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| 2. |
- Giha, Hayder A., et al.
(författare)
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Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh
- 2010
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:7, s. 1732-1739
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Tidskriftsartikel (refereegranskat)abstract
- The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained from a cohort of 136 donors from Daraweesh in Sudan. The cohort was followed for malaria infection for 9 years. After an initial analysis, the immune response to Pf332-C231 antigen was the only one found associated with protection, thus taken for further analysis. The number of previous clinical malaria episodes experienced by the donors was used as an index for relative protection. The number of these episodes was found to be negatively correlated with the levels of pre-existing total IgG, IgG2 and IgG3 to Pf332-C231 (correlation coefficient, CC - 0.215, p=0.012; CC - 0.195, p=0.023 and CC - 0.211, p=0.014, respectively), and also with age (CC - 0.311, p<0.001). Unexpectedly, equal levels of Pf332-C231 antibodies were induced by both patent and sub-patent infections regardless of the number of previous malaria episodes (1-7). Combining the correlation analysis with a multi-linear regression, three variable markers for protection were emerged, two age-dependent, the antibody response to Pf332-C231 and an unidentified marker (likely immune response to other antigens), and the third was an age-independent unidentified marker (possibly gene polymorphisms). In conclusion, this report suggests a protective effect for IgG subclasses to Pf332-C231 antigen against malaria.
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| 3. |
- Nasr, Amre, et al.
(författare)
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Fc gamma receptor IIa (CD32) polymorphism and antibody responses to asexual blood-stage antigens of Plasmodium falciparum malaria in Sudanese patients
- 2007
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Ingår i: Scandinavian Journal of Immunology. - Oxford : Blackwell Science. - 0300-9475 .- 1365-3083. ; 66:1, s. 87-96
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Tidskriftsartikel (refereegranskat)abstract
- In a prospective clinical study in New Halfa Teaching Hospital, the possible association between FcRIIa-R/H131 polymorphism and anti-malarial antibody responses with clinical outcome of Plasmodium falciparum malaria among Sudanese patients was investigated. A total of 256 individuals were consecutively enrolled, comprising 115 patients with severe malaria, 85 with mild malaria and 56 malaria-free controls. Genotyping of FcRIIa-R/H131 dimorphism was performed using gene-specific polymerase chain reaction (PCR) amplification with allele-specific restriction enzyme digestion of the PCR product. The antibody responses to asexual blood-stage antigens were assessed by an enzyme-linked immunosorbent assay. The frequency of the FcRIIa-R/R131 genotype was significantly higher in those with severe malaria when compared with patients with mild malaria, while the FcRIIa-H/H131 genotype showed a significant association with mild malaria. A reduced risk of severe malaria with IgG3 antibodies in combination with the H/H131 genotype was observed. Furthermore, low levels of IgG2 antibodies reactive with the Pf332-C231 antigen were also associated with lower risk of severe malaria in individuals carrying the H131 allele. The levels of IgG1 and IgG3 antibodies were statistically significantly higher in the mild malaria patients when compared with the severe malaria patients. Taken together, our study revealed that the FcRIIa-R/R131 genotype is associated with the development of severe malaria, while the H/H131 genotype is more likely to be associated with mild malaria. Our results also revealed that the natural acquisition of immunity against clinical malaria appeared to be more associated with IgG1 and IgG3 antibodies, signifying their roles in parasite-neutralizing immune mechanisms.
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| 4. |
- Giha, Hayder A., et al.
(författare)
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Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria.
- 2009
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined. RESULTS: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent. DISCUSSION: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible CONCLUSIONS: The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.
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| 5. |
- Giha, Hayder A, et al.
(författare)
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Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria
- 2010
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Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1076-1551 .- 1528-3658. ; 16:1-2, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Sudanese donors, followed for malaria infection for 9 years, had their CRP -286 gene locus genotyped by pyrosequencing. The number of malaria episodes experienced by each individual over the study period was used as an index for malaria susceptibility. The prevalence of the CRP alleles A, C and T were 21%, 52% and 27%, respectively. Importantly, the A-allele, unlike the C- and T-alleles or CRP genotypes, was significantly associated with an increased number of malaria episodes, P = 0.007. The proportion of A-allele carriers among donors not known to have had malaria during the study period was 18%, whereas it was 43% and 63% among donors who had experienced 1-4 and > or =5 malaria episodes, respectively, over the same period (P = 0.002). Furthermore, the A-allele was associated with higher parasite counts. In conclusion, the CRP -286 A-allele was associated with an increased susceptibility to uncomplicated Plasmodium falciparum malaria.
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| 6. |
- Giha, Hayder A., et al.
