A case of AHL amyloidosis with prominent complement deposition, differentiated from fibrillary glomerulonephritis by mass spectrometry

Background Amyloidosis comprises a heterogeneous group of diseases characterized by extracellular deposition of β-pleated-sheet fibrillar proteins that cause progressive organ dysfunction. Among immunoglobulin-related amyloidosis, combined heavy- and light-chain (AHL) amyloidosis is extremely rare and is not formally included in the current International Society of Amyloidosis classification. Although complement deposition is typically minimal in amyloidosis, it is a characteristic feature of fibrillary glomerulonephritis (FGN). We report a case of renal AHL amyloidosis with unexpectedly prominent complement deposition, presenting a diagnostic challenge between amyloidosis and FGN. Case presentation: A 76-year-old woman with a five-year history of microscopic hematuria developed mild renal dysfunction (serum creatinine 1.05 mg/dL) and proteinuria (0.95 g/day). Physical and serologic evaluations showed no evidence of systemic amyloidosis or autoimmune disease. Serum and urine immunofixation detected an IgG-κ M-protein, and bone marrow findings were consistent with monoclonal gammopathy of undetermined significance. Renal biopsy revealed amorphous periodic acid–Schiff-positive, Congo red–positive deposits with apple-green birefringence in the mesangium, vessel walls, and interstitium. Immunofluorescence demonstrated IgG1 (2+), κ (2+), and C3/C1q (2+) staining, with negative λ staining. Electron microscopy revealed non-branching fibrils measuring 8 to 12 nm in diameter. Mass spectrometry identified IgG1 heavy and κ light chains together with serum amyloid P and apolipoprotein E, while Dna J heat-shock protein family B member 9 (DNAJB9) was absent, confirming IgG1-κ-type AHL amyloidosis. Conclusions This case illustrates an atypical presentation of AHL amyloidosis with marked complement deposition, a feature more commonly associated with FGN. The coexistence of amyloid signature proteins and complement components suggests potential immunologic overlap among fibrillar monoclonal gammopathy of renal significance (MGRS) lesions. Accurate differentiation between amyloidosis and FGN requires an integrated diagnostic approach incorporating Congo red staining, DNAJB9 immunostaining, and laser microdissection–mass spectrometry. Recognition of such overlapping patterns is essential for appropriate classification and management of monoclonal immunoglobulin–associated renal diseases.