Validation of phospholipase A2 receptor direct immunofluorescence staining in the diagnosis of primary membranous glomerulonephritis

Pei Dai; David Campbell; Suzanne Culican; David A Brown; Karen Byth; Pravin Hissaria; Ruth Ninnes; Brian Nankivell; Ming-Wei Lin

doi:10.1016/j.pathol.2020.04.003

Validation of phospholipase A₂ receptor direct immunofluorescence staining in the diagnosis of primary membranous glomerulonephritis

Pathology. 2020 Aug;52(5):546-551. doi: 10.1016/j.pathol.2020.04.003. Epub 2020 Jun 18.

Authors

Pei Dai¹, David Campbell², Suzanne Culican², David A Brown³, Karen Byth⁴, Pravin Hissaria⁵, Ruth Ninnes⁵, Brian Nankivell⁶, Ming-Wei Lin³

Affiliations

¹ Department of Immunopathology, New South Wales Health Pathology-Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, NSW, Australia. Electronic address: pei.dai@gmail.com.
² Department of Immunopathology, New South Wales Health Pathology-Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, NSW, Australia.
³ Department of Immunopathology, New South Wales Health Pathology-Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, NSW, Australia; Centre for Allergy and Immunology Research, Westmead Institute, Sydney, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
⁴ Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Research and Education Network, Westmead Hospital, Sydney, NSW, Australia.
⁵ SA Pathology, Adelaide, SA, Australia.
⁶ Department of Renal Medicine, Westmead Hospital, Sydney, NSW, Australia.

PMID: 32564921
DOI: 10.1016/j.pathol.2020.04.003

Abstract

Distinguishing between primary and secondary subtypes of membranous glomerulonephritis (MGN) is critical for its clinical management. We prospectively compared direct immunofluorescence (DIF) staining for phospholipase A₂ receptor (PLA₂R) on frozen renal biopsy with the presence of detectable serum PLA₂R antibody assessed by enzyme linked immunosorbent assay (ELISA) in the diagnosis of primary MGN. Forty-six patients with biopsy-proven MGN were enrolled from April 2017 to June 2019 with 31/46 (67.4%) being primary and 15/46 (32.6%) being secondary as determined by comprehensive clinical assessment. This is currently deemed to be the gold standard for distinguishing primary from secondary MGN. Amongst the 31 primary MGN patients, 24/31 were positive on PLA₂R DIF staining compared to 18/31 being positive on the PLA₂R ELISA (p=0.03). Amongst the 15 secondary MGN patients, 1/15 was positive on PLA₂R DIF compared to 0/15 on PLA₂R ELISA (p=1.0). In conclusion, the presence of PLA₂R staining on DIF demonstrated superior sensitivity and similar specificity compared to the detection of circulating PLA₂R antibodies by ELISA in the diagnosis of primary MGN in a cohort of 46 patients with biopsy-proven MGN. We suggest that DIF should be considered as part of routine work-up in all newly diagnosed cases of MGN.

Keywords: Phospholipase A(2) receptor antibody; direct immunofluorescence; frozen renal tissue; membranous glomerulonephritis; membranous nephropathy; phospholipase A(2) receptor staining.

MeSH terms

Adult
Aged
Autoantibodies / blood
Enzyme-Linked Immunosorbent Assay / methods
Female
Fluorescent Antibody Technique, Direct / methods*
Glomerulonephritis, Membranous / diagnosis*
Glomerulonephritis, Membranous / metabolism
Glomerulonephritis, Membranous / pathology
Humans
Kidney / metabolism*
Kidney / pathology
Male
Middle Aged
Receptors, Phospholipase A2 / immunology
Receptors, Phospholipase A2 / metabolism*

Substances

Autoantibodies
Receptors, Phospholipase A2