高IgE综合征(hyper-IgE syndrome,HIES)是一类罕见且复杂的原发性免疫缺陷病,包括常染色体显性遗传HIES(autosomal-dominant hyper immunoglobulin E syndrome,AD-HIES)和常染色体隐性HIES(autosomal-recessive hyper immunoglobulin E ...高IgE综合征(hyper-IgE syndrome,HIES)是一类罕见且复杂的原发性免疫缺陷病,包括常染色体显性遗传HIES(autosomal-dominant hyper immunoglobulin E syndrome,AD-HIES)和常染色体隐性HIES(autosomal-recessive hyper immunoglobulin E syndrome,AR-HIES)[1]。HIES发病率极低,临床表现多样且临床医生对该病普遍缺少认识,极易误诊[2]。本文通过报道1例在我院诊断的由DOCK8基因变异导致的AR-HIES病例及相关文献复习,以提高对该病的认识。展开更多
Genetic mutations in the gene encoding DOCK8 cause an autosomal recessive form of hyper immunoglobulin E syndrome （AR-HIES）, referred to as DOCK8 deficiency. DOCK8 deficiency in humans results in the onset of combin...Genetic mutations in the gene encoding DOCK8 cause an autosomal recessive form of hyper immunoglobulin E syndrome （AR-HIES）, referred to as DOCK8 deficiency. DOCK8 deficiency in humans results in the onset of combined immunodeficiency disease （CID）, clinically associated with chronic infections with diverse microbial pathogens, and a predisposition to malignancy. It is now becoming clear that DOCK8 regulates the function of diverse immune cell sub-types, particularly lymphocytes, to drive both innate and adaptive immune responses. Early studies demonstrated that DOCK8 is required for lymphocyte survival, migration and immune synapse formation, which translates to poor pathogen control in the absence of DOCK8. However, more recent advances have pointed to a crucial role for DOCK8 in regulating the signal transduction events that control transcriptional activity, cytokine production and functional polarization of immune cells. Here, we summarize recent advances in our understanding of DOCK8 function, paying particular attention to an emerging role as a signaling intermediate to promote immune responses to diverse external stimuli.展开更多
高IgE综合征又称为Job综合征，分为常染色体显性遗传高IgE综合征（AD-HIES）和常染色体隐性遗传高IgE综合征（AR-HIES）。常染色体显性遗传HIES（autosomal dominant high immunoglobulin E syndrome，AD-HIES）是信号转导和转录激活因...高IgE综合征又称为Job综合征，分为常染色体显性遗传高IgE综合征（AD-HIES）和常染色体隐性遗传高IgE综合征（AR-HIES）。常染色体显性遗传HIES（autosomal dominant high immunoglobulin E syndrome，AD-HIES）是信号转导和转录激活因子3（signal transducer and activator of transcription 3，STAT3）基因显性负突变引起，而常染色体隐性遗传HIES（autosomal recessive high Immunoglobulin E syndrome，AR-HIES）一般与细胞质分裂因子8（dedicator of cytokinesis 8，DOCK8）和非受体酪氨酸蛋白激酶2（tyrosine kinase 2，TYK2）突变密切相关。展开更多
Some patients with chronic hepatitis B virus(HBV)infection failed to clear HBV,even persistently continue to produce antibodies to HBV.Here we performed a two stage genome wide association study in a cohort of Chinese...Some patients with chronic hepatitis B virus(HBV)infection failed to clear HBV,even persistently continue to produce antibodies to HBV.Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV.The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive)compared with 102 control patients(antiHBs positive,HBsAg negative).Over 80%of individual sequences displayed 209 sequence coverage.Adapters,uncertain bases[10%or low-quality base calls([50%)were filtered and compared to the human reference genome hg19.In the second stage,579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage.Although there were no significant associated gene variants in the first stage,two significant gene associations were discovered when the two stages were assessed in a combined analysis.One association showed rs506121-“T”allele[within the dedicator of cytokinesis 8(DOCK8)gene]was higher in chronic HBV infection group than that in clearance group(P=0.002,OR=0.77,95%CI[0.65,0.91]).The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9)gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P=0.0003,OR=1.35,95%CI[1.15,1.58]).Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection.展开更多
文摘高IgE综合征(hyper-IgE syndrome,HIES)是一类罕见且复杂的原发性免疫缺陷病,包括常染色体显性遗传HIES(autosomal-dominant hyper immunoglobulin E syndrome,AD-HIES)和常染色体隐性HIES(autosomal-recessive hyper immunoglobulin E syndrome,AR-HIES)[1]。HIES发病率极低,临床表现多样且临床医生对该病普遍缺少认识,极易误诊[2]。本文通过报道1例在我院诊断的由DOCK8基因变异导致的AR-HIES病例及相关文献复习,以提高对该病的认识。
文摘Genetic mutations in the gene encoding DOCK8 cause an autosomal recessive form of hyper immunoglobulin E syndrome （AR-HIES）, referred to as DOCK8 deficiency. DOCK8 deficiency in humans results in the onset of combined immunodeficiency disease （CID）, clinically associated with chronic infections with diverse microbial pathogens, and a predisposition to malignancy. It is now becoming clear that DOCK8 regulates the function of diverse immune cell sub-types, particularly lymphocytes, to drive both innate and adaptive immune responses. Early studies demonstrated that DOCK8 is required for lymphocyte survival, migration and immune synapse formation, which translates to poor pathogen control in the absence of DOCK8. However, more recent advances have pointed to a crucial role for DOCK8 in regulating the signal transduction events that control transcriptional activity, cytokine production and functional polarization of immune cells. Here, we summarize recent advances in our understanding of DOCK8 function, paying particular attention to an emerging role as a signaling intermediate to promote immune responses to diverse external stimuli.
文摘高IgE综合征又称为Job综合征，分为常染色体显性遗传高IgE综合征（AD-HIES）和常染色体隐性遗传高IgE综合征（AR-HIES）。常染色体显性遗传HIES（autosomal dominant high immunoglobulin E syndrome，AD-HIES）是信号转导和转录激活因子3（signal transducer and activator of transcription 3，STAT3）基因显性负突变引起，而常染色体隐性遗传HIES（autosomal recessive high Immunoglobulin E syndrome，AR-HIES）一般与细胞质分裂因子8（dedicator of cytokinesis 8，DOCK8）和非受体酪氨酸蛋白激酶2（tyrosine kinase 2，TYK2）突变密切相关。
基金supported by grant from the International Science&Technology Cooperation Program of China(No.2014DFR31200)the National Infrastructure of Chinese Genetic Resources(YCZYPT[2017]01-6)+1 种基金federal funds from the National Cancer Institute,National Institutes of Health,USA(No.N01-CO12400)the National Natural Science Foundation of China(No.30671855)。
文摘Some patients with chronic hepatitis B virus(HBV)infection failed to clear HBV,even persistently continue to produce antibodies to HBV.Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV.The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive)compared with 102 control patients(antiHBs positive,HBsAg negative).Over 80%of individual sequences displayed 209 sequence coverage.Adapters,uncertain bases[10%or low-quality base calls([50%)were filtered and compared to the human reference genome hg19.In the second stage,579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage.Although there were no significant associated gene variants in the first stage,two significant gene associations were discovered when the two stages were assessed in a combined analysis.One association showed rs506121-“T”allele[within the dedicator of cytokinesis 8(DOCK8)gene]was higher in chronic HBV infection group than that in clearance group(P=0.002,OR=0.77,95%CI[0.65,0.91]).The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9)gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P=0.0003,OR=1.35,95%CI[1.15,1.58]).Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection.
