BACKGROUND A leukocyte adhesion defect(LAD) is a rare primary immunodeficiency disorder. LAD type 1(LAD-1) is the most common, which is caused by ITGB2 mutation resulting in dysfunction of β2 integrin, which impairs ...BACKGROUND A leukocyte adhesion defect(LAD) is a rare primary immunodeficiency disorder. LAD type 1(LAD-1) is the most common, which is caused by ITGB2 mutation resulting in dysfunction of β2 integrin, which impairs leukocyte adherence to the endothelium.CASE SUMMARY The first two cases of LAD-1 in Thailand presented with recurrent omphalitis, soft tissue infection, marked leukocytosis, and neutrophilia. One patient experienced delayed umbilical cord separation. Mutation analysis was performed by direct DNA sequencing of the ITGB2 gene. The results revealed two novel homozygous missense mutations, c.920C>T(p.Leu307Pro) in exon 8 and c.758G>A(p.Arg-253His) in exon 7, and one novel homozygous nonsense mutation, c.262C>T(p.Gln88Ter) in exon 4, in the genomic DNA of the first and second patients, respectively. Heterozygous mutations were identified in the parents of both patients, suggesting a carrier status. The patients were administered intravenous antibiotics for infections with good clinical responses. Hematopoietic stem cell transplantation could not be performed due to the unavailability of matched donors. However, a significant decline in infections was observed after antibiotic prophylaxis. Several follow-up visits were conducted for both patients. They are currently 6 years old.CONCLUSION Molecular analysis is essential for definitive diagnosis, early treatment implementation, and prevention of LAD-1 in future pregnancy.展开更多
Leukocyte adhesion deficiency （LAD） I is a disorder caused due to mutations in a gene （ITGB2） located on chromosome 21 and encodes the β2 subunit of the leukocyte integrin molecules. This leads to defects in the ...Leukocyte adhesion deficiency （LAD） I is a disorder caused due to mutations in a gene （ITGB2） located on chromosome 21 and encodes the β2 subunit of the leukocyte integrin molecules. This leads to defects in the adhesion of leukocytes on endothelial cells which further leads to recurrent microbial infections due to a decrease in the immune response. Base Excision Repair Mechanism （BER） is instrumental in repairing damaged DNA by removing mutated/ damaged bases. We have proposed a hypothesis for the treatment of LAD I by making use of the proteins/enzyme complexes responsible for base excision repair mechanism be introduced into the leukocytes via liposomes. This will target the mutated gene in the leukocytes （mostly neutrophils） and DNA repair will occur. The liposomes can be introduced into the patients via intravenous methods.展开更多
In the search for a therapeutic schedule for spinal cord injury,it is necessary to understand key genes and their corresponding regulatory networks involved in the spinal cord injury process.However,ad hoc selection a...In the search for a therapeutic schedule for spinal cord injury,it is necessary to understand key genes and their corresponding regulatory networks involved in the spinal cord injury process.However,ad hoc selection and analysis of one or two genes cannot fully reveal the complex molecular biological mechanisms of spinal cord injury.The emergence of second-generation sequencing technology(RNA sequencing)has provided a better method.In this study,RNA sequencing technology was used to analyze differentially expressed genes at different time points after spinal cord injury in rat models established by contusion of the eighth thoracic segment.The numbers of genes that changed significantly were 944,1362 and 1421 at 1,4 and 7 days after spinal cord injury respectively.After gene ontology analysis and temporal expression analysis of the differentially expressed genes,C5ar1,Socs3 and CCL6 genes were then selected and identified by real-time polymerase chain reaction and western blot assay.The mRNA expression trends of C5ar1,Socs3 and CCL6 genes were consistent with the RNA sequencing results.Further verification and analysis of C5ar1 indicate that the level of protein expression of C5ar1 was consistent with its nucleic acid level after spinal cord injury.C5ar1 was mainly expressed in neurons and astrocytes.Finally,the gene Itgb2,which may be related to C5ar1,was found by Chilibot database and literature search.Immunofluorescence histochemical results showed that the expression of Itgb2 was highly consistent with that of C5ar1.Itgb2 was expressed in astrocytes.RNA sequencing technology can screen differentially expressed genes at different time points after spinal cord injury.Through analysis and verification,genes strongly associated with spinal cord injury can be screened.This can provide experimental data for further determining the molecular mechanism of spinal cord injury,and also provide possible targets for the treatment of spinal cord injury.This study was approved ethically by the Laboratory Animal Ethics Committee of Jiangsu Province,China(approval No.2018-0306-001)on March 6,2018.展开更多
