Browsing by Author "Kikuchi, M."
Now showing 1 - 6 of 6
Results Per Page
Sort Options
Item Associations between frequencies of a susceptible TNF-α promoter allele and protective α-thalassaemias and malaria parasite incidence in vanuatu.(2005) Ubalee, R.; Tsukahara, T.; Kikuchi, M.; Lum, J.K.; Dzodzomenyo, M.; Kaneko, A.; Hirayama, K.Tumour necrosis factor-alpha (TNF-α) is one of the key cytokines that influence the pathology of microbial infections. The genetic susceptibility to severe forms of falciparum malaria is differentially associated with TNF-α promoter gene polymorphisms (TNFP alleles). In a previous study, we identified a TNFP-allele characterized by a C to T transition at position −857 (TNFP-D allele) as a marker for susceptibility to cerebral malaria in Myanmar. The frequencies of TNFP alleles on six islands of Vanuatu, Melanesia (South-west Pacific) were estimated to investigate whether malaria selection pressure on this susceptibility marker has influenced its prevalence. Within the archipelago of Vanuatu there is a decreasing cline of parasite incidence from North to South. Of the four alleles of the TNFP gene detected in Vanuatu, the TNFP-D allele frequencies were inversely correlated with the parasite incidence of islands; TNFP-D varied from 0.55 on the island with the lowest parasite incidence to 0.26 on the island with the highest parasite incidence (r = −0.855, P = 0.03). We also observed a significant correlation between the frequencies of α-thalassaemia alleles, thought to protect against malaria and parasite incidence in the same populations. These data are consistent with a previously reported correspondence between the frequencies of glucose 6-phosphate dehydrogenase (G6PD) deficiency and parasite incidences on the islands of Vanuatu (Kaneko et al. 1998) and indicate that the degree of malaria endemicity has influenced the allele frequencies of at least three loci that confer both susceptibility (TNFP-D) and protection (α-thalassaemias and G6PD deficiency).Item Elevated IL-17 levels in semi-immune anaemic mice infected with Plasmodium berghei ANKA(BioMed Central Ltd., 2018-04) Helegbe, G.K.; Huy, N.T.; Yanagi, T.; Shuaibu, M.N.; Kikuchi, M.; Cherif, M.S.; Hirayama, K.Background: Alterations in inflammatory cytokines and genetic background of the host contribute to the outcome of malaria infection. Despite the promising protective role of IL-17 in infections, little attention is given to further understand its importance in the pathogenesis of severe malaria anaemia in chronic/endemic situations. The objective of this study, therefore, was to evaluate IL-17 levels in anaemic condition and its association with host genetic factors. Methods: Two mice strains (Balb/c and CBA) were crossed to get the F1 progeny, and were (F1, Balb/c, CBA) taken through 6 cycles of Plasmodium berghei (ANKA strain) infection and chloroquine/pyrimethamine treatment to generate semi-immune status. Cytokine levels and kinetics of antibody production, CD4+CD25+T regulatory cells were evaluated by bead-based multiplex assay kit, ELISA and FACs, respectively. Results: High survival with high Hb loss at significantly low parasitaemia was observed in Balb/c and F1. Furthermore, IgG levels were two times higher in Balb/c, F1 than CBA. While CD4+CD25+ Treg cells were lower in CBA; IL-4, IFN-γ, IL-12α and IL-17 were significantly higher (p < 0.05) in Balb/c, F1. Conclusions: In conclusion, elevated IL-17 levels together with high IL-4, IL-12α and IFN-γ levels may be a marker of protection, and the mechanism may be controlled by host factor (s). Further studies of F2 between the F1 and Balb/c will be informative in evaluating if these genes are segregated or further apart. © 2018 The Author(s).Item Human leukocyte antigen class I polymorphisms influence the mild clinical manifestation of Plasmodium falciparum infection in Ghanaian children(Human Immunology, 2011-10) Yamazaki, A.; Yasunami, M.; Ofori, M.; Horie, H.; Kikuchi, M.; Helegbe, G.; Takaki, A.; Ishii, K.; Omar, A.H.; Akanmori, B.D.; Hirayama, K.A prospective study that included 429 children for active detection of mild malaria was conducted in a coastal region of Ghana to reveal whether the incidence of malaria is affected by human leukocyte antigen (HLA) polymorphism. During 12 months of follow-up, 85 episodes of mild clinical malaria in 74 individuals were observed, and 34 episodes among them were accompanied with significant parasitemia at >5000 infected red blood cells per cubic millimeter. Attributable and relative risks conferred by genetic factors in the HLA region were evaluated by comparison of the incidence in children, stratified by carrier status, of a given allele of HLA-A, -B, -DRB1 and TNFA promoter polymorphism. HLA-B*35:01 reduced the incidence by 0.178 events per person per year (0.060 versus 0.239 for B*35:01-positive and -negative subpopulations, respectively), and a relative risk of 0.25, which remained statistically significant after Bonferroni's correction for multiple testing (p c = 8.2 × 10 -5). Further, HLA-B*35:01 and -B*53:01 exhibited opposite effects on the incidence of malaria with significant parasitemia. When parasite densities in different HLA carriers status were compared, HLA-A*01 conferred an increase in parasite load (p = 6.0 × 10 -7). In addition, we found a novel DRB1 allele that appears to have emerged from DRB1*03:02 by single nucleotide substitution. © 2011 American Society for Histocompatibility and Immunogenetics.Item Immunoproteomics identification of major IgE and IgG4 reactive schistosoma japonicum adult worm antigens using chronically infected human plasma(Tropical Medicine and Health, 2012-09) Boamah, D.; Kikuchi, M.; Huy, N.T.; Okamoto, K.; Chen, H.; Ayi, I.; Boakye, D.A.; Bosompem, K.M.; Hirayama, K.Imminoepidemilogical