Kidney Week

Abstract: SA-PO335

Antigen-Specific IgG Subclasses in Primary and Malignancy-Associated Membranous Nephropathy

Session Information

• Glomerular Diseases: Immunology and Inflammation - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Von haxthausen, Franziska, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany

Franziska Von haxthausen,

• Reinhard, Linda, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany

Linda Reinhard,

• Hoxha, Elion, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany

Elion Hoxha,

• Stahl, Rolf A., III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, HH, Germany

Rolf A. Stahl,

Background

The immunologic mechanisms leading to initiation of primary MN are assumed to be different from those in cancer-associated MN, however, the evidence for this proposal has not been systematically evaluated. For decades primary MN was considered to have an IgG4-driven autoimmune genesis, while secondary MN associated with other diseases, most notably cancer, was not linked to IgG4. The identification of the phospholipase A₂ receptor 1 (PLA₂R1) and thrombospondin type-1 domain-containing 7A (THSD7A) as target antigens of autoimmunity in MN now allows a pathogenesis-driven differential diagnosis and may help to better understand the differences between the pathomechanisms of primary and secondary MN. Recent data showing a molecular link between THSD7A expression in tumors and THSD7A-antibody positive MN suggest a similar pathogenesis of malignancy-associated and primary MN.

Methods

In this study we systematically analyzed circulating antigen-specific IgG subclasses in the serum of 76 patients with PLA₂R1-associated MN and 41 patients with THSD7A-associated MN in relationship to concurrent malignancy and disease outcome. All IgG subclasses were analyzed by Western blot. Twenty-three patients in the study had a malignancy-associated MN. Human lung and glomerular protein extracts were analyzed under non-reducing conditions for expression of both PLA₂R1 and THSD7A.

Results

At baseline all 117 patients were positive for IgG4-antibodies against either PLA₂R1 or THSD7A, while IgG3, IgG1 and IgG2-antibodies were found in 87%, 72% and 26% of patients, respectively. There were no differences in the IgG subclass distribution between patients with primary versus cancer-associated MN and no association with disease outcome. Both podocytes and lung bronchioles showed expression of both PLA₂R1 and THSD7A when analyzed by immunofluorescence and Western blot. Every antigen-specific IgG subclass showed identical antigen-binding in both organs and autoantibodies bound the respective antigen only under non-reducing conditions.

Conclusion

We conclude that antigen-specific IgG subclasses do not differentiate between primary and malignancy-associated MN or predict disease prognosis. The data support the view that one common pathway may lead to primary and cancer-associated MN induced by PLA₂R1- or THSD7A-antibodies.

Funding

• Government Support - Non-U.S.