IMMUNOGLOBULIN G4-RELATED TUBULOINTERSTITIAL NEPHRITIS COEXISTING WITH RENAL AA AMYLOIDOSIS: A RARE CASE REPORT

Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated condition characterized by organ enlargement, dense infiltration of IgG4-positive plasma cells, and storiform fibrosis. The kidneys are often involved as IgG4-related tubulointerstitial nephritis (IgG4-TIN). Amyloid A (AA) amyloidosis results from extracellular deposition of serum amyloid A protein and frequently affects the kidneys, leading to progressive renal dysfunction. Although AA amyloidosis commonly arises from chronic inflammatory conditions, its coexistence with IgG4-RD is extremely rare. We report a unique case of IgG4-RD with IgG4-TIN and concurrent renal AA amyloidosis, representing, to our knowledge, the first such combination reported.

A 56-year-old Chinese man with chronic kidney disease, anemia, and systemic lymphadenopathy underwent comprehensive clinical, laboratory, and pathological evaluation. Laboratory tests included renal function, serum immunoglobulins, autoantibodies, and immunofixation electrophoresis. Computed tomography (CT) and biopsies of the kidney and cervical lymph node were performed. Histopathologic analysis included light microscopy, immunohistochemistry (IHC), Congo red staining with polarized light, immunofluorescence (IF), and electron microscopy (EM).

Initial tests revealed anemia (HGB 58 g/L), hypoalbuminemia (21.4 g/L), elevated IgG (67.9 g/L), and markedly increased IgG4 (24.6 g/L). No mooclonal immunoglobulin was detected in serum or urine. ANA was positive at a high titer (1:10,000), while ANCA, anti-GBM, and viral markers were negative. CT scans demonstrated splenomegaly and generalized lymphadenopathy.

Light microscopy showed nine glomeruli, eight of which were globally sclerosed, and one exhibited a fibrotic crescent. The interstitium displayed dense inflammatory infiltrates consisting of lymphocytes, eosinophils, and plasma cells, with severe tubular atrophy and storiform fibrosis. IHC demonstrated abundant CD138-positive plasma cells. Notably, IgG4-positive plasma cells accounted for over 60% of the IgG-positive plasma cells in the interstitium. Congo red staining revealed congophilic deposits in the interstitium, showing apple-green birefringence under polarized light. IHC confirmed positivity for AA protein (Figure 1). IF was negative for IgG, IgA, IgM, and both κ and λ light chains in glomeruli and tubulointerstitium, excluding light-chain–related amyloidosis. EM failed to reveal well-formed amyloid fibrils due to limited tissue.

Cervical lymph node biopsy showed preserved architecture with numerous plasma cells infiltrating interfollicular regions and increased high endothelial venules. IHC confirmed VS38c-positive plasma cells without light-chain restriction. The IgG4/IgG plasma cell ratio exceeded 70%, consistent with IgG4-related lymphadenopathy (Figure 2). These findings established a diagnosis of IgG4-RD with renal and lymph node involvement, IgG4-TIN, and concurrent AA amyloidosis.

The patient received oral prednisone (initially 40 mg/day, tapered gradually) and cyclophosphamide (50 mg/day added after 3 months). Serum IgG4 declined from 24.6 g/L to 10.1 g/L, CRP decreased from 97 to 16.1 mg/L, and Scr improved from 273.1 to 120 μmol/L after 10 months (Figure 3). Proteinuria decreased to 1.16 g/24 h, and the patient achieved stable renal function under maintenance therapy.

This case represents the first report of IgG4-TIN coexisting with renal AA amyloidosis. Chronic inflammation from IgG4-RD may drive persistent SAA elevation, leading to secondary AA amyloid deposition. Accurate diagnosis requires histopathological evaluation with Congo red and IgG4/AA immunostaining. Immunosuppressive therapy achieved significant improvement in renal and systemic parameters. IgG4-RD should be recognized as a potential, though rare, cause of secondary AA amyloidosis, underscoring the importance of renal biopsy in patients with unexplained renal dysfunction and elevated IgG4.