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      Expression of phospholipase A2 receptor and IgG4 in patients with membranous nephropathy

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          Abstract

          Objectives

          The aims of this study were to detect the expression of M phospholipase A2 receptor (PLA2R) in the kidney tissue of patients with idiopathic membranous nephropathy (IMN), secondary membranous nephropathy (SMN), and the nonmembranous nephropathy (non-MN), to evaluate the value of PLA2R in the kidney tissue and serum anti-PLA2R antibody in the diagnosis of membranous nephropathy (MN), and to explore the relationship between PLA2R of the kidney tissue or serum anti-PLA2R antibody and clinical features of MN.

          Methods

          The kidney tissue was collected by kidney biopsy. Immunofluorescence assay was used to detect the level of PLA2R and IgG4 antigen in kidney tissue. Furthermore, the level of the PLA2R was detected using the enzyme-linked immunosorbent assay (ELISA). The positive and negative rates of PLA2R and IgG4 in different diseases and the sensitivity and specificity, were calculated using the statistical method. The specificity and coincidence rate of PLA2R or anti-PLA2R used in the differential diagnosis of IMN and SMN were evaluated.

          Results

          The expression intensities of anti-PLA2R antibody and IgG4 were significantly higher in patients with IMN than in patients with SMN but are not non-MN. There was no significant difference in anti-PLA2R antibody and IgG4 in patients with SMN and non-MN. The coincidence rate of serum anti-PLA2R antibody and PLA2R in kidney tissue was 100%.

          Conclusion

          The expression of PLA2R and IgG4 antibody had great significance in the pathological diagnosis of MN. The detection of the serum anti-PLA2R antibody had great diagnostic value in diagnosing MN.

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          Most cited references22

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          Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in China.

          The effect of air pollution on the changing pattern of glomerulopathy has not been studied. We estimated the profile of and temporal change in glomerular diseases in an 11-year renal biopsy series including 71,151 native biopsies at 938 hospitals spanning 282 cities in China from 2004 to 2014, and examined the association of long-term exposure to fine particulate matter of 70 μg/m(3) We also found that higher 3-year average air quality index was associated with increased risk of MN. In conclusion, in this large renal biopsy series, the frequency of MN increased over the study period, and long-term exposure to high levels of PM2.5 was associated with an increased risk of MN.
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            Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy.

            Rituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituximab (375 mg/m(2)) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0-145.4) months, 84 of 132 rituximab-treated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA2R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA2R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; P<0.001) strongly predicted remission. All 25 complete remissions were preceded by complete anti-PLA2R antibody depletion. On average, 50% anti-PLA2R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% CI, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% CI, 2.37 to 18.53; P<0.001). Eighteen patients achieved persistent antibody depletion and complete remission and never relapsed. Outcome was independent of PLA2R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating anti-PLA2R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN.
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              Membranous glomerulonephritis is a manifestation of IgG4-related disease.

              IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that typically manifests as fibro-inflammatory masses that can affect nearly any organ system. Renal involvement by IgG4-RD usually takes the form of IgG4-related tubulointerstitial nephritis, but cases of membranous glomerulonephritis (MGN) have also been described. Here we present a series of 9 patients (mean age at diagnosis 58 years) with MGN associated with IgG4-RD. All patients showed MGN on biopsy, presented with proteinuria (mean 8.3 g/day), and most had elevated serum creatinine (mean 2.2 mg/dl). Seven patients had known extrarenal involvement by IgG4-RD, with 5 patients having concurrent IgG4-related tubulointerstitial nephritis. Immunohistochemical analysis for the phospholipase A2 receptor, a marker of primary MGN, was negative in all 8 biopsies so examined. Six of 7 patients with available follow-up (mean 39 months) were treated with immunosuppressive agents; one untreated patient developed end-stage renal disease and underwent transplantation, without recurrence at 12 years after transplant. All 6 treated patients showed decreased proteinuria (mean 1.2 g/day), and most showed decreased serum creatinine (mean 1.4 mg/dl). Thus, MGN should be included in the spectrum of IgG4-RD and should be suspected in proteinuric IgG4-RD patients. Conversely, patients with MGN and an appropriate clinical history should be evaluated for IgG4-RD.
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                Author and article information

                Journal
                Vasc Health Risk Manag
                Vasc Health Risk Manag
                Vascular Health and Risk Management
                Vascular Health and Risk Management
                Dove Medical Press
                1176-6344
                1178-2048
                2018
                29 May 2018
                : 14
                : 103-108
                Affiliations
                [1 ]Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Anhui, People’s Republic of China
                [2 ]Department of Physiology, Bengbu Medical College, Anhui, People’s Republic of China
                Author notes
                Correspondence: Lijuan Yang, Department of Physiology, Bengbu Medical College, 2600 Donghai Road, Bengbu, Anhui 233030, People’s Republic of China, Tel +86 180 9655 9911, Email bbmcylj@ 123456163.com
                Article
                vhrm-14-103
                10.2147/VHRM.S160883
                5983022
                4b31bb2d-436e-4eec-9871-3b70f1084e84
                © 2018 Liu et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Cardiovascular Medicine
                membranous nephropathy,pla2r,igg4
                Cardiovascular Medicine
                membranous nephropathy, pla2r, igg4

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