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

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 auto...

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Main Authors: Larsen, Christopher P, Cossey, L Nicholas, Beck, Laurence H
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820679/
id pubmed-4820679
recordtype oai_dc
spelling pubmed-48206792016-04-17 THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity Larsen, Christopher P Cossey, L Nicholas Beck, Laurence H Original Article 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. Nature Publishing Group 2016-04 2016-02-05 /pmc/articles/PMC4820679/ /pubmed/26847174 http://dx.doi.org/10.1038/modpathol.2016.32 Text en Copyright © 2016 Official journal of the United States and Canadian Academy of Pathology http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Larsen, Christopher P
Cossey, L Nicholas
Beck, Laurence H
spellingShingle Larsen, Christopher P
Cossey, L Nicholas
Beck, Laurence H
THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity
author_facet Larsen, Christopher P
Cossey, L Nicholas
Beck, Laurence H
author_sort Larsen, Christopher P
title THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity
title_short THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity
title_full THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity
title_fullStr THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity
title_full_unstemmed THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity
title_sort thsd7a staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity
description 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.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820679/
_version_ 1613562189627523072

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