免疫检查点阻断疗法在多种类型的肿瘤治疗中显示出显著的疗效,但其临床应用仍面临着如免疫应答率低及免疫相关不良事件的挑战。免疫球蛋白超家族成员11(identification of immunoglobulin superfamily11,IGSF11)是一种抑制性免疫检查点...免疫检查点阻断疗法在多种类型的肿瘤治疗中显示出显著的疗效,但其临床应用仍面临着如免疫应答率低及免疫相关不良事件的挑战。免疫球蛋白超家族成员11(identification of immunoglobulin superfamily11,IGSF11)是一种抑制性免疫检查点分子,作为T细胞活化的V型免疫球蛋白结构域抑制因子(V-domain immunoglobulin suppressor of T cell activation,VISTA)的特异性配体,其通过IGSF11/VISTA轴抑制T细胞功能,有潜力成为免疫治疗肿瘤的新靶标。IGSF11广泛表达于多种恶性肿瘤中,其调控机制因肿瘤类型不同而存在差别。已有研究证明阻断IGSF11与VISTA结合或对IGSF11进行特异性抑制,可产生抗肿瘤作用。IGSF11与患者预后密切相关,但其在不同肿瘤中的预后价值不同。本文将对IGSF11的结构特征、表达调控机制、与VISTA的相互作用及其在肿瘤微环境中的作用进行系统概述。展开更多
AIM:To investigate the variation of IGSF3 gene in three families with congenital absence of lacrimal puncta and canaliculi,and to lay a foundation for further research on the pathogenic gene of congenital lacrimal duc...AIM:To investigate the variation of IGSF3 gene in three families with congenital absence of lacrimal puncta and canaliculi,and to lay a foundation for further research on the pathogenic gene of congenital lacrimal duct agenesis.METHODS:The members of the three families were recruited.The ophthalmologic examinations in details,including slit-lamp biomicroscope,intraocular pressure and fundus examination,etc.were carried out.All patients were checked with paracentesis of puncta membrane and lacrimal duct probing,as well as the computed tomographydacryocystography(CT-DCG).Peripheral blood of 14 participants(3 normal)from three families were collected,4 mL each,for genomic DNA extraction,and 11 exon fragments of IGSF3 gene were amplified and sequenced by polymerase chain reaction(PCR)to determine whether there were IGSF3 genetic variation.RESULTS:A total of 14 members from three families were screened for 4 synonymous variants:c.930 C>T(p.Pro366=),c.1359 T>C(p.Ser709=),c.1797 G>A(p.Ser855=),c.1539 G>A(p.Ser769=),and 6 missense variants:c.l507 G>A(p.Gly759 Ser),c.1783 T>C(p.Trp851 Arg),c.1952 G>T(p.Ser 907 lle),c.3120 C>G(p.Asp1040 Glu),c.3123 C>G(p.Asp1041 Glu),c.3139_3140 insGAC(p.Asp1046_Pro1047 insAsp),and the latter three were only found in two patients with absence of lacrimal puncta and canaliculi combined with congenital osseous nasolacrimal canal obstruction from the first family.CONCLUSION:The same IGSF3 gene mutation c.31393140 insGAC is found in the patients with congenital absence of lacrimal puncta and canaliculi combine with osseous nasolacrimal canal obstruction.展开更多
A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal p...A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal peptide, a extracellular region with a single Ig Ⅴ-like domain, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosine-based inhibitory motifs (ITIM), suggesting its inhibitory function. IgSF13 shows significant homology to human CMRF35 and pIgR. IgSF13 gene is mapped to chromosome 17q25.2, very close to that of CMRF35. IgSF13 is preferentially expressed in myelo-monocytic cells, including monocytes, monocyte-derived DC, and monocyte-related cell lines. Upon pervanadate treatment, IgSF13 was hyper-phosphorylated and associated with Src homology-2 domain-containing phosphatases SHP-1 and SHIP, but not SHP-2. The identification of IgSF13 as a novel ITIM-bearing receptor selectively expressed by DC and monocytes suggests that it may be potentially involved in the negative regulation of specific leukocyte population.展开更多
BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism diso...BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism disorders such as diabetes.Through genetic and molecular biological methods,more than 10 KS pathogenic genes have been found.AIM To identify the existing mutation sites of KS with diabetes and reveal the relationship between genotype and phenotype.METHODS We studied KS pathogenesis through high-throughput exome sequencing on four diabetes’patients with KS for screening the potential pathogenic sites and exploring the genotype-phenotype correlation.Clinical data and peripheral blood samples were collected from the patients.White blood cells were separated and genomic DNA was extracted.High-throughput sequencing of all exons in the candidate pathogenic genes of probands was performed,and the results obtained were analyzed.RESULTS Sequencing revealed mutations in the KLB p.T313M,ANOS1 p.C172F,and IGSF10 gene(p.Lys1819Arg and p.Arg1035Thr)at different sites,which may have been associated with disease onset.CONCLUSION The diagnosis of KS is challenging,especially in early puberty,and the clinical manifestations reflect physical delays in development and puberty.Timely diagnosis and treatment can induce puberty,thereby improving sexual,bone,metabolic and mental health.展开更多
