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      Renal Phospholipase A2 Receptor and the Clinical Features of Idiopathic Membranous Nephropathy

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          Abstract

          Background:

          According to the renal phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (iMN) could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN.

          Methods:

          A total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence. Among these patients, 186 (80.5%) with complete baseline clinical data were used for further study. Urinary protein excretion, serum albumin, and creatinine were analyzed. For those patients with follow-up longer than 1 year, the relationship between PLA2R and response to immunosuppressants were analyzed. The t-test was used for parametric analysis and the Mann-Whitney U-test was used for nonparametric analysis. Categorical variables were described as frequencies or percentages, and the data were analyzed with Pearson's Chi-square test or Fisher's exact test.

          Results:

          Of the 231 iMN patients, 189 showed renal detectable PLA2R expression (81.8%). The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated ( n = 145) and non-PLA2R-associated iMN patients ( n = 41). However, about 1/3 of the non-PLA2R-associated iMN had abnormal serological tests, significantly more common than PLA2R-associated iMN (31.7% vs. 8.3%, P = 0.000). The non-PLA2R-associated iMN had lower C4 levels compared with PLA2R-associated iMN ( P = 0.004). The non-PLA2R-associated iMN patients also showed a better response to immunosuppressants (complete remission [CR] 42.9%; partial remission [PR] 14.3%) compared with PLA2R-associated iMN (CR 3.2%; PR 48.4%, P = 0.004) at the 3 rd month.

          Conclusions:

          There were no significant differences in serum creatinine, albumin, and urine protein excretion between PLA2R-associated and non-PLA2R-associated iMN, while the non-PLA2R-associated iMN patients showed more abnormal serological tests. The non-PLA2R-associated iMN seemed to respond more quickly to the immunosuppressive therapy compared with PLA2R-associated iMN.

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          Most cited references 11

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          Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy.

          The phospholipase A(2) receptor (PLA(2)R) is the major target antigen in idiopathic membranous nephropathy. The technique for measuring antibodies against PLA(2)R and the relationship between antibody titer and clinical characteristics are not well established. Here, we measured anti-PLA(2)R (aPLA(2)R) antibody titer and subclass in a well defined cohort of 117 Caucasian patients with idiopathic membranous nephropathy and nephrotic-range proteinuria using both indirect immunofluorescence testing (IIFT) and ELISA. We assessed agreement between tests and correlated antibody titer with clinical baseline parameters and outcome. In this cohort, aPLA(2)R antibodies were positive in 74% and 72% of patients using IIFT and ELISA, respectively. Concordance between both tests was excellent (94% agreement, κ=0.85). Among 82 aPLA(2)R-positive patients, antibody titer significantly correlated with baseline proteinuria (P=0.02). Spontaneous remissions occurred significantly less frequently among patients with high antibody titers (38% versus 4% in the lowest and highest tertiles, respectively; P<0.01). IgG4 was the dominant subclass in the majority of patients. Titers of IgG4, but not IgG1 or IgG3, significantly correlated with the occurrence of spontaneous remission (P=0.03). In summary, these data show high agreement between IIFT and ELISA assessments of aPLA(2)R antibody titer and highlight the pathogenetic role of these antibodies, especially the IgG4 subclass, given the observed relationships between aPLA(2)R titer, baseline proteinuria, and outcome.
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            PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy.

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              Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy.

              The M-type phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients. In retrospective studies, the PLA2R-autoantibody titer in the serum was sometimes negative indicating their measurement alone may be inconclusive. In order to better differentiate between primary and secondary membranous nephropathy, we conducted a prospective study that included 88 patients with a histologic diagnosis of membranous nephropathy. Immunohistochemical analysis for PLA2R was faintly positive in kidneys from normal individuals and patients with various other glomerular injuries. In 61 of the 88 patients, PLA2R expression was strongly positive in glomeruli, and in 60 of these patients PLA2R autoantibodies were also detected in the serum. The 27 patients negative for serum PLA2R autoantibodies were faintly positive for PLA2R staining in glomeruli and in 15 of these patients a secondary cause was found. The remaining 12 patients have a yet undetected secondary cause of membranous nephropathy or have different glomerular antigens other than PLA2R. Thus, increased staining for PLA2R in glomeruli of renal biopsies tightly correlates with the presence of PLA2R autoantibodies in the serum and this may help discriminate between primary and secondary membranous nephropathy.
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                Author and article information

                Journal
                Chin Med J (Engl)
                Chin. Med. J
                CMJ
                Chinese Medical Journal
                Medknow Publications & Media Pvt Ltd (India )
                0366-6999
                20 April 2017
                : 130
                : 8
                : 892-898
                Affiliations
                [1 ]Department of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China
                [2 ]Department of Nephrology, Wuxi People's Hospital, Wuxi, Jiangsu 214023, China
                Author notes
                Address for correspondence: Dr. Zhu-Xing Sun, Department of Nephrology, Wuxi People's Hospital, 299 Qingyang Road, Wuxi, Jiangsu 214023, China E-Mail: sunzhx@ 123456wuxiph.com
                Article
                CMJ-130-892
                10.4103/0366-6999.204096
                5407034
                28397717
                Copyright: © 2017 Chinese Medical Journal

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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