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- Tuyet Vuong, Mai, et al.
(author)
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Genetic evidence for involvement of adaptive immunity in the development of IgA nephropathy: MHC class II alleles are protective in a Caucasian population
- 2013
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In: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 74:8, s. 957-960
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Journal article (peer-reviewed)abstract
- There is evidence suggesting that IgA nephropathy (IgAN) is an immunological disease. The role of FILA class II DR beta 1 (DRB1) has previously not been well studied. The aim of our study was to investigate the association of HLA-DRB1 variants with IgAN in a Swedish Caucasian cohort. Our study consisted of 213 patients with biopsy proven IgAN, all of self-reported Caucasian ancestry. As a control cohort, 1569 healthy subjects from the same population in Sweden were included. HLA-DRB1 low-resolution genotyping was performed and odds ratios were calculated to assess the risk. less thanbrgreater than less thanbrgreater thanIn an allelic model the HLA-DRB1*03 and *10, demonstrated association for IgAN after correction for multiple comparison, with subsequent OR = 0.54 (95% CI 0.37-0.78) and 3.44 (95% Cl 1.67-7.07). When the influence of risk allelic groups was adjusted for protective allelic groups and vice versa, only a protective effect of HLA-DRB1*03 remained significant. less thanbrgreater than less thanbrgreater thanIn conclusion, the variants of HLA-DRB1 were associated with IgAN of which the HLA-DRB1*03 revealed a strong protective effect for IgAN. Our data replicates finding from other Caucasian populations and suggest that involvement of adaptive immunity may be of importance in the development of the disease.
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| 4. |
- Tuyet Vuong, Mai, et al.
(author)
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Genetic Risk Factors in Lupus Nephritis and IgA Nephropathy - No Support of an Overlap
- 2010
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:5
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Journal article (peer-reviewed)abstract
- Background: IgA nephropathy (IgAN) and nephritis in Systemic Lupus Erythematosus (SLE) are two common forms of glomerulonephritis in which genetic findings are of importance for disease development. We have recently reported an association of IgAN with variants of TGFB1. In several autoimmune diseases, particularly in SLE, IRF5, STAT4 genes and TRAF1-C5 locus have been shown to be important candidate genes. The aim of this study was to compare genetic variants from the TGFB1, IRF5, STAT4 genes and TRAF1-C5 locus with susceptibility to IgAN and lupus nephritis in two Swedish cohorts. Patients and Methods: We genotyped 13 single nucleotide polymorphisms (SNPs) in four genetic loci in 1252 DNA samples from patients with biopsy proven IgAN or with SLE (with and without nephritis) and healthy age-and sex-matched controls from the same population in Sweden. Results: Genotype and allelic frequencies for SNPs from selected genes did not differ significantly between lupus nephritis patients and SLE patients without nephritis. In addition, haplotype analysis for seven selected SNPs did not reveal a difference for the SLE patient groups with and without nephritis. Moreover, none of these SPNs showed a significant difference between IgAN patients and healthy controls. IRF5 and STAT4 variants remained significantly different between SLE cases and healthy controls. In addition, the data did not show an association of TRAF1-C5 polymorphism with susceptibility to SLE in this Swedish population. Conclusion: Our data do not support an overlap in genetic susceptibility between patients with IgAN or SLE and reveal no specific importance of SLE associated SNPs for the presence of lupus nephritis.
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- Vuong, Mai T, et al.
(author)
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Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy
- 2010
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In: KIDNEY INTERNATIONAL. - : Nature Publishing Group. - 0085-2538 .- 1523-1755. ; 78:12, s. 1281-1287
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Journal article (peer-reviewed)abstract
- The Fc-alpha receptor (Fc alpha R/CD89) is involved in IgA complex formation and may affect the development of IgA nephropathy (IgAN). In this study, we tested the genetic variations of the CD89 gene in relation to disease susceptibility in IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and in controls. There was a significant difference between the levels of sCD89-IgA complexes, measured by sandwich enzyme-linked immunosorbent assay (ELISA), in 177 patients with IgAN with and without disease progression at the time of first diagnosis. No such difference was found in 42 patients with other renal diseases. The patients with IgAN without disease progression had stable but high levels of sCD89 over 5-15 years of follow-up in contrast to stable but low levels of sCD89 in the disease progression group. Moreover, levels of sCD89 complexes were correlated with one of the five CD89 genetic variants in 212 patients with IgAN and 477 healthy Caucasians; the single-nucleotide polymorphism (SNP) rs11084377 was significantly associated with a lower expression of sCD89. However, no association between CD89 gene polymorphisms and susceptibility to IgAN was detected. Thus, we found an association between the levels of sCD89-IgA complexes in serum and the severity of IgAN, and a possible genetic component in regulating the production or expression of sCD89.
