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      Prevalence of serum anti M-type phospholipase A 2 receptor antibody in primary membranous nephropathy: A single center experience

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          Abstract

          We conducted a prospective study to assess utility of detection of antibodies to phospholipase A 2receptor (PLA 2R) in the serum of patients with membranous nephropathy. Seventy five patients with biopsy proven membranous nephropathy admitted between January 2011 and September 2014 were studied. Serum anti- PLA 2R was tested by indirect immunofluorescence. The test was positive in 45 out of 60 patients with primary membranous nephropathy (PMN) and in none of the 15 patients with secondary membranous nephropathy, with a sensitivity of 75% and specificity of 100% for PMN. Anti PLA 2R positivity also showed a significant correlation with quantum of proteinuria and negative correlation with serum albumin. This study has validated detection of serum anti PLA 2R in PMN as a non invasive diagnostic tool in Indian patients.

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          Most cited references 9

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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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            An immunofluorescence test for phospholipase-A₂-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis.

            The recent finding that phospholipase-A(2)-receptor antibodies (PLA(2)R-AB) may play a role in the development of primary membranous glomerulonephritis (MGN) offers the opportunity to measure a marker to help diagnose, classify and eventually monitor the course of patients with MGN. We developed an immunofluorescence test, which allows the easy and specific analysis of the presence of PLA(2)R-AB in serum. The usefulness of this test was studied in 153 healthy blood donors, 90 patients with non-membranous glomerular injuries, 17 patients with a secondary form of MGN and 100 patients with biopsy-proven primary MGN. In addition, in five patients with biopsy-proven MGN, PLA(2)R-AB levels were monitored prospectively for up to 18 months following a single dose of rituximab (RTX) (375 mg/m(2) body surface). PLA(2)R-AB were not found in healthy controls or patients with glomerular lesions other than biopsy-proven primary MGN. Fifty-two patients with primary MGN (52%) were positive for PLA(2)R-AB. The levels ranged from 1:10 to 1:3200. In patients who had MGN and were treated with RTX the fall in PLA(2)R-AB levels was followed by a decrease in proteinuria, whereas an increase in PLA(2)R-AB levels was associated with an increase in proteinuria. These studies show that the new test allows the monitoring of PLA(2)R-AB levels in patients with MGN and may help in making therapeutic decisions for these patients.
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              Autoantibodies against Phospholipase A2 Receptor in Korean Patients with Membranous Nephropathy

              The data were presented in abstract form at the 45th meeting of the American Society of Nephrology, October 30-November 04 2012, San Diego, CA, USA. Circulating autoantibodies against M-type phospholipase A2 receptor (PLA2R) are important pathogenic antibodies of idiopathic membranous nephropathy (MN) in adults. However, previous studies on the clinical impact of anti-PLA2R antibodies demonstrated several limitations, including insufficient numbers of study subjects and different time points and methods for anti-PLA2R antibody measurement. To verify the clinical significance of anti-PLA2R antibodies in Korean patients with MN, we measured autoantibodies in serum samples obtained at the time of biopsy from a total of 100 patients with idiopathic MN who had not yet received immunosuppressive treatment. We detected anti-PLA2R antibody in 69 patients, and we observed that autoantibody reactivity reflected the severity of disease activity. Proteinuria and hypoalbuminemia were more severe in patients with anti-PLA2R than in those without the autoantibodies (2.95 g/g vs. 6.85 g/g, P = 0.003; 3.1 g/dL vs. 2.5 g/dL, P = 0.004, respectively). Additionally, the clinical severities worsened proportionally as the levels of anti-PLA2R antibodies increased (P = 0.015 and P for trend <0.001 for proteinuria and hypoalbuminemia, respectively). However, neither the levels nor the presence or absence of anti-PLA2R antibody showed a significant correlation with clinical outcomes, such as remission rate and time to remission. In conclusion, we observed that anti-PLA2R antibodies are highly prevalent in Korean patients with idiopathic MN and that they reflect the clinical disease activity before the administration of immunosuppressive treatment. However, the levels of anti-PLA2R antibody at the time of kidney biopsy may not predict the clinical outcomes in current clinical practice.
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                Author and article information

                Journal
                Indian J Nephrol
                Indian J Nephrol
                IJN
                Indian Journal of Nephrology
                Medknow Publications & Media Pvt Ltd (India )
                0971-4065
                1998-3662
                Jul-Aug 2016
                : 26
                : 4
                : 257-261
                Affiliations
                Department of Nephrology, Madras Medical College, Chennai, Tamil Nadu, India
                [1 ]Anderson Diagnostics, Chennai, Tamil Nadu, India
                Author notes
                Address for correspondence: Dr. T. Dineshkumar, Department of Nephrology, Madras Medical College, Chennai - 600 003, Tamil Nadu, India. E-mail: dinesh.thaniga@ 123456gmail.com
                Article
                IJN-26-257
                10.4103/0971-4065.160334
                4964685
                27512297
                Copyright: © 2016 Indian Journal of Nephrology

                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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