Weakened IgG4 Staining and Positive PLA2R staining Indicate Resolving Primary Membranous Glomerulopathy (MGN)

Abstract

Introduction/Objective IgG4 related disease, a systemic autoimmune inflammatory disorders, can be identified by high% of IgG4 positive plasma cells, thus IgG4 staining in paraffin embedded tissue is widely available in the most of pathology labs. IgG4 staining has been found useful to identify primary MGN (PLA2R and/or THSD7A positive) by others and us. This study was to scrutinize the findings of primary vs secondary MGN needed for IgG4 staining as a screening tool in our renal pathology practice over pasts 5 years Methods/Case Report IgG4 staining in paraffin embedded tissue was performed in 45 primary MGN and 43 secondary MGN after the clinical history was reviewed and a possibility of primary MGN cannot be excluded. In addition, both groups of cases were also stained for PLA2R. Detail correlation with clinical history was analyzed. Results (if a Case Study enter NA) Totally 82 % (37/45) of primary MGN was found diffuse positive for IgG4 staining at 2+ intensity in the glomeruli. Seven out of eight remaining primary MGN cases with either negative or weak IgG4 stained MGN were found to have diffuse resolving features by electron microscopy but there was still positive PLA2R staining in the glomeruli. All secondary MGN were stained negatively for both IgG4 and PLA2R and we found that etiologies of the secondary MGN included membranous lupus nephritis, infection, GVHD, or variants of cancers. Conclusion Our data indicate that IgG4 staining along (without IgG1-3 staining) is a reliable screening tool to confirm the majority of primary MGN vs secondary MGN in paraffin embedded tissue. As both PLA2R+ and THSD7A+ primary MGN are both IgG4 related, the IgG4 staining may potentially represent a wider range of scope in identifying primary MGN. In addition, negative/weak IgG4 staining in PLA2R-positive MGN most likely represents a primary MGN with resolving features.