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IgAN Patients (igan + patient)

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Selected Abstracts

Fc, receptor I activation induces leukocyte recruitment and promotes aggravation of glomerulonephritis through the FcR, adaptor

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007
Yutaka Kanamaru
Abstract Myeloid cells bear Fc receptors (FcR) that mediate inflammatory signaling through the ITAM-containing FcR, adaptor. They express FcR,-associated Fc,RI, which modulate either activating or inhibitory signaling depending on the type of ligand interaction. The role of Fc,RI, in disease progression remains unknown, notably in IgA nephropathy (IgAN), one of major causes of end-stage renal disease, in which large amounts of circulating IgA-immune complexes (IC) may mediate receptor activation. To analyze the involvement of Fc,RI activation in glomerulonephritis (GN), we generated Tg mice expressing a mutated, signaling-incompetent, human Fc,RIR209L that cannot associate with FcR,. Like Fc,RIwt -Tg mice, they developed mesangial IgA deposits but not macrophage infiltration. Fc,RI activation in Fc,RIwt, but not in Fc,RIR209L, Tg mice resulted in marked inflammation with severe proteinuria and leukocyte infiltration in spontaneous IgAN or anti-glomerular basement membrane Ab-induced GN models. Receptor triggering of syngenically transferred Fc,RIwt Tg macrophages into non-Tg animals induced their recruitment into injured kidneys during GN development. Fc,RIwt cross-linking on macrophages activated MAP kinases and production of TNF-, and MCP-1. Moreover, IgA-IC from IgAN patients activated Fc,RI and induced TNF-, production. Thus, Fc,RI activation mediates GN progression by initiating a cytokine/chemokine cascade that promotes leukocyte recruitment and kidney damage. [source]

Polymorphism of renin-angiotensin system genes in IgA nephropathy

NEPHROLOGY, Issue 5 2004
KENG-THYE WOO
SUMMARY: Background and Aims: Individuals are prone to disease because of certain disease-susceptible genes. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasians and Japanese patients have reported contradictory results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese subjects to assess their clinical impact. Methods: Genotyping was performed with DNA isolated from peripheral leucocytes, polymerase chain reaction amplification of the polymorphic sequence, restriction enzymes digestion, and separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records. Results: Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar, whereas there was a significant increase in the ACE DD genotype (P < 0.05). When comparing patients with end-stage renal failure (IgAN-ESRF) and those without (IgAN-nonESRF), there was no difference among the three gene polymorphisms. In contrast, there were significant differences in higher male prevalence (P < 0.05), increased serum creatinine at presentation (P < 0.05), more sclerosis (P < 0.01) and higher tubulointerstitial lesion score (P < 0.001) in the IgAN-ESRF group. Conclusion: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in the Chinese population. None are significant for prognosticating ESRF. [source]

T-cell receptor repertoire in IgA nephropathy renal biopsies

NEPHROLOGY, Issue 2002
John F Knight
SUMMARY: Renal biopsies from patients with IgA nephropathy (IgAN) were studied to determine whether the presence of ,, and ,, T cells is correlated with disease progression in IgAN. The ,, and ,, T-cell receptor (TCR) repertoire was further analysed in these renal biopsies. Immunohistochemical staining using mAb (TCR, and TCR,) and molecular studies using reverse transcription,polymerase chain reaction (RT-PCR) with primers specific for TCR families were undertaken. CDR3 length spectratyping and sequencing of TCR chains were used to analyse the diversity of the CDR3 region of these receptors. It was demonstrated that the presence of ,, T cells is associated with progressive IgAN while ,, T cells are found in both stable and progressive disease. Analysis of the TCR variable (V), repertoire showed the preferential use of V,8 with marked similarities in the CDR3 region by some renal infiltrating T cells in the kidney of some IgAN patients, although T cells infiltrating the renal interstitium of patients with IgAN express heterogeneous T cell receptors. The data from analysis of ,, T-cell repertoire showed that ,, T cells infiltrating the kidneys of IgAN patients use a restricted subset of ,, T cells with a feature of recurrent junctional amino acid motifs in V,1 T cells. The results suggest that both ,, and ,, T cells are involved in the progression of IgAN to renal failure and also that there is clonal expansion of individual ,, or ,, T cells in the kidneys of some IgAN patients. The conserved amino acid in the TCR CDR3 region of V,8 and the feature of recurrent junctional amino acid motifs in V,1 T cells may indicate antigen-driven selection. [source]

T-cell receptor repertoire in IgA nephropathy renal biopsies

NEPHROLOGY, Issue 2002
John F KNIGHT
SUMMARY: Renal biopsies from patients with IgA nephropathy (IgAN) were studied to determine whether the presence of ,, and ,, T cells is correlated with disease progression in IgAN. the ,, and ,, T-cell receptor (TCR) repertoire was further analysed in these renal biopsies. Immunohistochemical staining using mAb (TCR, and TCR,) and molecular studies using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for TCR families were undertaken. CDR3 length spectratyping and sequencing of TCR chains were used to analyse the diversity of the CDR3 region of these receptors. It was demonstrated that the presence of ,, T cells is associated with progressive IgAN while ,, T cells are found in both stable and progressive disease. Analysis of the TCR variable (V), repertoire showed the preferential use of V,8 with marked similarities in the CDR3 region by some renal infiltrating T cells in the kidney of some IgAN patients, although T cells infiltrating the renal interstitium of patients with IgAN express heterogeneous T cell receptors. the data from analysis of ,, T-cell repertoire showed that ,, T cells infiltrating the kidneys of IgAN patients use a restricted subset of ,, T cells with a feature of recurrent junctional amino acid motifs in V,1 T cells. the results suggest that both ,, and ,, T cells are involved in the progression of IgAN to renal failure and also that there is clonal expansion of individual ,, or ,, T cells in the kidneys of some IgAN patients. the conserved amino acid in the TCR CDR3 region of V,8 and the feature of recurrent junctional amino acid motifs in V,1 T cells may indicate antigen-driven selection. [source]

HLA-B8, DR3: a new risk factor for graft failure after renal transplantation in patients with underlying immunoglobulin A nephropathy

CLINICAL TRANSPLANTATION, Issue 5 2009
Margret B. Andresdottir
Abstract:, Background:, The HLA-B8, DR3 haplotype has been associated with high immune reactivity. In this study, we have tested whether this haplotype has differential effect on graft survival in patients with IgAN compared with control patients. Methods:, From the Eurotransplant Registry we analyzed graft survival of 1207 recipients with IgAN and 7935 control patients with non-glomerular diseases. Death-censored graft loss according to the HLA-B8, DR3 haplotype was calculated with Kaplan,Meier analysis and Cox-regression model was used to correct for various risk factors. Results:, The frequency of the HLA-B8, DR3 haplotype was significantly lower in IgAN patients compared with controls (10.3% vs. 15.4%, p < 0.001). Ten-year graft survival was identical in the control group with and without the HLA-B8, DR3 haplotype (71.1% and 70.2%, respectively), but significantly worse in IgAN patients carrying the HLA-B8, DR3 haplotype compared with patients without it (52.5% vs. 69.1%, respectively, p = 0.009). The risk of graft loss was increased by 66% (HR 1.6, 95% CI 1.14, 2.29) in IgAN with the HLA-B8, DR3 haplotype and independent of well-known risk factors. Conclusions:, We have identified a new risk factor for graft loss unique to patients with IgAN. This finding emphasizes the exclusive immune characteristics of IgAN patients after transplantation. [source]