A case report of atypical anti-glomerular basement membrane disease

Abstract

Background: Anti-glomerular basement membrane (anti-GBM) disease is characterized by crescentic necrotizing glomerulonephritis, with linear deposits of immunoglobulin G (IgG) in the GBM. Classic anti-GBM disease is clinically associated with rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Some patients have a better renal prognosis and milder symptoms than those with classic anti-GBM disease, which is termed atypical anti-GBM disease.

Case presentation: A 43-year-old Japanese woman was admitted to our hospital complaining of hematuria that had persisted for more than one month. Serological examination revealed negativity for anti-nuclear, anti-neutrophilic cytoplasmic, and anti-GBM antibodies. However, renal biopsy showed cellular crescents. Immunofluorescence revealed strong diffuse linear capillary loop staining for IgG. An indirect immunofluorescence antibody method was performed by applying the patient serum to normal kidney tissue to confirm the presence of autoantibodies binding to the GBM. Using this method, anti-GBM antibodies were detected. The patient was treated with high-dose steroids, cyclophosphamide, and plasma exchange. Aggressive treatment resolved proteinuria and hematuria and improved renal function.

Conclusions: Renal biopsy is crucial in the diagnosis of anti-GBM disease, especially when serological tests are negative. Accurately identifying the presence of anti-GBM disease is important to initiate optimal treatment.

Keywords: Atypical anti-GBM disease; Indirect immunofluorescence antibody method; Linear deposits of IgG.

Fig. 1

Diagnostic studies. a Periodic acid-Schiff (PAS) staining at a low magnification (×200). Crescentic glomerular lesions of b PAS, c Periodic acid-methenamine-silver, and d Masson’s trichrome staining (× 400). Scale bar: 100 μm (a) and 50 μm (b-d). e Electron microscopy image. Scale bar: 2 μm. f Immunofluorescence studies using frozen sections. Linear capillary loop staining for IgG, and C3 (1+) was positive on glomerular capillaries. g IgG1 and IgG4 were positive. Staining for IgG1 (3+) was dominant, and the staining intensity for IgG4 (1+) was rather weak. Staining for IgG2 and IgG3 was negative. Immunofluorescence staining was positive for both kappa and lambda. h Immunofluorescence studies using FITC-labeled anti-human IgG (F2020; Dako, Glostrup, Denmark) to determine the presence of IgG binding to the GBM by applying the patient serum to frozen normal kidney tissue after pretreatment in 10 M urea solution for 10 minutes. Anti-GBM antibodies were detected in the Serum (+) specimens in which patient serum was reacted in normal kidney tissue. In contrast, no IgG findings was detected in Serum (−) specimens in which patient serum was excluded in same immunostaining procedures

Fig. 2

Patient’s clinical course. Changes in serum creatinine (Cr, red lines) and urine protein-to-creatinine ratio (UPCR, green lines). mPSL: methylprednisolone, PSL: prednisolone, CY: cyclophosphamide, PE: plasma exchange