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| 7. |
- Vuong, Mai Tuyet
(author)
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Genetic studies of glomerulonephritis with special focus on IgA nephropathy and Lupus nephritis
- 2010
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Doctoral thesis (other academic/artistic)abstract
- IgA nephropathy and nephritis in Systemic Lupus Erythematosus (SLE) are two common forms of glomerulonephritis with unknown etiology. As for many other complex diseases, both genetic and environmental factors could be of importance for disease development. However, immunological and biochemical similarities between SLE and IgA nephropathy demonstrate a direct link to impaired immune function in both diseases. In our study we tested the hypothesis that there is an overlap in genetic susceptibility between Lupus nephritis and IgA nephropathy and we aimed to identify specific biomarkers associated with the severity of nephritis. We addressed this question in cohorts of 212 individuals with IgA nephropathy, 272 individuals with SLE, including 106 with nephritis and up to 1569 individuals from a healthy control population, by analysis of genetic variants in genomic DNA and by investigation of plasma from patients and controls.Our analysis of distribution of HLA-DRB1 variants showed a significant association with IgA nephropathy, with the HLA-DRB1 *03, and *15 revealing a strong protective effect for IgA nephropathy. In contrast, the HLA-DRB1 *03, and *15 indicated a risk effect to SLE. We found a similar contrast in respect to non-HLA risk factors for these two types of nephritis. While TGFB1 gene variants are associated with IgA nephropathy, this was not demonstrated for Lupus nephritis. On the other hand, several genetic polymorphisms previously found in association with SLE, like IRF5, STAT4 and TRAF1-C5, were not demonstrated to associate with Lupus nephritis or with IgA nephropathy in our cohort. Additionally, we found no evidence for an association of FCAR (CD89) gene polymorphisms in the investigated nephritis groups. No genetic factors associated with the progress of IgA nephropathy were detected in these genetic association studies.Two biomarkers were tested in nephritis patients: mannose-binding lectin (MBL) and soluble CD89 receptor (sCD89, Fc alpha receptor). A new method for detection of sCD89-IgA complex in human serum/plasma was developed and applied in the IgA nephropathy cohort. Our study does not suggest that it is possible to predict development of nephritis based on these biomarkers. However, a significant association between low levels (less than 10 relative units) of sCD89-IgA complex in sera of IgA nephropathy patients and disease progression was detected. In a disease control group of patients with other forms of glomerulonephritis, including Lupus nephritis, who had similar renal function and proteinuria as the IgA nephropathy group, no correlation to disease progression was observed. When sCD89 analysis was performed on individuals, with repetitive samples during 5-15 years of follow-up, we found that serum levels of sCD89 remained stable and low in IgA nephropathy patients with disease progression and were continuously high (more than 40 relative units) in IgA nephropathy patients without disease progression. Thus, the sCD89 level could be a valuable prognostic marker of progressive renal failure in IgA nephropathy patients. In our study we identified several genetic factors and a specific biomarker, which are different for IgA nephropathy and Lupus nephritis risk or progression. These findings point to a difference in the possible mechanisms of renal failure and suggest detection of HLADRB1 alleles for differential diagnostics of IgA nephropathy and Lupus nephritis at early stages of the disease. The discovery of a prognostic factor for disease progression in IgA nephropathy suggests that earlier and more aggressive therapy should be instituted, as well as opening the possibility of developing new methods of treatment for severe IgA nephropathy cases.
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| 8. |
- Vuong, Mai Tuyet, et al.
(author)
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Genetic variation in the transforming growth factor-beta1 gene is associated with susceptibility to IgA nephropathy
- 2009
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In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 24:10, s. 3061-7
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Journal article (peer-reviewed)abstract
- BACKGROUND: There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis. METHODS: We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephropathy patients, 146 men and 66 women and 477 healthy age-matched controls (321 men and 156 women) from the same population in Sweden. RESULTS: Frequencies of four out of five selected SNPs (rs6957, rs2241715, rs1800471, rs1982073 and rs1800469) were found to significantly differ between male patients and male controls in a co-dominant model (corrected P
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| 9. |
- Yu, Xianbin, et al.
(author)
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Preface
- 2024
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In: Journal of Physics. - : IOP Publishing.
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Conference paper (peer-reviewed)
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