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      Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies.

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          Abstract

          Autoantibody formation directed against phospholipase A2 receptor (PLA2R)1 is the underlying etiology in most cases of primary membranous glomerulopathy. This new understanding of the pathogenesis of primary membranous is in the process of transforming the way the disease is diagnosed. We validated an indirect immunofluorescence assay to examine PLA2R1 in renal biopsies utilizing a commercially available antibody and standard indirect immunofluorescence. Using this assay, we examined a total of 165 cases of membranous glomerulopathy including 85 primary and 80 secondary. We found tissue staining for PLA2R1 to have a sensitivity of 75% (95% CI 65-84%) and a specificity of 83% (95% CI 72-90%) for primary membranous glomerulopathy. Hepatitis C virus was the secondary etiology with the most number of cases staining positive for PLA2R1 (7/11, 64%) followed by sarcoidosis (3/4, 75%) and neoplasm (3/12, 25%). Autoimmune etiologies showed rare PLA2R1-positive staining (1/46, 2%). All cases of secondary membranous glomerulopathy with positive PLA2R1 showed IgG4-predominant staining, which is typically associated with primary membranous glomerulopathy. This IgG4 predominance raises the possibility that these cases are more pathogenically related to primary membranous glomerulopathy than secondary. We present the largest case series to date examining PLA2R1 involvement in membranous glomerulopathy utilizing a technique that is readily adoptable by most renal pathology laboratories.

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          Author and article information

          Journal
          Mod. Pathol.
          Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
          1530-0285
          0893-3952
          May 2013
          : 26
          : 5
          Affiliations
          [1 ] Nephropath, Nephropathology Associates, Little Rock, AR 72211, USA. Chris.larsen@nephropath.com
          Article
          modpathol2012207
          10.1038/modpathol.2012.207
          23196797
          1a1281b5-d21c-45d3-bf73-9712ed242baf
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