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      Secondary membranous nephropathy in a patient with myasthenia gravis without thymic disease, and partial remission induced by adrenocorticotropic hormone therapy

      case-report

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          Abstract

          Membranous glomerulonephritis is the most common glomerular disease in adults. Its primary form has been characterized with formation of phospholipase A2 receptor antibodies. Malignancy, infections, and autoimmune disorders are the most common causes of secondary membranous glomerulonephritis. We present a case of a 55-year-old African American female who presented with nephrotic range proteinuria and diagnosed with secondary membranous glomerulonephritis based on distinct pathological features on kidney biopsy and absence of serum phospholipase A2 receptor antibodies. She initially underwent extensive workup for malignancies, infections, and common autoimmune disorders which were all negative. Her proteinuria remained resistant to steroid treatment and she was treated with subcutaneous adrenocorticotropic hormone injections. Meanwhile, she was also diagnosed with the anti-muscle specific kinase antibody variant of myasthenia gravis. In literature, there are few case reports of myasthenia gravis as a cause of secondary membranous glomerulonephritis. In our case, the lack of other inciting factors also suggested this association.

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          Most cited references39

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          THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity

          Thrombospondin type I domain-containing 7A (THSD7A) is a known antigenic target of autoantibodies leading to primary membranous glomerulopathy and was reported to account for ~10% of phospholipase A2 receptor (PLA2R)-negative membranous glomerulopathy. It has been proposed that PLA2R and THSD7A autoantibodies are mutually exclusive in membranous glomerulopathy. We validated an immunohistochemical assay to investigate for THSD7A-associated membranous glomerulopathy and utilized it in 258 consecutive native kidney biopsies, which showed membranous glomerulopathy in our laboratory, with the exception of membranous lupus nephritis. Membranous glomerulopathy stained positive for THSD7A-only in 7 (3%) cases, PLA2R-only in 141 (55%) cases, and showed dual positivity for THSD7A and PLA2R in 2 (1%) cases. Serologic testing for antibodies to PLA2R and THSD7A was performed in a subset of these patients. There was 100% correlation between positive THSD7A and/or PLA2R tissue staining and the presence of the corresponding autoantibodies in the serum including the two cases with dual positive THSD7A and PLA2R antibodies. We describe and provide a protocol for detection of THSD7A-associated membranous glomerulopathy in clinical practice. The cases with dual THSD7A and PLA2R positivity show that these autoantibodies are not mutually exclusive. They also emphasize the importance of using a panel-based approach when subtyping membranous glomerulopathy as a patient could conceptually be identified and treated based on anti-PLA2R titers, but still have anti-THSD7A antibodies driving persistent disease.
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            Diagnostic accuracy of PLA2R autoantibodies and glomerular staining for the differentiation of idiopathic and secondary membranous nephropathy: an updated meta-analysis

            The diagnostic performance of M-type phospholipase A2 receptor (PLA2R) autoantibodies and PLA2R glomerular staining in discriminating between idiopathic membranous nephropathy (iMN) and secondary membranous nephropathy (sMN) has not been fully evaluated. We conducted an updated meta-analysis to investigate the accuracy and clinical value of serological anti-PLA2R test and histological PLA2R staining for differentiation iMN from sMN. A total of 19 studies involving 1160 patients were included in this meta-analysis. The overall sensitivity, specificity, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) of serum anti-PLA2R were 0.68 (95% CI, 0.61–074), 0.97 (95% CI, 0.85–1.00), 73.75 (95% CI, 12.56–432.96) and 0.82 (95% CI, 0.78–0.85), respectively, with substantial heterogeneity (I2 = 86.42%). Subgroup analyses revealed the study design, publication type, study origin, assay method might account for the heterogeneity. Additionally, the overall sensitivity, specificity, DOR and AUROC of glomerular PLA2R staining were 0.78 (95% CI, 0.72–0.83), 0.91 (95% CI, 0.75–0.97), 34.70 (95% CI, 9.93–121.30) and 0.84 (95% CI, 0.81–0.87), respectively, without heterogeneity (I2 = 0%). Serological anti-PLA2R testing has diagnostic value, but it must be interpreted in context with patient clinical characteristics and histological PLA2R staining in seronegative patients is recommended.
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              Venous thromboembolism in patients with membranous nephropathy.

              The aims of this study were to determine the frequency of venous thromboembolic events in a large cohort of patients with idiopathic membranous nephropathy and to identify predisposing risk factors.
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                Author and article information

                Journal
                SAGE Open Med Case Rep
                SAGE Open Med Case Rep
                SCO
                spsco
                SAGE Open Medical Case Reports
                SAGE Publications (Sage UK: London, England )
                2050-313X
                08 August 2019
                2019
                : 7
                : 2050313X19869764
                Affiliations
                [1 ]Division of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
                [2 ]Division of Nephrology, Department of Medicine, School of Medicine, University of California, Irvine, Irvine, CA, USA
                [3 ]Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
                [4 ]Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
                Author notes
                [*]Ramy M Hanna, Division of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 700 Tiverton Avenue, Los Angeles, CA 90095, USA. Email: Rhannamd81@ 123456yahoo.com
                Author information
                https://orcid.org/0000-0003-1807-8909
                Article
                10.1177_2050313X19869764
                10.1177/2050313X19869764
                6689923
                735d8ffb-373a-423d-8af3-d9178e9d161c
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 8 February 2019
                : 23 July 2019
                Categories
                Case Report
                Custom metadata
                January-December 2019

                nephrology,neurology,proteinuria,myasthenia gravis,secondary membranous glomerulonephritis,adrenocorticotropic hormone,rituximab

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