Abstract: TH-PO117

Serological and Immunohistological Characteristics of Membranous Nephropathy in Children

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Dettmar, Anne Katrin, University Medical Center Hamburg- Eppendorf, Hamburg, Germany
  • Wiech, Thorsten, University Medical Center Hamburg Eppendorf, Hamburg, Germany
  • Kemper, Markus J, Asklepios Nord-Heidberg, Hamburg, Germany
  • Oh, Jun, University Medical Center Hamburg- Eppendorf, Hamburg, Germany
  • Stahl, Rolf A., University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Hoxha, Elion, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Group or Team Name

  • Pediatric MN Study Group
Background

In adult patients with membranous nephropathy (MN) phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain containing 7A (THSD7A) are the target antigens in 80% and 2-3% of patients, respectively. In children MN is less common and two more antigens are involved in disease development: neutral endopeptidase (NEP) and cationic bovine serum albumin (cBSA). In this study we performed a clinical, serological and immunhistological characterization of MN in children.

Methods

Twelve children with biopsy-proven MN were included. We analyzed the sera for PLA2R1, THSD7A, NEP and cBSA-Antibodies (Ab). Clinical data and blood samples were evaluated every three months. Immunohistochemical analyses for all antigens and IgG subclasses were performed in five biopsies. The median follow-up time was 24 months.

Results

Six (50%) children had a PLA2R1-associated MN. There were no antibodies against THSD7A, NEP or cBSA in any of the sera. To detect further potential antigens, all sera were analyzed by Western blot against human glomerular extracts, showing no further specific reactions. Immunohistochemical analyses of renal biopsies identified no THSD7A, NEP or cBSA-associated case in our cohort. Two biopsies from PLA2R1-associated patients showed enhanced staining for PLA2R1, but not for the other antigens. Both biopsies were positive for IgG2 and IgG4. In contrast, all three biopsies from patients with non-PLA2R1-associated MN stained negative for IgG2 and IgG4. IgG1 and IgG3 staining was not different between PLA2R1- and non-PLA2R1-associated MN cases. Four PLA2R1-Ab positive and five PLA2R1-Ab negative patients had a remission of proteinuria. In PLA2R1-associated cases remission was preceded by decline of PLA2R1-Ab levels. In one patient a relapse of proteinuria occurred and was preceded by PLA2R1-Ab reappearance in serum.

Conclusion

PLA2R1-Ab levels are associated with disease activity and outcome in pediatric MN. PLA2R1-associated MN is a common form of pediatric MN, however, in a considerable number of patients the pathogenesis of the disease remains unclear.

Funding

  • Private Foundation Support