Use of a Monoclonal Antibody in Differential Diagnosis of Children With Haematuria and Hereditary Nephritis

Savage, CarolineO.S.; Kershaw, Michael J.; Pusey, Charles D.; Barratt, T. M.; Reed, Alfred C.; Pincott, J R; Dillon, M J; Lockwood, C. M.

doi:10.1016/s0140-6736(86)91499-6

Cited by 21 publications

(5 citation statements)

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“…These investigators observed that glomeruli from patients with AS fail to bind human anti-GBM antibodies from patients with Goodpasture's syndrome, a ®nding suggesting that an antigen normally present in the GBM was absent in these patients and that the absent antigen was related to the nephritogenic antigen of Goodpasture's syndrome (GP). This observation was con®rmed by dierent studies using the same types of sera or monoclonal or polyclonal antibodies directed against the GP antigen (14,15,16,17). Overall, most male patients showed absence or reduced binding of the antibodies to the GBM, but this phenomenon was not universal, con®rming the heterogeneity of AS.…”

Section: Distribution Of a (Iv) Chain In Alport's Syndromementioning

confidence: 86%

Renal Pathology and Ultrastructural Findings in Alport's Syndrome

Nôël

2000

Renal Failure

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Morphological study of the kidney is generally the first step in the diagnosis of Alport's syndrome. Light microscopy study allows to suggest the diagnosis with the association of focal and segmental glomerulosclerosis, GBM anomalies when studied with silver staining, interstitial foam cells, and negative standard immunofluorescence study. GBM anomalies observed by electron microscopy are nearly specific with thickening splitting and fragmenting of the lamina densa. GBM anomalies are the consequence of a collagen IV disease. Thus, immunohistochemical results obtained with 6 different alpha(IV) are essential and allow to evaluate the mode of inheritance. Schematically, in the X dominant AS form, GBM, distal tubular BM and collecting duct BM do not express alpha3/alpha4, alpha5(IV). In the autosomic recessive AS form, collecting duct BM alone express alpha5(IV) without expression of alpha3(IV) and alpha5(IV) chains along the GBM and distal TBM.

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Section: Distribution Of a (Iv) Chain In Alport's Syndromementioning

confidence: 86%

Renal Pathology and Ultrastructural Findings in Alport's Syndrome

Nôël

2000

Renal Failure

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“…Further immunological studies provided more evidence for the hypothesis that the GBM of Alport patients may lack the Goodpasture antigen. In these studies, a monoclonal antibody to the Goodpasture antigen failed to react with the GBM of some Alport families [45]. Over the past few years, various groups have identified the C-terminal globular domain of type IV collagen as the target antigen of the Goodpasture autoantibodies [6,16,25,44,[49][50][51][52].…”

Section: Histological and Biochemical Findingsmentioning

confidence: 99%

Molecular aspects of Alport's syndrome

1992

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We review the recent progress achieved on the understanding of the molecular basis of Alport's syndrome. This inherited disease is defined as progressive nephritis with sensorineural hearing loss. In 80%-85% of the families, inheritance is compatible with X-linked dominant transmission, whereas in the remaining cases autosomal dominant transmission is assumed. Histology studies demonstrated that the main defect is within the glomerular basement membrane (GBM). In addition, evidence for an altered GBM antigenicity came from immunofluorescence studies which showed a reduced or absent binding of anti-GBM autoantibodies or monoclonal antibodies to the "Goodpasture antigen" in some families. Subsequent studies added substantial evidence that Alport's syndrome is a type IV collagen disease. Genetic linkage analyses coherently identified an Alport locus at the X-chromosomal region Xq21.3-22. Recently, a previously unknown alpha 5 chain of type IV collagen was identified, and the corresponding gene was also mapped to Xq22. Subsequent studies on Alport families by various groups identified more than 25 COL4A5 lesions. Segregation in linkage with the Alport phenotype could be shown in large kindreds. Mainly deletions and only a few point mutations were described. Most lesions reported so far are heterogeneous. We were able to identify two deletions and one point mutation involving a 3' splice site in 20 Alport families from Germany. One of the patients with a COL4A5 deletion and the patient with the splice site mutation developed anti-GBM antibodies after renal transplantation. In contrast, no COL4A5 lesions have been found in 2 further patients with posttransplant anti-GBM nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…This same antigen seems to be the target for antibasement mem brane antibody, i.e. the Goodpasture antigen is absent in Alport's hereditary nephritis [22,23]. Either free C 1C [24] or circulating anti-GBM antibody [25] can initiate platelet aggregation which leads on to intraglomerular capillary coagulation [26,27] because of the special function of the glomerular filters.…”

Section: Immune Complexes or Antibodies To Fixed Glomerular Antigensmentioning

confidence: 99%

Cells and Mediators in Glomerulonephritis

Wardle

1988

Nephron

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Use of a Monoclonal Antibody in Differential Diagnosis of Children With Haematuria and Hereditary Nephritis

Cited by 21 publications

References 5 publications

Renal Pathology and Ultrastructural Findings in Alport's Syndrome

Renal Pathology and Ultrastructural Findings in Alport's Syndrome

Molecular aspects of Alport's syndrome

Cells and Mediators in Glomerulonephritis

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