Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy

Abstract Membranous nephropathy (MN) is an autoimmune disease caused by autoantibodies against the podocyte antigens phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain containing protein 7A (THSD7A) in 80% and 2–3% of patients, respectively. THSD7A antibodies are considered to be...

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Autores principales:	Linda Reinhard, Cindy Thomas, Maya Machalitza, Erik Lattwein, Lothar S. Weiss, Jan Vitu, Thorsten Wiech, Rolf A. K. Stahl, Elion Hoxha
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7cb5f316a0974a24915ddcfd77d0a653
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spelling	oai:doaj.org-article:7cb5f316a0974a24915ddcfd77d0a6532021-12-02T18:50:49ZCharacterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy10.1038/s41598-021-94921-y2045-2322https://doaj.org/article/7cb5f316a0974a24915ddcfd77d0a6532021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94921-yhttps://doaj.org/toc/2045-2322Abstract Membranous nephropathy (MN) is an autoimmune disease caused by autoantibodies against the podocyte antigens phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain containing protein 7A (THSD7A) in 80% and 2–3% of patients, respectively. THSD7A antibodies are considered to be pathogenic and highly specific for MN patients. Using an indirect immunofluorescence test (IIFT) we detected THSD7A-antibodies (titre 1:10) in the serum of a patient with high proteinuria who, however, in the kidney biopsy was diagnosed with diabetic nephropathy and MN was excluded as a possible cause of proteinuria. Different immunofluorescence assays and Western blot techniques using recombinant THSD7A (rTHSD7A) or THSD7A from different human tissues revealed that the circulating THSD7A-autoantibodies were only of the IgG3 subclass. The patient serum reacted exclusively with rTHSD7A and only when the antigen was present in reducing Western blot conditions, or on formaldehyde-fixed cells for the IIFT. Our findings show for the first time the existence of circulating THSD7A-antibodies recognizing denatured/reduced rTHSD7A, which do not react with glomerular THSD7A in vivo and are thus presumptively non-pathogenic. As a consequence, kidney biopsy or Western blot analyses of THSD7A under non-reducing conditions should be performed to confirm the diagnosis of THSD7A-associated MN, especially in cases with low THSD7A-antibody levels in the IIFT.Linda ReinhardCindy ThomasMaya MachalitzaErik LattweinLothar S. WeissJan VituThorsten WiechRolf A. K. StahlElion HoxhaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Linda Reinhard Cindy Thomas Maya Machalitza Erik Lattwein Lothar S. Weiss Jan Vitu Thorsten Wiech Rolf A. K. Stahl Elion Hoxha Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy
description	Abstract Membranous nephropathy (MN) is an autoimmune disease caused by autoantibodies against the podocyte antigens phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain containing protein 7A (THSD7A) in 80% and 2–3% of patients, respectively. THSD7A antibodies are considered to be pathogenic and highly specific for MN patients. Using an indirect immunofluorescence test (IIFT) we detected THSD7A-antibodies (titre 1:10) in the serum of a patient with high proteinuria who, however, in the kidney biopsy was diagnosed with diabetic nephropathy and MN was excluded as a possible cause of proteinuria. Different immunofluorescence assays and Western blot techniques using recombinant THSD7A (rTHSD7A) or THSD7A from different human tissues revealed that the circulating THSD7A-autoantibodies were only of the IgG3 subclass. The patient serum reacted exclusively with rTHSD7A and only when the antigen was present in reducing Western blot conditions, or on formaldehyde-fixed cells for the IIFT. Our findings show for the first time the existence of circulating THSD7A-antibodies recognizing denatured/reduced rTHSD7A, which do not react with glomerular THSD7A in vivo and are thus presumptively non-pathogenic. As a consequence, kidney biopsy or Western blot analyses of THSD7A under non-reducing conditions should be performed to confirm the diagnosis of THSD7A-associated MN, especially in cases with low THSD7A-antibody levels in the IIFT.
format	article
author	Linda Reinhard Cindy Thomas Maya Machalitza Erik Lattwein Lothar S. Weiss Jan Vitu Thorsten Wiech Rolf A. K. Stahl Elion Hoxha
author_facet	Linda Reinhard Cindy Thomas Maya Machalitza Erik Lattwein Lothar S. Weiss Jan Vitu Thorsten Wiech Rolf A. K. Stahl Elion Hoxha
author_sort	Linda Reinhard
title	Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy
title_short	Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy
title_full	Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy
title_fullStr	Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy
title_full_unstemmed	Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy
title_sort	characterization of thsd7a-antibodies not binding to glomerular thsd7a in a patient with diabetes mellitus but no membranous nephropathy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7cb5f316a0974a24915ddcfd77d0a653
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Characterization of THSD7A-antibodies not binding to glomerular THSD7A in a patient with diabetes mellitus but no membranous nephropathy

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