(författare)
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Associations of multi-locus polymorphisms in an immune network with susceptibility to uncomplicated Plasmodium falciparum malaria in Daraweesh village, Eastern Sudan
- 2011
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Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 11:7, s. 1674-1681
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to uncomplicated malaria (UM), as to other forms of the disease, is genetically determined. Over 9-years of clinical and parasitological follow up of inhabitants of Daraweesh, in Eastern Sudan, the relative susceptibility to UM was estimated in terms of number of episodes experienced by each individual. Previously, we reported that the levels of IgG2 and IgG3 to Pf332-C231 malaria antigen are negatively correlated with number of malaria episodes. In addition, four molecular markers for malaria susceptibility (CRP -286, GM/KM haplotypes, FcγRIIa131 and HbAS) were tested. In this study, the above data were combined and reanalysed. The CRP -286A allele and GM 1,17 5,13,14,6 phenotype were previously found to be associated with increased susceptibility to malaria; however, individuals have both polymorphism together were not more susceptible to UM than the non-carriers of the same double polymorphism. The FcγRIIa-RR131 and HbAA genotypes taken individually or as double polymorphism were not associated with malaria susceptibility; however, their combination with any or both of the former polymorphisms was mostly associated with increased susceptibility to malaria. None of the four markers were associated with the levels of IgG2 and IgG3 against Pf332-C231. In conclusion, while our data support the polygenic nature of susceptibility to UM and highlighted the role of immune markers polymorphisms, the combinations of these markers were not predictable, i.e. the combination of the susceptibility markers will not necessarily render the carriers more susceptible to UM.
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| 7. |
- Giha, Hayder A., et al.
(författare)
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Clustering of malaria treatment failure (TF) in Daraweesh : hints for host genetic susceptibility to TF with emphasis on immune-modulating SNPs
- 2010
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Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 10:4, s. 481-6
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Tidskriftsartikel (refereegranskat)abstract
- In malaria, drug resistance and treatment failure (TF) are not synonymous, although are escalating together. Over 9 years of surveillances for malaria morbidity and TF in Daraweesh village in eastern Sudan (1991-2004), 136 donors (15-78 years) from 43 households, treated for 278 malaria episodes and had experienced 46 incident of TF, were included in this study. Blood obtained from the donors in 2005, was used for measurement of IgG subclasses against Pf332-C231 antigen and GM/KM allotyping and for genotyping of the donors for; FcgammaRIIA 131 (HH, RH, RR), CRP 286 (C
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| 8. |
- Giha, Hayder A., et al.
(författare)
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Lack of significant influence for Fc gamma RIIa-RH131 or hemoglobin AA/AS polymorphisms on immunity and susceptibility to uncomplicated malaria and existence of marked linkage between the two polymorphisms in Daraweesh
- 2012
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 14:6, s. 537-544
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Tidskriftsartikel (refereegranskat)abstract
- Malaria signature on human genome is marked by several gene polymorphisms. HemoglobinAS (HbAS) is known to protect against severe malaria, but barely proved to protect against uncomplicated malaria (UM). Similarly, the influence of Fc gamma RIIa-RH131 polymorphism on malaria is controversial. Polymorphisms in both genes were examined and levels of IgG subclasses against four malaria antigens were measured for 250 Fulani's from Daraweesh, eastern Sudan. Morbidity data for up to nine years was available for 214 donors. Number of malaria episodes experienced by each individual during the study period was used as indicator for susceptibility to UM. PCR and RFLP were used for donors DNA genotyping and ELISA for antibodies measurement. Results revealed that neither Fc gamma RIIa-RH131 alleles/genotypes nor HbAA/AS was significantly associated with malaria morbidity or with levels of IgG to test antigens. Both polymorphisms were in Hardy-Weinberg Equilibrium, interestingly, there was strong association between the two polymorphisms (linkage disequilibrium - LD) with D' = 0.89. The association between the two polymorphisms was confirmed by analysis of independent material from a neighboring village. In conclusion, in Daraweesh both Fc gamma RIIa-RH131 and HbAA/AS genotypes, independently or together, were not major markers for UM susceptibility, however, marked LD was observed between the two polymorphisms.
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| 9. |
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| 10. |
- Israelsson, Elisabeth, et al.
(författare)
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Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa
- 2009
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875 .- 1475-2875. ; 8:136
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Tidskriftsartikel (refereegranskat)abstract
- Background C-reactive protein (CRP) is an acute phase protein that can activate various immune cells and bind to certain Fcγ receptors. The latter may compete with the binding of IgG antibodies to these receptors and could thereby interfere with the antigen-specific immune response. Polymorphisms in the promoter region of the CRP gene have been strongly associated with the plasma concentration of CRP. The known lower susceptibility to malaria in the Fulani ethnic group, as compared to their sympatric neighbours in Africa, has been linked to different genetic backgrounds. The present study was performed to investigate if polymorphisms in the CRP gene could contribute to the lower susceptibility to malaria seen in the Fulani ethnic group. Methods The CRP -717 T>C, -286 C>T>A, and +1444 C>T polymorphisms were analysed in asymptomatic Fulani and non-Fulani individuals from Mali and Sudan using Pyrosequencing T and TaqMan r MGB probes. Results The rare -286 A allele, previously shown to be associated with increased CRP expression and plasma levels, was shown to be more frequent in the non-Fulani ethnic groups as compared to the sympatric Fulani ethnic group both in Mali and Sudan. The common -717 T allele was more prevalent in the non-Fulani ethnic group compared to the sympatric Fulani ethnic group, but only in Mali. The parasite prevalence was increased for the -286 A allele, but not for the -717 T allele. No differences regarding genotype frequency or parasite prevalence were seen for +1444 C>T. Conclusion This study indicate that CRP may play an important role in the immune responses to malaria, and that the -286 C/T/A CRP polymorphism may be a contributing factor to the lower susceptibility to malaria seen in the Fulani.
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