文摘免疫检查点阻断疗法在多种类型的肿瘤治疗中显示出显著的疗效,但其临床应用仍面临着如免疫应答率低及免疫相关不良事件的挑战。免疫球蛋白超家族成员11(identification of immunoglobulin superfamily11,IGSF11)是一种抑制性免疫检查点分子,作为T细胞活化的V型免疫球蛋白结构域抑制因子(V-domain immunoglobulin suppressor of T cell activation,VISTA)的特异性配体,其通过IGSF11/VISTA轴抑制T细胞功能,有潜力成为免疫治疗肿瘤的新靶标。IGSF11广泛表达于多种恶性肿瘤中,其调控机制因肿瘤类型不同而存在差别。已有研究证明阻断IGSF11与VISTA结合或对IGSF11进行特异性抑制,可产生抗肿瘤作用。IGSF11与患者预后密切相关,但其在不同肿瘤中的预后价值不同。本文将对IGSF11的结构特征、表达调控机制、与VISTA的相互作用及其在肿瘤微环境中的作用进行系统概述。
基金Supported by High-Level Talents Training Foundation of the Armed Police Force(No.GCCRC-02)。
文摘AIM:To investigate the variation of IGSF3 gene in three families with congenital absence of lacrimal puncta and canaliculi,and to lay a foundation for further research on the pathogenic gene of congenital lacrimal duct agenesis.METHODS:The members of the three families were recruited.The ophthalmologic examinations in details,including slit-lamp biomicroscope,intraocular pressure and fundus examination,etc.were carried out.All patients were checked with paracentesis of puncta membrane and lacrimal duct probing,as well as the computed tomographydacryocystography(CT-DCG).Peripheral blood of 14 participants(3 normal)from three families were collected,4 mL each,for genomic DNA extraction,and 11 exon fragments of IGSF3 gene were amplified and sequenced by polymerase chain reaction(PCR)to determine whether there were IGSF3 genetic variation.RESULTS:A total of 14 members from three families were screened for 4 synonymous variants:c.930 C>T(p.Pro366=),c.1359 T>C(p.Ser709=),c.1797 G>A(p.Ser855=),c.1539 G>A(p.Ser769=),and 6 missense variants:c.l507 G>A(p.Gly759 Ser),c.1783 T>C(p.Trp851 Arg),c.1952 G>T(p.Ser 907 lle),c.3120 C>G(p.Asp1040 Glu),c.3123 C>G(p.Asp1041 Glu),c.3139_3140 insGAC(p.Asp1046_Pro1047 insAsp),and the latter three were only found in two patients with absence of lacrimal puncta and canaliculi combined with congenital osseous nasolacrimal canal obstruction from the first family.CONCLUSION:The same IGSF3 gene mutation c.31393140 insGAC is found in the patients with congenital absence of lacrimal puncta and canaliculi combine with osseous nasolacrimal canal obstruction.
文摘A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal peptide, a extracellular region with a single Ig Ⅴ-like domain, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosine-based inhibitory motifs (ITIM), suggesting its inhibitory function. IgSF13 shows significant homology to human CMRF35 and pIgR. IgSF13 gene is mapped to chromosome 17q25.2, very close to that of CMRF35. IgSF13 is preferentially expressed in myelo-monocytic cells, including monocytes, monocyte-derived DC, and monocyte-related cell lines. Upon pervanadate treatment, IgSF13 was hyper-phosphorylated and associated with Src homology-2 domain-containing phosphatases SHP-1 and SHIP, but not SHP-2. The identification of IgSF13 as a novel ITIM-bearing receptor selectively expressed by DC and monocytes suggests that it may be potentially involved in the negative regulation of specific leukocyte population.
文摘BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism disorders such as diabetes.Through genetic and molecular biological methods,more than 10 KS pathogenic genes have been found.AIM To identify the existing mutation sites of KS with diabetes and reveal the relationship between genotype and phenotype.METHODS We studied KS pathogenesis through high-throughput exome sequencing on four diabetes’patients with KS for screening the potential pathogenic sites and exploring the genotype-phenotype correlation.Clinical data and peripheral blood samples were collected from the patients.White blood cells were separated and genomic DNA was extracted.High-throughput sequencing of all exons in the candidate pathogenic genes of probands was performed,and the results obtained were analyzed.RESULTS Sequencing revealed mutations in the KLB p.T313M,ANOS1 p.C172F,and IGSF10 gene(p.Lys1819Arg and p.Arg1035Thr)at different sites,which may have been associated with disease onset.CONCLUSION The diagnosis of KS is challenging,especially in early puberty,and the clinical manifestations reflect physical delays in development and puberty.Timely diagnosis and treatment can induce puberty,thereby improving sexual,bone,metabolic and mental health.
