Nephrology 2011: Steadily Moving Forward (I) Author: Nanjing General Hospital, Nanjing Military Region, Nanjing, China All Army Institute of Nephrology Liu Zhihong, Hu Weixin, Li Shijun, Xie Honglang, Huang Xianghua, Gong Huahua, Yu Yusheng, Zhang Haitao Source: China Medical Tribune Date: 2012-01-16 This article is available from www.cmt.com.cn ■ Primary Glomerular Diseases Anti-PLA2R Antibodies and Idiopathic Membranous Nephropathy Anti-M-type phospholipase 2 receptor (PLA2R) antibodies were first identified as the causative antibodies in idiopathic membranous nephropathy in 2009, and during the past 1 year, there have been new developments in related research. Wang Yanjun, Department of Nephrology, Affiliated Hospital of Qinghai University PLA2R is also a major target antigen in idiopathic membranous nephropathy in China In 2011, Qin et al. published a study in the Journal of the American Society of Nephrology (J Am Soc Nephrol) showing that anti-PLA2R antibodies were detected in 49 of 60 patients (82%) with membranous nephropathy; using a more sensitive assay, anti-PLA2R antibodies were detected in 10 of the remaining 11 patients. Anti-PLA2R antibodies were detectable in low titers in 10 of the remaining 11 patients, whereas in other secondary membranous nephropathies [e.g., lupus nephritis type V, hepatitis B virus (HBV)-associated membranous nephropathy, tumor-associated membranous nephropathy], the detection rate of anti-PLA2R antibodies was very low. Anti-PLA2R antibody titers predict the efficacy of rituximab in membranous nephropathy In another study published in the Journal of the American Society of Nephrology, investigators looked at changes in anti-PLA2R autoantibody titers and proteinuria in 35 patients with membranous nephropathy before and after treatment with rituximab. The results were that 25 patients (71%) were positive for anti-PLA2R autoantibodies before treatment; after 12 months of rituximab treatment, antibody titers decreased or turned negative in 17 patients (68%). Among those whose antibody titers decreased or turned negative, 59% (12 months) and 88% (24 months) of patients achieved complete or partial remission of proteinuria, respectively, while only 0% (12 months) and 33% (24 months) of those with persistent positive antibodies achieved complete or partial remission. This study observed that the decrease in anti-PLA2R antibody titers preceded the decrease in proteinuria (Figure 1); one patient also had a relapse followed by a reversion of his anti-PLA2R antibodies to positive. Other possible pathogenesis of idiopathic membranous nephropathy Some children with membranous nephropathy receive dietary intervention or override immunosuppressive therapy A study published in the New England Journal of Medicine (N Engl J Med) in June 2011 showed that cationic bovine serum albumin antigen and its antibodies (IgG1 and IgG4 subtypes, Figure 2) were detectable in the sera of some children with membranous nephropathy. At the same time, bovine serum albumin was detected in immune deposits on the epithelial side of the glomerulus. This suggests that bovine serum albumin with cations in the serum can form in situ immune complexes with anionic basement membranes; special dietary interventions may be more important than immunosuppressive therapy in some children with membranous nephropathy. The HLA-DQA1 gene is closely associated with idiopathic membranous nephropathy British scholars found through genome-wide association studies that the gene PLA2R1 [single nucleotide polymorphism (SNP) rs4664308, P=8.6×10-29] encoding the M-type phospholipase A2 receptor located on chromosome 2q24 and the allele of HLA-DQA1 on chromosome 6p21 (SNP rs2187668, P=8.0×10-93) were strongly associated with idiopathic membranous nephropathy, and the ratio (OR) of idiopathic membranous nephropathy was as high as 78.5 in those carrying the pure congeners of these two alleles; among them, those with the chromosome 6p21 allele HLA-DQA1 were more likely to produce autoantibodies against PLA2R1. This suggests that HLA genes also play an important regulatory role in the pathogenesis of idiopathic membranous nephropathy. The study was published in the New England Journal of Medicine in February 2011.