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      Membranous nephropathy associated with viral infection

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          Abstract

          Background

          Membranous nephropathy (MN) can be associated with hepatitis infection and less commonly with human immunodeficiency virus (HIV) infection. The significance of anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibodies in this setting is unclear.

          Methods

          We describe the clinical, histopathological and outcome data of 19 patients with MN and hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV infection identified through our renal biopsy database and the association with anti-PLA2R antibodies and anti-THSD7A antibodies.

          Results

          The cohort consisted of 19 patients, 8 male and 11 female, with a median age of 42 years (range 23–74). HBV infection was found in six cases, HCV in four and HIV in nine (two HIV patients had HBV co-infection and one HCV co-infection). PLA2R staining on biopsy was positive in 10/19 patients: 4 with HBV-MN, 3 with HCV-MN and 3 with HIV-MN and circulating anti-PLA2R antibodies were detected in 7/10 cases. THSD7A staining on biopsy was positive in three PLA2R-negative cases, one with HBV-MN and two with HIV-MN. Mean proteinuria was higher in the PLA2R-positive group and the median urinary protein:creatinine ratio (uPCR) was 963 mg/mmol (range 22–2406) compared with the PLA2R-negative group [median uPCR 548 mg/mmol (range 65–1898); P = 0.18 Mann–Whitney]. Spontaneous remission occurred in 6/19 patients and after-treatment remission occurred in 7/11 patients. Renal function was preserved in all but two patients who required haemodialysis 2 and 11 years from diagnosis.

          Conclusions

          We describe a cohort of patients with MN associated with viral infection, including rare cases of HIV-MN with PLA2R and THSD7A positivity. The mechanism of coincidental or viral-related MN needs to be investigated further.

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          Most cited references27

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          M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.

          Idiopathic membranous nephropathy, a common form of the nephrotic syndrome, is an antibody-mediated autoimmune glomerular disease. Serologic diagnosis has been elusive because the target antigen is unknown. We performed Western blotting of protein extracts from normal human glomeruli with serum samples from patients with idiopathic or secondary membranous nephropathy or other proteinuric or autoimmune diseases and from normal controls. We used mass spectrometry to analyze the reactive protein bands and confirmed the identity and location of the target antigen with a monospecific antibody. Serum samples from 26 of 37 patients (70%) with idiopathic but not secondary membranous nephropathy specifically identified a 185-kD glycoprotein in nonreduced glomerular extract. Mass spectrometry of the reactive protein band detected the M-type phospholipase A(2) receptor (PLA(2)R). Reactive serum specimens recognized recombinant PLA(2)R and bound the same 185-kD glomerular protein as did the monospecific anti-PLA(2)R antibody. Anti-PLA(2)R autoantibodies in serum samples from patients with membranous nephropathy were mainly IgG4, the predominant immunoglobulin subclass in glomerular deposits. PLA(2)R was expressed in podocytes in normal human glomeruli and colocalized with IgG4 in immune deposits in glomeruli of patients with membranous nephropathy. IgG eluted from such deposits in patients with idiopathic membranous nephropathy, but not in those with lupus membranous or IgA nephropathy, recognized PLA(2)R. A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA(2)R. PLA(2)R is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that PLA(2)R is a major antigen in this disease. 2009 Massachusetts Medical Society
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            Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy.

            Idiopathic membranous nephropathy is an autoimmune disease. In approximately 70% of patients, it is associated with autoantibodies against the phospholipase A2 receptor 1 (PLA2R1). Antigenic targets in the remaining patients are unknown.
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              • Abstract: not found
              • Article: not found

              PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy.

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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                March 2021
                15 April 2020
                15 April 2020
                : 14
                : 3
                : 876-883
                Affiliations
                [1 ] Renal Department, Imperial College Healthcare NHS Trust , London, UK
                [2 ] Department of Immunology and Inflammation, Centre for Inflammatory Diseases, Imperial College , London, UK
                [3 ] Nephrology Department, Centro Hospitalar e Universitario de Coimbra , Coimbra, Portugal
                Author notes
                Correspondence to: Aikaterini Nikolopoulou; E-mail: Lina.nikolopoulou13@ 123456imperial.ac.uk
                Article
                sfaa026
                10.1093/ckj/sfaa026
                7986439
                33777370
                dba3c990-f5b6-4d6e-bf78-59b5a1f38d5f
                © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 09 September 2019
                : 28 January 2020
                Page count
                Pages: 8
                Funding
                Funded by: National Institute for Health Research, DOI 10.13039/501100000272;
                Funded by: Imperial Biomedical Research Centre, DOI 10.13039/501100013342;
                Funded by: NIHR Biomedical Research Centre;
                Funded by: Imperial College Healthcare NHS Trust, DOI 10.13039/501100000762;
                Funded by: Imperial College London, DOI 10.13039/501100000761;
                Funded by: NHS;
                Funded by: NIHR, DOI 10.13039/100006662;
                Funded by: Department of Health, DOI 10.13039/501100003921;
                Funded by: NIHR Imperial Biomedical Research Centre, DOI 10.13039/501100013342;
                Categories
                Original Articles
                AcademicSubjects/MED00340

                Nephrology
                hepatitis b,hepatitis c,hiv,membranous nephropathy,pla2r,thsd7a
                Nephrology
                hepatitis b, hepatitis c, hiv, membranous nephropathy, pla2r, thsd7a

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