studies from endemic areas have revealed age-dependent resistance correlation with increased level of IgE and decreased level of IgG4 antibodies in responses to schistosomes' soluble worm antigen. However, there have been limited studies on analyses of major antigens that provoke IgE and IgG4 immune response during chronic stage of schistosomiasis. In this study, for the first time, immunoproteomics approach has been applied to identify S. japonicum worm antigens in liquid fractions that are recognized by IgE and IgG4 antibody using plasma from chronically infected population. ProteomeLabPF 2D fractionated 1-D and 2-D fractions of SWA antigens were screened using pooled high IgE/IgG4 reactive plasma samples by dot-blot technique. In 1-D fractions, IgE isotype was detected by fewer antigenic fractions (43.2%). The most recognized isotype was IgG3 (79.5%) followed by IgG1 (75.0%) and IgG4 (61.4%). Liquid chromatography MS/MS protein sequencing of reactive 2-D fractions revealed 18 proteins that were identified, characterized and gene ontology categories determined. 2-D fractions containing proteins such as zinc finger, RanBP2-type, domain-containing protein were strongly recognized by IgE and moderately by IgG4 whereas fractions containing proteins such as ubiquitinconjugating enzyme and cytosolic II 5'-nucleotidase strongly recognizing by IgG subclasses (IgG1, IgG3 and IgG4) but not IgE. By this study, a simple and reproducible proteomic method has been established to identify major immunoreactive S. japonicum antigens. It is anticipated that this will stimulate further research on the immunogenicity and protective potential of proteins identified as well as discovery of novel compounds that have therapeutic importance.© 2012 by The Japanese Society of Tropical Medicine.Item The rs150311303 polymorphism in FcγRIIa enhances IgG binding capacity(Scandinavian Journal of Immunology, 2012-08) Omar, A.H.; Shibata, H.; Yasunami, M.; Yamazaki, A.; Ofori, M.F.; Akanmori, B.D.; Shuaibu, M.N.; Kikuchi, M.; Hirayama, K.Fc gamma receptor (FcγR) provides an important link between humoral and cellular immune responses. FcγRIIa-H131R polymorphism has been associated with differential binding to IgG subclasses and susceptibility to severe malaria phenotypes among different populations in the malaria endemic world. In this study, the effect of FCGR2A gene polymorphisms on susceptibility to symptomatic malaria among Ghanaian cohort children was investigated. Blood samples from four hundred and 29 (429) healthy Ghanaian children were genotyped for FCGR2A polymorphisms by direct DNA sequencing. Attributable and relative risks to symptomatic malaria were calculated for the polymorphic variants. Two major FCGR2A polymorphisms, rs1801274A/G (FcγRIIa-H131R) and rs150311303 (FcγRIIa-ins170L), were identified in the study population, and assessment of their risks did not show significant association with susceptibility to symptomatic malaria. The functional significance of these polymorphisms was also examined by evaluating their binding abilities to IgG subclasses using flow cytometric analysis of HEK cells transfected with the FcγRIIa haplotype variants. The binding assay revealed the rs150311303, which was observed only among carriers of the FcγRIIa-131RR genotype for the rs1801274 to consistently enhance binding capacities to all IgG subclasses. Thus, of the three FcγRIIa haplotype variants observed in this study population, the FcγRIIa RL haplotype variant was observed to have the highest binding ability to IgG1, IgG3 and IgG4. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.Item Toll-like receptor 9 (TLR9) polymorphism associated with symptomatic malaria: a cohort study(2012-05-17) Omar, A.H.; Yasunami, M.; Yamazaki, A.; Shibata, H.; Ofori, M.F.; Akanmori, B.D.; Shuaibu, M.N.; Kikuchi, M.; Hirayama, K.AbstractBackgroundIn areas mesoendemic for malaria transmission, symptomatic individuals play a significant role as reservoirs for malaria infection. Understanding the pathogenesis of symptomatic malaria is important in devising tools for augmenting malaria control. In this study, the effect of TLR9 polymorphisms on susceptibility to symptomatic malaria was investigated among Ghanaian children.MethodsFour hundred and twenty nine (429) healthy Ghanaian children, aged three to eleven years (3–11 years), were enrolled into a cohort study and actively followed up for symptomatic malaria for one year. Four TLR9 single nucleotide polymorphisms (SNPs) namely: rs187084 (C-1486 T), rs5743836(C-1237 T), rs352139 (G + 1174A) and rs352140 (G + 2848A) were genotyped by direct sequencing, and their attributable and relative risks for symptomatic malaria determined. TLR9 haplotypes were inferred using the PHASE software and analysed for the risk of symptomatic malaria. A luciferase assay was performed to investigate whether the TLR9 haplotypes influence TLR9 promoter activity.ResultsThe rs352139 GG genotype showed a significantly increased relative risk of 4.8 for symptomatic malaria (P = 0.0024) and a higher mean parasitaemia (P = 0.04). Conversely, the rs352140 GG genotype showed a significantly reduced relative risk of 0.34 (P = 0.048). TLR9 haplotypes analyses showed that TTAG haplotype was significantly associated with reduced relative risk of 0.2 for symptomatic malaria (P = 4×10-6) and a lower mean parasitaemia (0.007), while CTGA haplotype had an increased relative risk of 3.3 (P = 0.005). Functional luciferase reporter gene expression assay revealed that the TTA haplotype had a significantly higher promoter activity than the CCG, CTG and TCG haplotypes.ConclusionsTaken together, these findings indicate a significant association of TLR9 gene polymorphisms with symptomatic malaria among Ghanaian children in Dangme-West district.