| 1. |
- Amu, Sylvie, 1978, et al.
(författare)
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Cytokines in the placenta of Pakistani newborns with and without intrauterine growth retardation
- 2006
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Ingår i: Pediatr Res. ; 59:2, s. 254-8
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Tidskriftsartikel (refereegranskat)abstract
- Although intrauterine growth retardation (IUGR) is a major risk factor for increased neonatal mortality and morbidity, the mechanisms behind it are not clear. We analyzed cytokine gene expression and gene polymorphisms in infants with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55 control mother/infant pairs were studied. mRNA for IL-10, IL-8, TNF-alpha, TGF-beta, IL-6, IL-4, IL-1beta, IL-12, IFN-gamma and GAPDH was quantified with RT-PCR from placenta. Cytokine and cytokine receptor gene polymorphisms for -1087IL10, -308TNFA, -174IL6, +915TGFB1, intron 2 IL1RN, +36TNFR1, 150V IL4RA and -159CD14 were determined from genomic DNA. The serum levels of IL-1beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha and TGF-beta were measured. There was a significant decrease of IL-10 and IL-12, but increase of TGF-beta in the decidua and similarly decrease of IL-10, but increase of TGF-beta in the trophoblasts of the IUGR placentas compared with the non-IUGR placentas. We found significantly lower levels of IL-1beta in serum from the mothers of the IUGR infants and of TGF-beta in serum of the infants with IUGR compared with the non-IUGR infants. We note that the IL-10 mRNA expression in the decidua was down-regulated, but the TGF-beta mRNA up-regulated in IUGR placentas of mothers from a population with multiple risk factors for IUGR. We propose that the low IL-10 in the placenta may be involved in the pathogenesis of IUGR and might possibly be treatable.
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| 2. |
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| 3. |
- Donati, Mauro, 1966, et al.
(författare)
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Association of the -159 CD14 gene polymorphism and lack of association of the -308 TNFA and Q551R IL-4RA polymorphisms with severe chronic periodontitis in Swedish Caucasians.
- 2005
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Ingår i: Journal of clinical periodontology. - 0303-6979. ; 32:5, s. 474-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Severe forms of periodontitis are suggested to have a genetic basis. OBJECTIVE: The aim of the present investigation was to study the association of gene polymorphisms related to some immune regulation components (G-308A TNFA, Q551R IL-4RA and C-159T CD14) with severe chronic periodontitis. MATERIALS AND METHODS: Sixty patients (aged 36-74 years; mean 54.5+/-8.5) with severe and generalized chronic periodontitis were included. The patients exhibited bone loss >50% at all teeth. Thirty-nine periodontally healthy subjects between 35 and 78 years of age (mean 51.0+/-10.9) were recruited as controls. DNA was isolated from peripheral blood cells and genotyping was performed by combination of PCR and restriction endonuclease mapping. RESULTS: While gene polymorphisms for TNFA and IL-4RA did not show any association with severe chronic periodontitis, the analysis of the -159 CD14 gene polymorphism revealed significant differences between test and control groups. The proportion of subjects that exhibited the TT genotype was significantly smaller in the group with severe periodontitis than in periodontal healthy group (p=0.028; Fisher's exact test). The C allele carriage was 90% in the periodontitis group and significantly higher than in the healthy control group (72%). CONCLUSION: It is suggested that the -159 CD14 gene polymorphism is associated with chronic periodontitis in Caucasian subjects of a north European origin.
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| 4. |
- Donati, Mauro, 1966, et al.
(författare)
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Local expression of interleukin-10 and mCD14 in relation to the -1087 IL-10 and -159 CD14 gene polymorphisms in chronic periodontitis.
- 2008
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Ingår i: Journal of periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 79:3, s. 517-24
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between different gene polymorphisms and severe chronic periodontitis have been demonstrated. However, the influence of such genetic variations on the production of related proteins needs to be clarified. The aim of the present investigation was to study the local expression of interleukin (IL)-10 and membrane-bound CD14 (mCD14) in relation to the -1087 IL-10 and -159 CD14 gene polymorphisms in subjects with chronic periodontitis. METHODS: Fifty-three white subjects with generalized and severe chronic periodontitis volunteered. Twenty milliliters of blood was collected by venipuncture from each subject. DNA was isolated, and genotype analysis of the -1087 IL-10 and -159 CD14 gene polymorphisms was performed using polymerase chain reaction and restriction endonuclease mapping techniques. A gingival biopsy from one randomly selected diseased proximal site was also obtained from each subject. The biopsies were embedded, snap frozen, and prepared for immunohistochemical analysis. The inflammatory lesion was identified in the sections, and the proportions of IL-10+ and CD14+ cells were determined. RESULTS: The proportion of IL-10+ cells in the peripheral area of the periodontitis lesions was significantly larger in subjects with the -1087 IL-10 GG genotype than in subjects with the AG or AA genotype. However, the local expression of the mCD14 receptor did not vary between subjects with different -159 CD14 genotypes. CONCLUSIONS: It is suggested that IL-10 expression in chronic periodontitis lesions is associated with a distinct genotype. The observation adds to our understanding of interactions between genetic and environmental factors in the development of human diseases.
