Autoantibodies Targeting Complement Regulating Factors Induced C3 Glomerulopathy Resambling C4 Dense Deposit Disease:...

Dense deposit disease (DDD), a subgroup of C3 glomerulopathy, is a rare glomerular disease characterised histologically by predominant C3 staining on immunofluorescence microscopy along with intramembranous osmiophilic dense deposits. C4 DDD is a recently identified form of complement-mediated glomerulonephritis, characterised by intense C4d staining with minimal or absent staining for C3 and immunoglobulin, and dense deposits along the glomerular basement membrane. We present a 27-year-old female patient who exhibited proteinuria during pregnancy. Following delivery, the patient continued to experience persistent non-nephrotic-range proteinuria, along with microscopic hematuria and dramatically decreased serum C3 level, while maintaining preserved renal function. Renal biopsy revealed mesangial proliferative glomerulonephritis with a focal membranoproliferative glomerulonephritis pattern by light microscopy. Electron microscopy demonstrated high-density banded deposits in the glomerular basement membrane, while immunofluorescence exhibited negative C3c and immunoglobulin staining. Immunohistochemical analysis showed diffuse expression of C3d and C4d in the capillary loops, mesangial region, focal tubular basement membrane, and focal arteriolar wall. Further investigation revealed elevated circulating levels of autoantibodies against complement factor H and the C3 convertase. Mass spectrometry confirmed that C3 was the predominant component of the deposits. Ultimately, this patient was diagnosed as DDD mediated by complement factor H autoantibodies and C3 nephritic factor.