Method and reagents for diagnosing membranous nephropathy

Patent metadata

Field	Value
Publication number	US-12442823-B2
Application number	US-202117457279-A
Country	US
Kind code	B2
Filing date	Dec 2, 2021
Priority date	Dec 11, 2020
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

Abstract

Provided are a diagnostically useful carrier coated with a recombinant polypeptide comprising SEQ ID NO: 1, an isolated autoantibody binding specifically to a polypeptide having SEQ ID NO: 1, a kit comprising the carrier, a method for the diagnosis of a membranous nephropathy (MN) that includes detecting the presence or absence of an autoantibody binding specifically to a polypeptide having SEQ ID NO: 1 in a liquid sample comprising antibodies from a subject, a use of an autoantibody binding specifically to a polypeptide having SEQ ID NO: 1 or a polypeptide comprising SEQ ID NO: 1, and a aqueous solution comprising an autoantibody binding specifically to a polypeptide having SEQ ID NO: 1.

First claim

The invention claimed is:

1. A method for detecting an autoantibody to EXT2 or to a complex of EXT2 and EXT1 from a subject having or suspected of having membranous nephropathy, comprising:
detecting the presence of an autoantibody binding specifically to a polypeptide having SEQ ID NO: 1 or to a complex comprising a polypeptide having SEQ ID NO: 1 and a polypeptide having SEQ ID NO: 2 or a variant thereof, in a liquid sample comprising antibodies from a subject having or suspected of having membranous nephropathy.

2. The method according to claim 1 , wherein the detecting comprises employing a diagnostically useful carrier coated with a recombinant polypeptide comprising SEQ ID NO: 1 or a complex comprising a polypeptide comprising SEQ ID NO: 1 and a polypeptide comprising SEQ ID NO: 2, wherein the carrier is selected from the group consisting of a bead, a test strip, a microtiter plate, a membrane, a lateral flow device, a glass surface, a slide for microscopy, a microarray, and a biochip.

3. The method according to claim 2 , wherein the diagnostically useful carrier further comprises one or more recombinant polypeptides selected from the group consisting of a polypeptide comprising SEQ ID NO: 2, a polypeptide comprising SEQ ID NO: 3, a polypeptide comprising SEQ ID NO: 4, a polypeptide comprising SEQ ID NO: 5, and a polypeptide comprising SEQ ID NO: 6.

4. The method according to claim 3 , wherein any immobilized polypeptide is expressed by a cell immobilized on the diagnostically useful carrier or is a recombinant or isolated polypeptide immobilized on the carrier.

5. The method according to claim 4 , wherein any immobilized polypeptide is expressed by a cell immobilized on the diagnostically useful carrier and the diagnostically useful carrier further comprises a mock-transfected cell.

6. The method according to claim 2 , wherein an autoantibody binding specifically to SEQ ID NO: 1 is bound to the polypeptide comprising SEQ ID NO: 1 and optionally a secondary antibody comprising a label.

7. The method according to claim 1 wherein the detecting comprises employing a diagnostically useful carrier; and
one or more components selected from the group consisting of means for detecting an autoantibody binding specifically to the polypeptide having SEQ ID NO: 1 or the complex, means for capturing an autoantibody binding specifically to the polypeptide having SEQ ID NO: 1 or to the complex, a washing buffer, a mounting medium, dilution buffer, a positive control, a negative control, a calibrator, and a recombinant polypeptide comprising SEQ ID NO: 1, optionally in complex with a polypeptide comprising SEQ ID NO: 2.

8. The method according to claim 1 , wherein the sample is whole blood, serum, and/or plasma.

9. The method according to claim 1 , further comprising:
detecting the presence or absence of an autoantibody selected from the group consisting of an autoantibody binding specifically to an autoantibody binding specifically to a polypeptide having SEQ ID NO: 2, an autoantibody binding specifically to a polypeptide having SEQ ID NO: 3, an autoantibody binding specifically to a polypeptide having SEQ ID NO: 4, an autoantibody binding specifically to a polypeptide having SEQ ID NO: 5 and an autoantibody binding specifically to a polypeptide having SEQ ID NO: 6.

10. The method according to claim 1 , further comprising removing an autoantibody to the polypeptide having SEQ ID NO: 1 or to the complex, from blood, with a device, wherein the device comprises:
a carrier coated with the polypeptide comprising SEQ ID NO: 1 or the complex.

11. The method according to claim 1 , further comprising an ex vivo method for removing an autoantibody to the polypeptide having SEQ ID NO: 1 or the complex, from blood, the method comprising:
contacting the blood to a carrier coated with the polypeptide having SEQ ID NO: 1 or the complex.

12. The method according to claim 7 , wherein the means for detecting the autoantibody binding specifically to the polypeptide having SEQ ID NO: 1 or to the complex is selected from the group consisting of a secondary antibody or the polypeptide comprising SEQ ID NO: 1.

13. The method according to claim 1 , comprising detecting the presence or absence of an autoantibody binding specifically to a complex comprising a polypeptide having SEQ ID NO: 1 and a polypeptide having SEQ ID NO: 2.

14. The method according to claim 1 , comprising detecting the presence or absence of an autoantibody binding specifically to SEQ ID NO: 1.

Assignees

• Euroimmun Medizinische Labordiagnostika Ag

Inventors

• Dettmann Inga-Madeleine
• Mindorf Swantje
• Probst Christian

Classifications

• G01N2800/347

  Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy · CPC title

• G01N33/6857

  Antibody fragments · CPC title

• G01N33/564 Primary

  for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9} · CPC title

• G01N33/6893 Primary

  related to diseases not provided for elsewhere · CPC title

• G01N33/554

  the carrier being a biological cell or cell fragment, e.g. bacteria, yeast cells · CPC title