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PLA2R Immunohistochemistry Staining in Membranous Glomerulopathy: A Challenging Stain to Interpret But a Potentially
Rachele Del Sordo1, Carla Covarelli1, Rachele Brugnano2
1Department of Experimental Medicine, Section of Anatomic Pathology and Histology, Medical School, University of Perugia.
Abstract:
Circulating autoantibodies to phospholipase A2 receptor (PLA2R-Ab) are detected in >70% of patients with primary membranous glomerulonephritis (MGN). Detection of PLA2R antigen in renal tissue, with immunohistochemistry (PLA2R IHC), strongly correlates with serum PLA2R-Ab, although it is more sensitive. As PLA2R IHC in literature has no univocal interpretation, we suggest reliable criteria for a standard approach for the assessment of immunostaining for differential diagnosis between primary and secondary MGN. We analyzed PLA2R IHC expression in 40 biopsies of patients with MGN and serum PLA2R-Ab titer at the time of biopsy. We carefully evaluated, at high magnification, the immunostaining pattern and distribution, regardless of intensity, in capillary loops, mesangium, and podocytes of all glomeruli.We defined, adopting this approach, positive stain when a granular pattern, coarse and/or fine, diffuse or focal, and global or segmental were observed. Negative stain was defined by mesangial staining, when there was a dirty pattern, or a peripheral staining of capillary loops with a smoky linear pattern. Podocytes showed homogenous cytoplasmatic stain both in positive and negative cases and in external negative controls. We found PLA2R IHC and serum PLA2R-Ab positivity in early-middle stage MGN compared with advanced stage more frequently. Correct stratification of patients with MGN needs PLA2R-Ab detection in serum and renal tissue. PLA2R IHC test, although a challenging stain, can be an easy diagnostic tool but requires reliable interpretation keys for a standard approach to the assessment of immunostaining.
Insights
Phospholipase A2 receptor (PLA2R) autoantibodies in serum and kidney biopsies are key for diagnosing primary membranous glomerulonephritis (MGN). Standardized interpretation of PLA2R immunohistochemistry (IHC) aids differential diagnosis.
Area of Science:
- Nephrology
- Immunopathology
- Diagnostic Pathology
Background:
- Circulating autoantibodies to phospholipase A2 receptor (PLA2R-Ab) are present in over 70% of primary membranous glomerulonephritis (MGN) patients.
- Renal tissue detection of PLA2R antigen via immunohistochemistry (PLA2R IHC) correlates with serum PLA2R-Ab but offers higher sensitivity.
- Existing PLA2R IHC interpretations lack standardization, hindering differential diagnosis between primary and secondary MGN.
Purpose of the Study:
- To establish reliable criteria for assessing PLA2R IHC staining.
- To standardize the interpretation of PLA2R IHC for differential diagnosis in MGN.
- To correlate PLA2R IHC findings with serum PLA2R-Ab levels and disease stage.
Main Methods:
- Analysis of PLA2R IHC expression in 40 kidney biopsies from MGN patients with concurrent serum PLA2R-Ab titers.
- Detailed evaluation of immunostaining patterns and distribution (capillary loops, mesangium, podocytes) at high magnification.
- Definition of positive (granular, coarse/fine, diffuse/focal, global/segmental) and negative (mesangial, dirty pattern, peripheral smoky linear) staining criteria.
Main Results:
- PLA2R IHC and serum PLA2R-Ab positivity were more frequent in early-to-middle stage MGN compared to advanced stages.
- Specific granular patterns in capillary loops were defined as positive PLA2R IHC.
- Homogenous cytoplasmic staining in podocytes was observed in both positive and negative cases and controls.
Conclusions:
- Accurate stratification of MGN patients requires both serum and renal tissue PLA2R-Ab detection.
- PLA2R IHC, despite being a challenging stain, can be a valuable diagnostic tool with standardized interpretation keys.
- Established criteria facilitate a consistent approach to PLA2R IHC assessment for improved MGN diagnosis.
