A 28-year-old woman with SLE develops hematuria, RBC casts, proteinuria of 3.2 g/day and rising serum creatinine. Renal biopsy shows diffuse proliferative changes with 'wire loop' deposits; immunofluorescence reveals full-house staining (IgG, IgM, IgA, C3, C1q). Electron microscopy shows subendothelial and mesangial deposits with occasional subepithelial ('humps'). Which ISN/RPS class does this represent, and what makes the 'wire loop' lesion pathognomonic of severe disease?

• A ISN/RPS Class III; wire loop lesions represent focal fibrinoid necrosis of the glomerular basement membrane seen only in necrotizing vasculitis
• B ISN/RPS Class V; wire loop deposits represent membranous-pattern subepithelial IgG deposits forming spikes on silver stain
• C ISN/RPS Class II; wire loops are mesangial deposits causing mesangial expansion with no endothelial involvement
• D ISN/RPS Class IV; wire loop lesions are massive subendothelial immune complex deposits that thicken and rigidify the GBM, seen on light microscopy as PAS-positive hyaline thickening mimicking wire-loops; their presence indicates high antigen-antibody burden, complement activation, and severe endocapillary proliferation ✓

Explanation

This presentation — diffuse proliferative changes with full-house immunofluorescence, subendothelial and mesangial deposits, and wire-loop lesions — is diagnostic of ISN/RPS Class IV lupus nephritis (diffuse proliferative). Wire-loop lesions result from massive subendothelial immune complex (predominantly IgG with complement) deposits that expand the inner aspect of the GBM to create a rigid, glassy, refractile appearance on PAS and silver stains. They indicate very high immune complex burden and severe complement consumption, correlating with the worst renal prognosis among LN classes and requiring aggressive therapy (cyclophosphamide or mycophenolate + corticosteroids).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.