Antigens of the human glomerular basement membrane

Fouser, Laurie S.; Michael, Alfred F.

doi:10.1007/bf00197212

Cited by 16 publications

(13 citation statements)

References 121 publications

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“…The literature was first surveyed to identify Ags that were known to be expressed in the glomerular milieu and/or GBM (43)(44)(45). Total glomerular sonicates were obtained by harvesting glomeruli from B6 mouse kidneys and sonicating them as described previously (46,50).…”

Section: Methodsmentioning

confidence: 99%

“…The purpose of the present study was to adopt a similar multiplexed approach to define the spectrum of autoantibodies reactive with different glomerular or glomerular basement membrane (GBM) Ags, which best correlate with disease activity and may be present in lupus. To this end, a panel of Ags documented to be present in the glomeruli/GBM (43)(44)(45) was spotted onto specially precoated glass slides; these arrays have been termed glomerular proteome arrays. These novel proteome microarrays were then used to analyze the nephrophilic autoantibody profiles in murine and human lupus.…”

Section: Introductionmentioning

confidence: 99%

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Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays

Zhen

Xie

Wu³

et al. 2005

J. Clin. Invest.

218

101

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Nephrophilic autoantibodies dominate the seroprofile in lupus, but their fine specificities remain ill defined. We constructed a multiplexed proteome microarray bearing about 30 antigens known to be expressed in the glomerular milieu and used it to study serum autoantibodies in lupus. Compared with normal serum, serum from B6.Sle1.lpr lupus mice (C57BL/6 mice homozygous for the NZM2410/NZW allele of Sle1 as well as the FAS lpr defect) exhibited high levels of IgG and IgM antiglomerular as well as anti-double-stranded DNA/chromatin Abs and variable levels of Abs to α-actinin, aggrecan, collagen, entactin, fibrinogen, hemocyanin, heparan sulphate, laminin, myosin, proteoglycans, and histones. The use of these glomerular proteome arrays also revealed 5 distinct clusters of IgG autoreactivity in the sera of lupus patients. Whereas 2 of these IgG reactivity clusters (DNA/chromatin/glomeruli and laminin/myosin/Matrigel/vimentin/heparan sulphate) showed association with disease activity, the other 3 reactivity clusters (histones, vitronectin/collagen/chondroitin sulphate, and entactin/fibrinogen/hyaluronic acid) did not. Human lupus sera also displayed 2 distinct IgM autoantibody clusters, one reactive to DNA and the other apparently polyreactive. Interestingly, the presence of IgM polyreactivity in patient sera was associated with reduced disease severity. Hence, the glomerular proteome array promises to be a powerful analytical tool for uncovering novel autoantibody disease associations and for distinguishing patients at high risk for end-organ disease.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays

Zhen

Xie

Wu³

et al. 2005

J. Clin. Invest.

218

101

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“…The extracellular matrices (ECM) of the glomerular mesangium and components of glomerular basement mem brane have been found to consist of type IV collagen, laminin, fibronectin and heparan sulfate proteoglycan (HSPG) by biochemical and immunochemical analyses [8]. The authors reported that staining of type IV collagen, laminin and fibronectin was detected in the glomerular capillary walls and /or mesangial areas in the advanced stage of patients with IgA nephropathy by immunohistochemistry [9,10].…”

Section: Introductionmentioning

confidence: 99%

IgA Deposits Might Not Influence the Production of Extracellular Matrix in Glomeruli of ddY Mice, a Spontaneous Animal Model for IgA Nephropathy

Tsushima

Tomino²,

Shimizu³

et al. 1994

Nephron

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Immunofluorescence studies were carried out to determine whether the expression of extracellular matrix (ECM) in glomeruli of ddY mice, a model for IgA nephropathy (Berger’s disease), is influenced by treatment with a rat monoclonal antibody to murine CD4 molecules (mAb CD4). This mAb CD4 showed a selective decrease in the number of CD4⁺ T cells in the peripheral blood of ddY mice as described previously. The ddY mice were initially treated with intravenous injections, followed by weekly intraperitoneal injections of mAb CD4. In immunofluorescence, the mean intensity of IgA deposits in the renal glomerular mesangial areas and capillary walls of the treated ddY mice was significantly lower than that in saline-treated control mice at comparable ages. There was no significant difference in the distribution or intensity of ECM components, i.e. type IV collagen, fibronectin and heparan sulfate proteoglycan, in glomeruli between the mAB CD4-treated and the control ddY mice. In light microscopy, mesangial expansion in the treated ddY mice was milder than that found in the saline control mice. No significant differences in the average number of intraglomerular cells, levels of serum IgA and urinary protein between the treated and control ddY mice were observed. Thus, it appears that although CD4⁺ T cells modulate the amounts of glomerular IgA deposits, other factors may be involved in the expression of ECM in glomeruli of IgA nephropathy in ddY mice.

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“…The GBM consists of type IV collagen, laminin, heparan sulfate proteoglycan, fibronectin and other proteins [13]. Type IV collagen is a major component of the GBM and mesangial matrix, and its molecule is composed of two α1(IV) chains and one α2(IV) chain [14, 15, 16].…”

Section: Introductionmentioning

confidence: 99%

Glomerular Expression of α2(IV) and α5(IV) Chains of Type IV Collagen in Patients with IgA Nephropathy

Kamimura¹,

Honda²,

Nitta³

et al. 2002

Nephron

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IgA nephropathy (IgAN) frequently accompanies glomerular basement membrane (GBM) alterations. To clarify the compositional changes of the GBM in IgAN, we examined the glomerular expression of α2(IV) and α5(IV) chains of type IV collagen in 36 patients with IgAN. Increased expression of the α2(IV) chain was observed in the expanded mesangium, and there were segmental sclerotic lesions of glomeruli in which the expression of the α5(IV) chain in the GBM was reduced. These lesions were found in 11 out of the 36 patients (30.6%). The patients with these lesions had more proteinuria, lower creatinine clearance and severer histological changes than the patients without them. On the other hand, a partial reduction of α5(IV) chain in normal-appearing GBM was observed in 15 out of the 36 patients (41.7%). The patients with this lesion had a longer disease period before biopsy than the patients without it. No other clinical and histological parameters were related to the partial reduction of α5(IV) in the GBM. In conclusion, an imbalance of glomerular α2(IV) and α5(IV) chain expression occurred in IgAN. This may be associated with the morphological changes of glomerular sclerosis and GBM alterations in IgAN. Further studies are required to understand the pathogenesis of the abnormal expression of type IV collagen chains.

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Antigens of the human glomerular basement membrane

Cited by 16 publications

References 121 publications

Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays

Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays

IgA Deposits Might Not Influence the Production of Extracellular Matrix in Glomeruli of ddY Mice, a Spontaneous Animal Model for IgA Nephropathy

Glomerular Expression of α2(IV) and α5(IV) Chains of Type IV Collagen in Patients with IgA Nephropathy

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