Search results for "Glomerular Basement Membrane"
showing 10 items of 13 documents
Genome-wide association study of diabetic kidney disease highlights biology involved in renal basement membrane collagen
2018
Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 individuals with type 1 diabetes (T1D) using a spectrum of DKD definitions basedon albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain(COL4A3)gene, which encodes a major structural component of the glomerular basement membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definit…
Anti-glomerular basement membrane antibody-mediated glomerulonephritis due to glue sniffing
1987
A 16-year-old girl developed rapidly progressive glomerulonephritis and renal failure. The disease was associated with high titres of antiglomerular basement membrane antibodies in serum, linear deposits of immunoglobulin G and diffuse epithelial crescents on renal biopsy. Past history revealed heavy smoking and deliberate sniffing of Pattex glue, a mixture of hydrocarbons which possibly may affect the structure of glomerular basement membrane. After treatment by repeated plasmapheresis and drug immunosuppression autoantibodies disappeared from serum but renal function was not influenced. Renal damage is a potential hazard for glue sniffing adolescents.
IgG Subclass Distribution of Autoantibodies to Glomerular Basement Membrane in Goodpasture’s Syndrome Compared to Other Autoantibodies
1988
The IgG subclass distribution of autoantibodies to glomerular basement membrane (anti-GBM antibodies) was investigated and compared to the distribution of liver-kidney microsomal (LKM) autoantibodies in chronic active hepatitis, to antimitochondrial autoantibodies (AMA) in primary biliary cirrhosis, and to the subclass distribution of total serum IgG within a healthy population. Solid phase assays for the demonstration of these autoantibodies were performed with four mouse monoclonal antibodies specific for each human subclass to provide quantitative data for the autoantibodies. In addition, the subclass distribution of total IgG in these sera was analyzed. IgG1 accounted for 75% of the tot…
Glomerular basement membrane: evidence for collagenous domain of the alpha 3 and alpha 4 chains of collagen IV.
1990
Abstract A collagenous component(s) of Mr = 60K was extracted from glomerular basement membrane with urea and was purified. Upon digestion, it yielded a collagenase-resistant fragment(s) of Mr = 23.5K. Both component and fragment showed immunochemical identity with the noncollagenous domains of the new α3 & α4 chains of collagen IV. The component is characterized by a collagenous domain of about 280 residues and a noncollagenous domain of about 250 residues. These findings further establish these new chains as distinct entities of collagen IV.
Antiglomerular basement membrane antibodies in human sera: Detection by a modified micro-ELISA
1985
An enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to human glomerular basement membrane has been developed. Special emphasis has been put on the choice of microtiter plates which were coated with a collagenase digest of human glomerular basement membrane. Results differed markedly between the different microtiter plates. Best results were obtained with a flexible polyvinylchloride microtiter plate with flat wells (Dynatec). This plate exhibited the highest positive/negative ratio and the lowest intraassay standard deviation. Optimal conditions for each step in the ELISA have been determined. The assay proved to be specific, sensitive, and reproducible. Circulating ant…
Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen
2019
BACKGROUND: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown.METHODS: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.RESULTS: Our GWAS meta-analysis included association result…
Characterization and Expression of Multiple Alternatively Spliced Transcripts of the Goodpasture Antigen Gene Region. Goodpasture Antibodies Recogniz…
1995
Collagen IV, the major component of basement membranes, is composed of six distinct alpha chains (alpha 1-alpha 6). Atypically among the collagen IV genes, the exons encoding the carboxyl-terminal region of the human alpha 3(IV) chain undergo alternative splicing. This region has been designated as the Goodpasture antigen because of its reactivity in the kidney and lung with the pathogenic autoantibodies causing Goodpasture syndrome. The data presented in this report demonstrate that, in human kidney, the gene region encompassing the Goodpasture antigen generates at least six alternatively spliced transcripts predicting five distinct proteins that differ in their carboxyl-terminus and retai…
Increased Goodpasture antigen-binding protein expression induces type IV collagen disorganization and deposit of immunoglobulin A in glomerular basem…
2007
Increased expression of Goodpasture antigen-binding protein (GPBP), a protein that binds and phosphorylates basement membrane collagen, has been associated with immune complex-mediated pathogenesis. However, recent reports have questioned this biological function and proposed that GPBP serves as a cytosolic ceramide transporter (CERTL). Thus, the role of GPBP in vivo remains unknown. New Zealand White (NZW) mice are considered healthy animals although they convey a genetic predisposition for immune complex-mediated glomerulonephritis. Here we show that NZW mice developed age-dependent lupus-prone autoimmune response and immune complex-mediated glomerulonephritis characterized by elevated GP…
Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of…
2020
IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present …
Alport's syndrome: specificity and pathogenesis of glomerular basement membrane alterations.
1987
In Alport's syndrome (AS) thinning and splitting of the glomerular basement membrane (GBM) are assumed to be characteristic ultrastructural alterations. Both lesions are, however, non-specific because they can occur in other glomerulopathies. In addition, splitting may be found in non-glomerular structures. It should be emphasized that the characteristic lesion in AS is a result of the widespread combination of thin and split GBM in the same biopsy specimen. In our opinion the basic lesion is the thin GBM, which is characterized by a lamina densa (measuring 50-150 nm in thickness) which may begin to split as a result of focal detachment of podocyte pedicles (spacing) and repeated subepithel…