白细胞黏附分子缺陷症Ⅰ型(leukocyte adhesion deficiency type I,LAD-1)是由ITGB2基因突变导致的白细胞黏附功能缺乏的一种原发免疫缺陷病。发病机制是白细胞表面β2整合素表达缺陷和(或)功能异常,导致白细胞不能募集、迁移至炎症或...白细胞黏附分子缺陷症Ⅰ型(leukocyte adhesion deficiency type I,LAD-1)是由ITGB2基因突变导致的白细胞黏附功能缺乏的一种原发免疫缺陷病。发病机制是白细胞表面β2整合素表达缺陷和(或)功能异常,导致白细胞不能募集、迁移至炎症或感染部位发挥作用。不同部位反复感染是该病的主要临床表现,其中以皮肤黏膜及软组织为著,并常伴有脐带延迟脱落及白细胞异常升高,其伤口常迁延不愈,不易局限形成脓液。本文将针对该病的发病机制展开综述,以期提高儿科临床医师对该病的认知,为临床诊疗提供参考依据。展开更多
基金supported by Phramongkutklao College of Medicine
文摘BACKGROUND A leukocyte adhesion defect(LAD) is a rare primary immunodeficiency disorder. LAD type 1(LAD-1) is the most common, which is caused by ITGB2 mutation resulting in dysfunction of β2 integrin, which impairs leukocyte adherence to the endothelium.CASE SUMMARY The first two cases of LAD-1 in Thailand presented with recurrent omphalitis, soft tissue infection, marked leukocytosis, and neutrophilia. One patient experienced delayed umbilical cord separation. Mutation analysis was performed by direct DNA sequencing of the ITGB2 gene. The results revealed two novel homozygous missense mutations, c.920C>T(p.Leu307Pro) in exon 8 and c.758G>A(p.Arg-253His) in exon 7, and one novel homozygous nonsense mutation, c.262C>T(p.Gln88Ter) in exon 4, in the genomic DNA of the first and second patients, respectively. Heterozygous mutations were identified in the parents of both patients, suggesting a carrier status. The patients were administered intravenous antibiotics for infections with good clinical responses. Hematopoietic stem cell transplantation could not be performed due to the unavailability of matched donors. However, a significant decline in infections was observed after antibiotic prophylaxis. Several follow-up visits were conducted for both patients. They are currently 6 years old.CONCLUSION Molecular analysis is essential for definitive diagnosis, early treatment implementation, and prevention of LAD-1 in future pregnancy.
文摘Leukocyte adhesion deficiency （LAD） I is a disorder caused due to mutations in a gene （ITGB2） located on chromosome 21 and encodes the β2 subunit of the leukocyte integrin molecules. This leads to defects in the adhesion of leukocytes on endothelial cells which further leads to recurrent microbial infections due to a decrease in the immune response. Base Excision Repair Mechanism （BER） is instrumental in repairing damaged DNA by removing mutated/ damaged bases. We have proposed a hypothesis for the treatment of LAD I by making use of the proteins/enzyme complexes responsible for base excision repair mechanism be introduced into the leukocytes via liposomes. This will target the mutated gene in the leukocytes （mostly neutrophils） and DNA repair will occur. The liposomes can be introduced into the patients via intravenous methods.
基金supported by the National Natural Science Foundation of China,No.31570983(to XDW)the Priority Academic Program Development of Jiangsu Higher Education Institutes of China
文摘In the search for a therapeutic schedule for spinal cord injury,it is necessary to understand key genes and their corresponding regulatory networks involved in the spinal cord injury process.However,ad hoc selection and analysis of one or two genes cannot fully reveal the complex molecular biological mechanisms of spinal cord injury.The emergence of second-generation sequencing technology(RNA sequencing)has provided a better method.In this study,RNA sequencing technology was used to analyze differentially expressed genes at different time points after spinal cord injury in rat models established by contusion of the eighth thoracic segment.The numbers of genes that changed significantly were 944,1362 and 1421 at 1,4 and 7 days after spinal cord injury respectively.After gene ontology analysis and temporal expression analysis of the differentially expressed genes,C5ar1,Socs3 and CCL6 genes were then selected and identified by real-time polymerase chain reaction and western blot assay.The mRNA expression trends of C5ar1,Socs3 and CCL6 genes were consistent with the RNA sequencing results.Further verification and analysis of C5ar1 indicate that the level of protein expression of C5ar1 was consistent with its nucleic acid level after spinal cord injury.C5ar1 was mainly expressed in neurons and astrocytes.Finally,the gene Itgb2,which may be related to C5ar1,was found by Chilibot database and literature search.Immunofluorescence histochemical results showed that the expression of Itgb2 was highly consistent with that of C5ar1.Itgb2 was expressed in astrocytes.RNA sequencing technology can screen differentially expressed genes at different time points after spinal cord injury.Through analysis and verification,genes strongly associated with spinal cord injury can be screened.This can provide experimental data for further determining the molecular mechanism of spinal cord injury,and also provide possible targets for the treatment of spinal cord injury.This study was approved ethically by the Laboratory Animal Ethics Committee of Jiangsu Province,China(approval No.2018-0306-001)on March 6,2018.
文摘白细胞黏附分子缺陷症Ⅰ型(leukocyte adhesion deficiency type I,LAD-1)是由ITGB2基因突变导致的白细胞黏附功能缺乏的一种原发免疫缺陷病。发病机制是白细胞表面β2整合素表达缺陷和(或)功能异常,导致白细胞不能募集、迁移至炎症或感染部位发挥作用。不同部位反复感染是该病的主要临床表现,其中以皮肤黏膜及软组织为著,并常伴有脐带延迟脱落及白细胞异常升高,其伤口常迁延不愈,不易局限形成脓液。本文将针对该病的发病机制展开综述,以期提高儿科临床医师对该病的认知,为临床诊疗提供参考依据。
