| 1. |
- Eltayeb-Elsheikh, Nezar, et al.
(författare)
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Association of HLA-DR-DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis
- 2020
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 36:8
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis.Methods: A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package.Results: DRB1*03:01-DQA1*05:01-DQB1*02:01 (32.4%; OR = 3.68; P-c < .0001), DRB1*04:05-DQA1*03:02-DQB1*03:02 (6.6%; OR = 6.76; P-c < .0001), DRB1*04:02-DQA1*03:01-DQB1*03:02 (6.0%; OR = 3.10; P-c = .0194), DRB1*04:01-DQA1*03:01-DQB1*03:02 (3.7%; OR = 4.22; P-c = .0335), and DRB1*04:05-DQA1*03:02-DQB1*02:02 (2.7%; OR = 6.31; P-c = .0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01-DQA1*02:01-DQB1*02:02 (OR = 0.41; P-c = .0001), DRB1*13:01-DQA1*01:03-DQB1*06:03 (OR = 0.05; P-c < .0001), DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.03; P-c < .0001), and DRB1*11:01-DQA1*05:05-DQB1*03:01 (OR = 0.07; P-c = .0291) were significantly decreased. Homozygous DRB1*03:01-DQA1*05:01-DQB1*02:01 genotypes and combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*04:05-DQA1*03:02-DQB1*03:02, DRB1*04:02-DQA1*03:01-DQB1*03:02, and DRB1*04:01-DQA1*03:01-DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*07:01-DQA1*02:01-DQB1*02:02 and DRB1*13:02-DQA1*01:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction.Conclusions: HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians.
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| 2. |
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| 3. |
- Ali, Magdi M. M., et al.
(författare)
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Fc gamma RIIa (CD32) polymorphism and onchocercal skin disease : implications for the development of severe reactive onchodermatitis (ROD)
- 2007
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Ingår i: American Journal of Tropical Medicine and Hygiene. - Lawrence, Kans. : American society of tropical medicine and hygiene. - 0002-9637 .- 1476-1645. ; 77:6, s. 1074-8
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Tidskriftsartikel (refereegranskat)abstract
- The pathologic manifestations of Onchocerca volvulus infection depend on the interplay between the host and the parasite. A genetic single nucleotide polymorphism in the Fc gamma RIIa gene, resulting in arginine (R) or histidine (H) at position 131, affects the binding to the different IgG subclasses and may influence the clinical variations seen in onchocerciasis. This study investigated the relationship between this polymorphism and disease outcome. Fc gamma RIIa genotyping was performed on clinically characterized onchocerciasis patients (N = 100) and healthy controls (N = 74). Fc gamma RIIa genotype R/R131 frequencies were significantly higher among patients with severe dermatopathology (P < 0.001). Increased risk of developing this form was mostly associated with one tribe (Masalit) (OR = 3.2, 95% CI 1-9.9, P = 0.042). The H131 allele was found to be significantly associated with a reduced risk of having the severe form of the disease (adjusted OR = 0.26, 95% CI = 0.13-0.46, P < 0.001). Our findings suggest that the polymorphism influences the clinical outcome of onchocerciasis.
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| 6. |
- de Ståhl, Teresita Díaz, et al.
(författare)
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Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array
- 2008
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 29:3, s. 398-408
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Tidskriftsartikel (refereegranskat)abstract
- To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.
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| 7. |
- Elghazali, Gehad, 1962-
(författare)
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Regulatory immune responses in humans naturally primed to Plasmodium falciparum or vaccinated with tetanum toxoid or purified protein derivative
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is well established that the balance between functionally distinct regulatory CD4+ T cells plays a major role in the development of immunity and/or pathogenesis to many different infections. In spite of the importance of Th lineage commitment in disease, the critical questions how the balance between Th1 and Th2 cells is regulated is largely unresolved. This thesis describes work aimed at assessing CD4+ T cell heterogeneity and how this is regulated in humans naturally primed to P. falciparum malaria or vaccinated with tetanus toxoid or BCG.Different types of antigens have been implicated to be of importance in the polarization of Th1 or Th2 cells. To investigate this, we stimulated peripheral blood mononuclear cells (PBMC) with tetanus toxoid (TT) and the mycobacterial antigen, purified protein derivative (PPD) in vitro and determined the number of IFN-g (Th1 cytokine) and IL-4 (Th2 cytokine) producing cells using the ELISPOT assay. PPD preferentially induced IFN-g and very few IL-4 producing cells, while TT- induced both IL-4 and IFN-g. These differences probably reflect the different types of immune responses the two antigens induce, mycobacteria preferentially a cell-mediated Th1 type of immunity, while immunity to tetanus is an antibody-dependent, Th2 type of response.To investigate the role of Th1 and Th2 cells in the regulation of anti-malarial IgE in individuals living in P.falciparum endemic areas, the number of IL-4 and IFN-g producing cells was correlated to the plasma anti-malarial IgE levels. A negative correlation between the number of IFN-g producing cells and anti-P.falciparum IgE was found. For IL-4 there was a weak positive correlation with anti-malarial IgE levels, suggesting that other cells than T cells can produce