A genome-wide association study further showed a highly significant association of the PLA2R1 and the HLA-DQA1 loci with idiopathic MN in patients of white ancestry.
Several other rare antigens have been described, including antibodies against neutral endopeptidase as a cause of antenatal MN and circulating cationic bovine serum albumin as an antigen with implications in childhood MN.
Among DM patients without DR, patients with membranous nephropathy had significantly lower levels of serum albumin and serum creatinine, and significantly higher levels of high-density lipoprotein and cholesterol than those with DN.In conclusion, DN patients without DR may have less serious renal damage and less diabetic complication than those with DR.
These studies led to the identification of neutral endopeptidase, the type-M phospholipase A2 receptor (PLA2R), and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in neonatal alloimmune, adult 'idiopathic', and early childhood MN, respectively.
Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein.
Heparanase activity, albumin, HS and creatinine were measured in the urine of patients with T1D (n=58) or T2D (n=31), in patients with MGP (n=52) and in healthy controls (n=10).
The experimental MGN rat models induced by cationic bovine serum albumin were established by a modified Border's method and applied in the pharmacodynamics study of ME BSA NPs.
Kidney function was assessed by proteinuria for 24 hours, serum albumin, blood urea nitrogen (BUN), serum creatine, serum cystatin C. We assessed the correlation between anti-PLA2R antibody levels and clinical parameter in the PMN patients.
It is remarkable that experimental models such as Heymann nephritis and cationic bovine serum albumin-induced MN in the rabbit predicted the pathomechanisms of the human glomerulopathy.
PLA2R-associated MN was initially found to associate with risk alleles within <i>HLA-DQA1</i>, but subsequent studies have shifted the focus to the HLA-DRB locus.
Different HLA-DR2 alleles were associated with different pathologic subtypes of HBV-GN: DRB1*1502 with membranoproliferative glomerulonephritis (MPGN, n = 35) (OR = 14.5) and DRB1*1501 with membranous nephropathy (MN, n = 11) (OR = 3.8).
Although DRB1*1502, which differs from DRB1*1501 by a single amino acid, was not a risk allele for primary membranous nephropathy (odds ratio 1.01), it was associated with significantly lower estimated glomerular filtration rates both at baseline (1.79, 1.18-2.72) and at last follow-up (1.72, 1.17-2.53), a significantly worse renal outcome by Kaplan-Meier analysis and a significantly higher risk of end-stage renal disease by Cox regression analysis (hazard ratio 4.52, 1.22-16.74).
The discussed study identifies a novel allele, HLA DRB1*1502, in a Han Chinese cohort that acts as a modifier allele by associating not with the phenotype of membranous nephropathy, but rather with the severity of disease.
However, megalincannot be held responsible for human MN because it has not been found in human podocytes or detected in subepithelial immune deposits in patients with MN.
The pathogenesis of Heymann nephritis, a rat model of human membranous glomerulonephritis, depends on the interaction of autoantibodies with a renal glycoprotein (GP330) on glomerular podocytes.