A Unique Case of Membranous Lupus Nephritis Identified After Pronase Digestion

Membranous nephropathy (MN) is a common etiology of nephrotic syndrome (NS) in Caucasian adults. With treatment strategies heavily dependent on differentiating between primary versus secondary MN, tissue diagnosis remains paramount in the setting of indeterminant serological studies and remains the gold standard. Direct immunofluorescence on frozen sections remains standard practice, though with inadequate kidney tissue, antigen retrieval with proteases on formalin-fixed paraffin-embedded tissue can be a viable alternative for direct immunofluorescence. We report a patient who presented with nephrotic syndrome, indeterminant serological workup including primary antigen phospholipase-2 receptor antibody (PLA₂R). Histology revealed a membranous pattern of injury with a negative standard panel of immunocomplex deposits on direct immunofluorescence. Upon re-examination of paraffin-embedded tissue via protease processing, Immunofluorescence unmasked membranous lupus nephritis. This case highlights the possibility of negative direct immunofluorescence on viable frozen tissue which is unmasked after protease treatment on formalin-fixed paraffin-embedded tissue sample revealing immunocomplex deposits.