Kidney Week

Abstract: PO1539

Non-Pathogenetic THSD7A Antibodies in a Patient with No Membranous Nephropathy

Session Information

• Glomerular Diseases: Clinical Features and Outcomes in Nephrotic Syndromes and Complement-Mediated Diseases
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Reinhard, Linda, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Linda Reinhard, PhD

• Thomas, Cindy, EUROIMMUN Medizinische Labordiagnostika AG, Lubeck, Schleswig-Holstein, Germany

Cindy Thomas,

• Machalitza, Maya, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Maya Machalitza,

• Lattwein, Erik, EUROIMMUN Medizinische Labordiagnostika AG, Lubeck, Schleswig-Holstein, Germany

Erik Lattwein,

• Weiß, Lothar S., Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Lothar S. Weiß,

• Vitu, Jan, Medizinisches Versorgungszentrum Hamburg-Sinstorf der MVZ gGMbH der PHV, Hamburg, Germany

Jan Vitu,

• Wiech, Thorsten, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Thorsten Wiech,

• Stahl, Rolf A., Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Rolf A. Stahl,

• Hoxha, Elion, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Elion Hoxha,

Background

PLA₂R- and THSD7A-antibodies (ab) are considered to be specific for the diagnosis of membranous nephropathy (MN). There is a controversial discussion whether the detection of circulating PLA₂R- or THSD7A-ab is sufficient to diagnose MN, without the need of a kidney biopsy.

Methods

Circulating THSD7A-ab were detected and their specificity evaluated by an indirect immunofluorescence test (IIFT), reducing, non-reducing and native Western blot techniques as well as a live cell assay. The kidney biopsy was investigated by immunohistochemistry and electron microscopy.

Results

A patient presented with high level proteinuria and was tested positive for THSD7A-ab using IIFT. Except for the diagnosis of diabetes mellitus, the medical history of the patient was unremarkable. Because of persistent proteinuria and a decline of kidney function, a kidney biopsy was performed, showing the diagnosis of diabetic nephropathy and excluding MN. A detailed biochemical characterization of the THSD7A-ab was performed to clarify these discrepancies between the serological and histomorphological findings. The circulating THSD7A-ab from the serum of the patient bound to recombinant THSD7A in the IIFT, co-localizing with THSD7A in co-immunofluorescence staining experiments and reacted with purified THSD7A in reducing WB analyses. However, these antibodies did not bind THSD7A derived from human glomerular tissue in any experimental condition (reducing, non-reducing, native). Moreover, the circulating THSD7A-ab did not recognize recombinant THSD7A under native conditions in the native Western blot or live cell assay. In contrast, THSD7A-ab from MN patients recognized native THSD7A in all experiments.

Conclusion

We show for the first time the existence of non-pathogenetic THSD7A-ab, which are not able to bind THSD7A in vivo and can hence not induce MN. Nevertheless, their presence can be detected by different assays, leading to false-positive results for pathogenic circulating THSD7A-ab. In cases of low THSD7A-ab positivity in IIFT, findings from different diagnostic tests such as kidney biopsy, Western blot analyses and live cell assays should be integrated in making a safe diagnosis of THSD7A-ab positive MN.

Funding

• Commercial Support –