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

Autor: Reinhard L; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany., Thomas C; Institute of Experimental Immunology, EUROIMMUN AG, Lübeck, Germany., Machalitza M; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany., Lattwein E; Institute of Experimental Immunology, EUROIMMUN AG, Lübeck, Germany., Weiss LS; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany., Vitu J; Medizinisches Versorgungszentrum Hamburg-Sinstorf der MVZ gGmbH der PHV, Hamburg, Germany., Wiech T; Institute of Pathology, Section Nephropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany., Stahl RAK; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany., Hoxha E; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. ehoxha@uke.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Aug 10; Vol. 11 (1), pp. 16188. Date of Electronic Publication: 2021 Aug 10.
DOI: 10.1038/s41598-021-94921-y
Abstrakt: Membranous nephropathy (MN) is an autoimmune disease caused by autoantibodies against the podocyte antigens phospholipase A 2 receptor 1 (PLA 2 R1) 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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