Posttransplant anti-glomerular basement membrane nephritis occurs rarely in Alport patients and may be restricted to a subgroup with particular COL4A5 mutations.
The novel mutation reported here, COL4A5arg1677gln, has been detected in three independently ascertained Ashkenazi-American families, causes a relatively mild form of nephritis with typical onset in the fourth or fifth decade, and may be involved in the etiology of a large proportion of adult-onset hereditary nephritis in Ashkenazi Jews.
Three structural aberrations were found in COL4A5, in intragenic deletion, a Pst I site variant, and an uncharacterized abnormality, which appear to cause nephritis and deafness, with allele-specific severity, in three Alport syndrome kindreds in Utah.
Coordinate gene expression of the alpha3, alpha4, and alpha5 chains of collagen type IV. Evidence from a canine model of X-linked nephritis with a COL4A5 gene mutation.
Combined with previously reported data, these findings suggest that the incidence of deletions of COL4A5, as opposed to other COL4A5 mutations, is much higher in Alport patients who develop posttransplant anti-GBM nephritis than in the general Alport population.
We focus on the effect of mutations in the human MYH9 gene that encodes NMIIA, which have been implicated in the pathogenesis of various diseases including nephritis.
Thus, our results suggest that mutations in MYH9 result in three megakaryocyte/platelet/leukocyte syndromes and are important in the pathogenesis of sensorineural deafness, cataracts and nephritis.
In addition, FCGR2A-R131 allele was associated with a 1.186-fold (95 % CI 1.043-1.349) greater risk for the occurrence of nephritis in the Asians population with SLE.
Here we evaluated the relevance of Fc gamma RIIa gene polymorphism in the development of lupus immune complex (IC)-mediated nephritis by comparing the genotype and allelic distribution of this receptor in lupus nephritis to ethnically matched healthy controls in Brazilians.
Autosomal recessive Alport syndrome: mutation in the COL4A3 gene in a woman with Alport syndrome and posttransplant antiglomerular basement membrane nephritis.
In the nephritis group (n = 46), as well as the entire SLE cohort, there was a predominance of genotypes with low-binding alleles (FcgammaRIIa-R131 and FcgammaRIIIa-F176) at both loci (SLE nephritis patients 89% versus controls 62%; P < 0.002; odds ratio 0.20 [95% confidence interval 0.05-0.6] for risk of nephritis in individuals homozygous for either FcgammaRIIa-H131 or FcgammaRIIIaV176).
There was no skewing in FcgammaRIIa or FcgammaRIIIa genotypes between female SLE and female controls, but FcgammaRIIa-R131 allele showed skewing between female SLE with nephritis and female SLE without nephritis.
The role of Fc receptors in the induction and progression of Crgn is increasingly recognized, and our previous studies have shown that copy number variation in Fcgr3 partially explains the genetic susceptibility of the Wistar-Kyoto (WKY) rat to nephrotoxic nephritis, a rat model of Crgn.
The FcgammaRIIIa F/F genotype was also associated with nephritis (WHO class III and IV, P = 0.04 for the SLE group) and in combination with the CRP4 A-allele a stronger association was noted (P < 0.001).
Specifically, a polymorphism of FC gamma RIII, termed Fc gamma RIIIA-158F, has been found to be associated with SLE in 2 largely Caucasian populations and appeared to constitute a risk factor for nephritis.
Univariate and multivariate analyses demonstrated a striking association between the low-affinity FcgammaRIIIA-158F allele and FF genotype and the risk of nephritis among Caucasians, but not among non-Caucasians (multivariate odds ratio [OR] 2.6 for Caucasians with FF genotype), (P = 0.0017).
With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients.
We evaluated circulating antibodies to α-enolase by a dot blotting system and PLA<sub>2</sub>R by indirect immunofluorescence, and glomerular deposition of these proteins in 25 patients with primary MN, 20 patients with secondary MN, 44 patients with collagen disease or severe infection, 60 patients with nephritis (each ten patients of IgA nephropathy, focal segmental gloemrulosclerosis, minimal change nephrotic syndrome, membranoproliferative glomeurlonephritis, diabetic glomerulosclerosis, and tubulointerstitial nephritis) as disease control, and 20 healthy subjects.