Objective:To compare the genotype frequencies of HLA class-ⅡDRB1 alleles in Giardia(G.)lamblia-infected children.Methods:A total of 490 Egyptian children aged 2-16 years were subjected to microscopic stool examinatio...Objective:To compare the genotype frequencies of HLA class-ⅡDRB1 alleles in Giardia(G.)lamblia-infected children.Methods:A total of 490 Egyptian children aged 2-16 years were subjected to microscopic stool examination to detect G.lamblia infection,and to exclude other intestinal pathogens.On the basis of their microscopic findings,a group of 80 children were chosen as giardiasis cases,another 80 children were confirmed as Giardia free control group by immunochromatographic test,and the remaining children were excluded.Both giardiasis and control groups were then subjected to blood examination to identify their genetic type of HLA-DRB1 alleles.Results:HLA class-ⅡDRB1*03:01 and DRB1*13:01 alleles were significantly associated with G.lamblia infection(P<0.001 for each variable).On the other hand,HLA class-ⅡDRB1*04:02,DRB1*10:01,DRB1*14:01 and DRB1*15:01 alleles were significantly demonstrated in Giardia free children.However,other HLA-DRB1 alleles did not show any significant association with giardiasis.Conclusions:HLA class-ⅡDRB1*03,DRB1*13,DRB1*04,DRB1*10,DRB1*14 and DRB1*15 alleles may be involved in the establishment of host immune response to G.lamblia infection.展开更多
AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 virus.METHODS: This prospective study was c...AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 virus.METHODS: This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c(BDCA1)+ DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus(HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time PCR.RESULTS: Non-responders [sustained virological response(SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1(6-fold) and negative regulators of JAK-STAT pathway such as SOCS(6-fold) as compared to responders(SVR+ve) to antiviral therapy. The downregulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex(MHC) Class-Ⅱ family as HLA-DP, HLA-DQ(2-fold) and superoxide dismutase(2-fold). Cells grown in the presence of HCV viral proteins had genes downregulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors(4-fold) were upregulated as compared to cells grown in absence of viral proteins.CONCLUSION: Underexpressed MHC class-Ⅱ genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs.展开更多
文摘Objective:To compare the genotype frequencies of HLA class-ⅡDRB1 alleles in Giardia(G.)lamblia-infected children.Methods:A total of 490 Egyptian children aged 2-16 years were subjected to microscopic stool examination to detect G.lamblia infection,and to exclude other intestinal pathogens.On the basis of their microscopic findings,a group of 80 children were chosen as giardiasis cases,another 80 children were confirmed as Giardia free control group by immunochromatographic test,and the remaining children were excluded.Both giardiasis and control groups were then subjected to blood examination to identify their genetic type of HLA-DRB1 alleles.Results:HLA class-ⅡDRB1*03:01 and DRB1*13:01 alleles were significantly associated with G.lamblia infection(P<0.001 for each variable).On the other hand,HLA class-ⅡDRB1*04:02,DRB1*10:01,DRB1*14:01 and DRB1*15:01 alleles were significantly demonstrated in Giardia free children.However,other HLA-DRB1 alleles did not show any significant association with giardiasis.Conclusions:HLA class-ⅡDRB1*03,DRB1*13,DRB1*04,DRB1*10,DRB1*14 and DRB1*15 alleles may be involved in the establishment of host immune response to G.lamblia infection.
基金Supported by Council of Scientific and Industrial Research,No.27(0262)12/EMR-II
文摘AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 virus.METHODS: This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c(BDCA1)+ DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus(HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time PCR.RESULTS: Non-responders [sustained virological response(SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1(6-fold) and negative regulators of JAK-STAT pathway such as SOCS(6-fold) as compared to responders(SVR+ve) to antiviral therapy. The downregulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex(MHC) Class-Ⅱ family as HLA-DP, HLA-DQ(2-fold) and superoxide dismutase(2-fold). Cells grown in the presence of HCV viral proteins had genes downregulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors(4-fold) were upregulated as compared to cells grown in absence of viral proteins.CONCLUSION: Underexpressed MHC class-Ⅱ genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs.