IL-4. The anti-malarial IgE levels correlated significantly with an increased ratio of IL-4/IFN-g producing cells. These data suggest a regulatory role for IL-4 in the induction of anti-P.falciparum IgE antibodies.When PBMC from two groups of individuals naturally exposed to P.falciparum, living in two different parts of Africa (Burkina Faso and Tanzania), were stimulated in vitro with P.falciparum antigens, no malaria-specific IL-4 producing cells were detected. The levels of IgE were lower in the Burkina individuals as compared to the Tanzania ones. This might reflect differences in malaria exposure or genetic (ethnic) differences between the two study groups.To study the influence of genetic and/or environmental factors on the development and shaping of the human peripheral T cell repertoire, the T cell receptor (TCR) Vb usage in ten adult monozygous (Mz) and nine dizygous (Dz) twin pairs living in a P.falciparum endemic area in The Gambia was studied. The results revealed that the frequencies of cells expressing particular TCR Vb genes were not influenced by the parasitaemia, indicating that malaria exposure is not a dominating factor in shaping the peripheral TCR repertoire in humans. The mean within-pair difference was significantly lower for the Mz than for the Dz pairs. The mean within-pair difference for a group of MHC-class II identical twin pairs was significantly higher than for the Mz group but similar to that of the Dz as a whole. These data indicate that genetic factors other than MHC class II genes (i.e non-MHC) influence the shaping of the peripheral TCR Vb repertoire in humans.To study whether or not IgE-containing malaria sera have the capacity to induce IL-4 in human basophils, IgE containing sera from malaria immune donors were added to tissue culture plates coated with anti-human IgE antibodies. IgE-anti-IgE complexes induced IL-4 in basophils. Serum depleted of IgE induced significantly less IL-4. These data show that malaria IgE can induce IL-4 production in cells of basophil origin that can subsequently amplify Th2 type of responses.Taken together, our data show the existence of functionally distinct T cells in individuals naturally primed to P.falciparum or vaccinated with TT or BCG.
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| 8. |
- Elshafie, Amir I., et al.
(författare)
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Activity and turnover of eosinophil and neutrophil granulocytes are altered in visceral leishmaniasis
- 2011
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Ingår i: International Journal of Parasitology. - : Elsevier BV. - 0020-7519 .- 1879-0135. ; 41:3-4, s. 463-469
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Tidskriftsartikel (refereegranskat)abstract
- Visceral leishmaniasis (VL) is a health issue in Sudan. Our aim was to investigate the involvement of eosinophils and neutrophils in VL by serum and plasma measurements of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) and some key cytokines and chemokines. Blood was collected from 125 VL patients and 181 healthy Sudanese controls from the same rural area. Results showed reduced eosinophil and neutrophil counts in the VL group (P = 0.0001 and P = 0.002, respectively). Serum-ECP levels were higher in the controls (P < 0.0001), while plasma MPO levels were higher in the VL group (P < 0.0001). Levels of IL-5, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-17 were increased among the VL group (P < 0.0001, P = 0.017 and P = 0.03, respectively), whereas eotaxin and IL-8 levels were reduced (P < 0.0001 and P = 0.002, respectively). Positive correlations were found between IL-8 and ECP/MPO (P < 0.0001). We conclude that eosinophil and neutrophil turnover and activity are increased in subjects in rural areas of Sudan. In VL the turnover was further increased, but the relatively low secretory activity of eosinophils and neutrophils in VL may relate to the reduced production and availability of the chemokines eotaxin and IL-8. The combined assay of ECP and MPO in serum and plasma provides further insight into the mechanisms of eosinophil and neutrophil involvement in disease and constitutes a novel approach to the study of disease processes.
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| 9. |
- ElShafie, Amir Ibrahim, et al.
(författare)
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Cystatin C as a marker of immune complex-associated renal impairment in a sudanese population with visceral leishmaniasis
- 2006
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Ingår i: American Journal of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 75:5, s. 864-868
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Tidskriftsartikel (refereegranskat)abstract
- Renal function was studied in visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) by means of the specific marker cystatin C and related to circulating immune complexes and cytokine production. Forty patients with VL (23 with sub-acute disease and 17 with acute disease), 17 patients with PKDL, and 22 healthy controls were included. Cystatin C, but not creatinine, was significantly raised in VL (P = 0.004). The highest levels of cystatin C were found in those with acute disease (P < 0.0001). In VL, cystatin C levels were positively correlated to circulating immune complexes and production of granulocyte-macrophage colony stimulating factor (GM-CSF), but negatively correlated to aspartate aminotransferase and lactate dehydrogenase. We conclude that cystatin C is a superior marker of glomerular function in leishmaniasis and that immune complex deposition and GM-CSF are two functions that most likely are causally involved in the mechanisms leading to glomerular dysfunction in leishmaniasis.
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