group and A allele was a risk factor(x2 =5.853,P =0.016).But,there was no difference in frequency of genotype rs744166 between the 2 groups (x2 =1.866,P =0.393).(2) There was no significant association between genotypes and risk degree among 3 groups (high risk group,medial risk group and standard risk group) (x2 =0.335,P =0.987).(3) The expression level of STAT3 gene in patients with AA genotype was lower than that of the patients with GG genotype (t =4.758,P =0.009);and compared with patients of the standard risk group,high risk patients had a lower expression level of STAT3 gene (t =5.284,P =0.007).Conclusions The polymorphism of SNP rs1053005 was associated with ALL,with A allele being a risk factor;and the expression level of STAT3 gene maybe associated with the risk degree in ALL patients.
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Objective To investigate the effect and mechanism of RNAi-mediated STAT3 gene silencing on epithelial-to-mesenchymal transition (EMT) of human pancreatic cancer cells.Methods Lentivirus vector mediating RNA interference targeting STAT3 was constructed in SW1990 cell line.The invasion ability of SW1990 cells was determined by cell invasion assay in vitro.Cell proliferation and cell cycle of SW1990 cells were also detected.The expression of EMT related genes such as STAT3,P-STAT3,Twist,Snail and E-cadherin were analyzed by reverse transcription-PCR,real-time PCR,and Western blotting.Results Silencing of STAT3 with RNAi not only markedly reduced proliferation but also greatly decreased the invasion ability of SW1990 cells.The mRNA level and protein expression of Snail decreased significantly (P ＜ 0.05),but those of E-cadherin increased significantly (P ＜ 0.05),compared to parental cells.However,no difference was on the expression of Twist in SW1990 cell line.Conclusions STAT3 signaling pathway plays an important role in the process of EMT.Silencing of STAT3 with RNAi can significantly inhibit EMT by downregulating expression of Snail and E-cadherin in pancreatic cancer cells.
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Objective To explore the effects of X-ray irradiation combined with RNAi against signal transducer and activator of transcription 3(STAT3)on the radiosensitivity of human esophageal carcinoma cells.Methods Human esophageal carcinoma cells of the line Eca-109 were euhured.Three pairs of DNA template aiming at the base sequences of the coding regions 2037-2055,1243-1261,and 455-473 of the STAT3 mRNA were synthesized(siRNAI,siRNA2,and siRNA3),and a negative sequence was synthesized to be used as control.STAT3-siRNA positive recombinant plasmids(pRNAT-U6.1-siRNAI,pRNAT-U6.1-siRNA2, and pRNAT-U6.1-siRNA3), and a STAT3-siRNA negative recombinant plasmid (pRNAT-U6.1-negative)were thus constructed and then transfected into the cultured Eca-109 cells,which were divided into transfection reagent control group,pRNAT-U6.1-siRNAl-3 transfection groups,and pRNAT-U6.1-negative centrel group.The positive eell clones were screened.RT-PCR and Westem blotting were used to detect the STAT3 mRNA and protein expression.The transfected Eca-109 cells were exposed to 0,2,4,6,and 8 Gy of X-rays,respectively,and the survival fraction of the cells was analyzed by clone formation assay.Flow cytometry was applied to analyze the cycle arrest and cell apoptosis 4 Gy post-irradiation.Results Agarose gel electrophoresis confirmed the successful construction of the plasmid pRNAT-U6.1-siRNA.RT-PCR and Western blotting demonstrated that the mRNA and protein expression levels of STAT3 transfected with sTAT3-siRNA3 were both significanfly lower than those of the control groups.At 2-8 Gy, the survival fractions of the siRNA3 group were aU significantly lowered than those of the control group(t＝-0.228--0.051,P<0.05).Flow cytometry showed that the percentage of the cell cycle G0/G1 phase and the apoptosis rate of the siRNA3 group were both significantly higher than those of the control groups at 4 Gy post-irradiation(t＝-13.137-16.350,P<0.01).Conclusions X-ray irradiation combined with RNAi against sTAT3 could inhibit the proliferation of the human esophageal carcinoma cells,induce cell cycle arrest and apoptosis,improve the radiosensitivity in Eta-109 cells.