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| 5. |
- Gateva, Vesela, et al.
(författare)
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A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:11, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
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| 7. |
- Kastbom, Alf, et al.
(författare)
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Fcγ receptor type IIIA genotype and response to tumor necrosis factor alpha-blocking agents in patients with rheumatoid arthritis
- 2007
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 56:2, s. 448-452
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether a functional single-nucleotide polymorphism in the gene encoding Fc receptor type IIIA (FcRIIIA) correlates with the response to treatment with tumor necrosis factor inhibitors in rheumatoid arthritis (RA). Methods: The study population comprised 282 Swedish patients with RA in whom the therapeutic efficacy of conventional disease-modifying antirheumatic drugs had been insufficient. Infliximab or etanercept treatment was initiated, and patients were evaluated after 3 months, using the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 or the European League Against Rheumatism (EULAR) criteria. The chi-square test was used to compare response rates across FcRIIIA genotypes. Results: No differences in genotype distribution were observed among nonresponders compared with ACR20 responders (P = 0.80), ACR50 responders (P = 0.56), or ACR70 responders (P = 0.91). Similar results were observed when analyzing infliximab and etanercept separately or when using the EULAR response criteria. Conclusion: Unlike the findings of a previous study, the results of the current study suggest that the 158V/F polymorphism of FcRIIIA is very unlikely to influence the clinical efficacy of infliximab or etanercept in patients with RA.
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| 8. |
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| 9. |
- Klareskog, Lars, et al.
(författare)
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Genes, environment and immunity in the development of rheumatoid arthritis
- 2006
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Ingår i: Current Opinion in Immunology. - : Elsevier BV. - 0952-7915 .- 1879-0372. ; 18:6, s. 650-655
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Tidskriftsartikel (refereegranskat)abstract
- The combined role of genes, environment and immunity in the development of rheumatoid arthritis (RA) has been the subject of recent investigations. New data support a gene-environment interaction between smoking and the MHC class II HLA-DRB1 shared epitope (SE) genes in anti-citrulline antibody (anti-CP(+)) RA but not in anti-CP(-) disease. These data from genetic epidemiology, together with information on citrullination in the lungs of smokers, have prompted the formulation of a new etiological hypothesis for anti-CP(+) RA, suggesting that smoking in the context of HLA-DR SE might trigger immunity to citrulline-modified proteins and that this immunity, after several years, might cause arthritis.
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| 10. |
- Klareskog, Lars, et al.
(författare)
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Immunity to Citrullinated Proteins in Rheumatoid Arthritis
- 2008
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Ingår i: Annual Review of Immunology. - : Annual Reviews. - 0732-0582 .- 1545-3278. ; 26, s. 651-675
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Forskningsöversikt (refereegranskat)abstract
- Antibodies to citrullinated proteins (ACPA), i.e., to peptides posttranslationally modified by the conversion of arginine to citrulline, are specific serological markers for rheumatoid arthritis (RA). Studies on anticitrulline immunity, summarized in this review, demonstrate that the criterion-based syndrome RA should be subdivided into at least two distinct subsets (ACPA-positive and ACPA-negative disease). A new etiological model is proposed for ACPA-positive RA, built on MHC class II-dependent activation of adaptive immunity. Fundamentals of this model include the following: (a) ACPA antedate onset of arthritis; (b) ACPA may aggravate arthritis in rodents; (c) ACPA are triggered in the context of genes that confer susceptibility to RA (HLA-DRB1 SE) and by environmental agents triggering RA (smoking or bacterial stimuli); (d) ACPA may complex with citrullinated proteins present in target tissue as part of a multistep process for arthritis development. The model provides a new basis for molecular studies on the pathogenesis of ACPA-positive arthritis.
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