Anti-Collagen Type IV polyclonal antibody [Biotin]

Collagen IV nephropathies (COL4Ns) comprise benign familial microscopic hematuria, thin basement membrane nephropathy (TBMN), X-linked Alport syndrome (AS) and also autosomal recessive and dominant AS. Apart from the X-linked form of AS, which is caused by hemizygous mutations in the COL4A5 gene, the other entities are caused by mutations in the COL4A3 or COL4A4 genes. The diagnosis of these conditions used to be based on clinical and/or histological findings of renal biopsies, but it is the new molecular genetics approach that revolutionised their investigation and proved particularly instrumental, especially, in many not so clear-cut cases. More recently, the spectrum of COL4N has expanded to include late onset focal segmental glomerulosclerosis (FSGS) that develops on top of TBMN in later life. Also, other reports showed that some patients with a primary diagnosis of familial FSGS proved to have variants in COL4 genes. In the presence of a renal biopsy picture of FSGS and in the absence of either electron microscopy studies or molecular genetic studies that point to TBMN and COL4N, the patient and his family may be mistakenly diagnosed with hereditary FSGS leading to unnecessary further investigations, erroneous family counselling and improper corticosteroid treatment. TBMN is a frequent finding in the general population, and according to several recent reports, it may be the underlying cause and the explanation for many familial and sporadic cases of late-onset FSGS with non-nephrotic proteinuria. This is an important new finding that needs widespread recognition. It is anticipated that the molecular genetic analysis with next generation sequencing will certainly offer timely correct diagnosis. (C) 2015 S. Karger AG, Basel

The glomerular basement membrane (GBM) is a critical component of the kidney's blood filtration barrier. Alport syndrome, a hereditary disease leading to kidney failure, is caused by the loss or dysfunction of the GBM's major collagen type IV (COLA) isoform alpha(3),alpha(4),alpha(5). The constituent COL4 alpha-chains assemble into heterotrimers in the endoplasmic reticulum before secretion into the extracellular space. If any one of the alpha(3)-,alpha(4)- or alpha(5)-chains is lost due to mutation of one of the genes, then the entire heterotrimer is lost. Patients with Alport syndrome typically have mutations in the X-linked COL4A5 gene or uncommonly have the autosomal recessive form of the disease due to COL4A3 or COL4A4 mutations. Treatment for Alport syndrome is currently limited to angiotensin-converting enzyme inhibition or angiotensin receptor blockers. Experimental approaches in Alport mice have demonstrated that induced expression of COL4A3. either widely or specifically in podocytes of Col4a3(-/-) mice, can abrogate disease progression even after establishment of the abnormal GBM. While targeting podocytes in vivo for gene therapy is a significant challenge, the more accessible glomerular endothelium could be amenable for mutant gene repair. In the present study, we expressed COL4A3 in Col4a3(-/-) Alport mice using an endothelial cell-specific inducible transgenic system, but collagen-alpha(3)alpha(4)alpha(5) (IV) was not detected in the GBM or elsewhere, and the Alport phenotype was not rescued. Our results suggest that endothelial cells do not express the Col4a3/a4/a5 genes and should not be viewed as a target for gene therapy.