2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Immunology of membranous nephropathy

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Accounting for about 20 to 50% of cases of primary nephrotic syndrome, membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. A rat model created nearly 60 years ago to research the primary MN disorder, Heymann nephritis, has provided us with a plethora of important information. Recently, our knowledge about MN has dramatically progressed. Heymann nephritis and human MN are now known to share a high degree of similarity in pathogenesis. This review summarizes our current understanding of MN pathogenesis while focusing particularly on the immunological aspects.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          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.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Identification of a major epitope recognized by PLA2R autoantibodies in primary membranous nephropathy.

              Phospholipase A2 receptor 1 (PLA2R) is a target autoantigen in 70% of patients with idiopathic membranous nephropathy. We describe the location of a major epitope in the N-terminal cysteine-rich ricin domain of PLA2R that is recognized by 90% of human anti-PLA2R autoantibodies. The epitope was sensitive to reduction and SDS denaturation in the isolated ricin domain and the larger fragment containing the ricin, fibronectin type II, first and second C-type lectin domains (CTLD). However, in nondenaturing conditions the epitope was protected against reduction in larger fragments, including the full-length extracellular region of PLA2R. To determine the composition of the epitope, we isolated immunoreactive tryptic fragments by Western blotting and analyzed them by mass spectrometry. The identified peptides were tested as inhibitors of autoantibody binding to PLA2R by surface plasmon resonance. Two peptides from the ricin domain showed strong inhibition, with a longer sequence covering both peptides (31-mer) producing 85% inhibition of autoantibody binding to PLA2R. Anti-PLA2R antibody directly bound this 31-mer peptide under nondenaturing conditions and binding was sensitive to reduction. Analysis of PLA2R and the PLA2R-anti-PLA2R complex using electron microscopy and homology-based representations allowed us to generate a structural model of this major epitope and its antibody binding site, which is independent of pH-induced conformational change in PLA2R. Identification of this major PLA2R epitope will enable further therapeutic advances for patients with idiopathic membranous nephropathy, including antibody inhibition therapy and immunoadsorption of circulating autoantibodies.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Writing – Original Draft Preparation
                Role: ConceptualizationRole: Supervision
                Role: ConceptualizationRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                24 May 2019
                2019
                : 8
                : F1000 Faculty Rev-734
                Affiliations
                [1 ]Division of Nephrology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [2 ]Nakayamadera Imai Clinic, Takarazuka, Hyōgo, Japan
                Author notes

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0003-4313-2911
                https://orcid.org/0000-0002-8858-632X
                Article
                10.12688/f1000research.17589.1
                6537914
                31168358
                e1267293-8a8a-4c32-bb83-09d486b64fd1
                Copyright: © 2019 Akiyama S et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 May 2019
                Funding
                Funded by: Ministry of Health, Labour and Welfare
                Funded by: Japan Agency for Medical Research and Development
                Award ID: JP18ek0109354
                This work was supported by the Japan Agency for Medical Research and Development [JP18ek0109354] and a Grant-in-Aid for Intractable Renal Diseases Research, Research on rare and intractable diseases, Health and Labour Sciences Research Grants [H29-nanchi(nan)-ippan-017] from the Ministry of Health, Labour and Welfare of Japan.
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles

                nep,pla2r,thsd7a,epitope spreading,heymann nephritis,membranous nephropathy,podocyte

                Comments

                Comment on this article