A rare case of renal AHL amyloidosis with marked complement deposition: clinicopathologic and proteomic findings

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, which accounts for approximately 7%. Several studies have demonstrated that complement components can be detected in renal amyloidosis. We report a rare case of renal AHL amyloidosis with marked complement deposition with clinicopathologic and proteomic insights.

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. Kidney biopsy demonstrated Congo red-positive fibrillar deposits with IgG1, κ, and complement (C3/C1q) staining. Electron microscopy revealed non-branching fibrils measuring 8 to 12 nm in diameter. Because marked complement deposition was observed, fibrillary glomerulonephritis (FGN) was considered in the differential diagnosis. However, negative Dna J heat-shock protein family B member 9 immunostaining raised suspicion for amyloidosis. Mass spectrometry identified IgG1 heavy and κ light chains together with serum amyloid P and apolipoprotein E, confirming IgG1-κ-type AHL amyloidosis.

This case illustrates a presentation of AHL amyloidosis with marked complement deposition. Recent study reveals that complement components can be detected in a subset of amyloidosis cases. These features can complicate the differential diagnosis from FGN and highlight the importance of an integrated diagnostic approach combining histopathology, immunostaining, and proteomic analysis. Furthermore, clone-directed therapy targeting the pathogenic plasma cell clone may represent a rational therapeutic strategy for monoclonal immunoglobulin-associated renal disease.