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Abstract: PO1961

Seronegative Anti-GBM: A Spectrum of Disease

Session Information

Category: Trainee Case Report

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Illescas, Alisa, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Kuperman, Michael Benjamin, Arkana Laboratories, Little Rock, Arkansas, United States
  • Combs, Sara, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Teixeira, J Pedro, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
Introduction

Glomerulonephritis (GN) due to anti-GBM disease is usually associated with detectable antibodies against the NC1 domain of the type IV collagen alpha-3 chain [NC1-α3(IV)], but a subset of seronegative atypical disease has been described with no lung involvement, non-crescentic GN on biopsy, and indolent course. We present a case of anti-GBM disease that is neither typical nor atypical.

Case Description

A 56-year-old woman with hypertension and obesity underwent renal biopsy after routine labs showed rise in creatinine (Cr) above baseline of 1.5 mg/dL 6 months prior and hemoproteinuria on UA. The results [Figure] prompted transfer to our center. On admit, she noted mild chronic dyspnea but denied cough or hemoptysis. She had mild hypertension (146/80) and trace edema. Cr had risen to 4.5, urine protein was 3.4 g/g Cr, and chest x-ray was clear. She was started on IV corticosteroids and plasma exchange (PLEX). Anti-GBM IgG [multiplex bead assay, ARUP], drawn prior to PLEX, was negative (4 AU/mL, upper limit normal 19). She was treated with IV cyclophosphamide and 7 PLEX sessions over 2 weeks and her Cr stabilized at 3.5. She avoided dialysis and was discharged on prednisone with plans to continue monthly cyclophosphamide.

Discussion

Our patient exhibited an intermediate phenotype of anti-GBM disease with crescentic GN, subacute Cr rise, no lung involvement, and negative serology. Modern assays for anti-GBM antibody have a sensitivity of 94-100%. However, negative serology is also seen in rare cases of anti-GBM GN due to antibodies against epitopes of the GBM other than NC1-α3(IV). Our case illustrates that a negative anti-GBM antibody does not exclude anti-GBM disease which is ultimately a pathologic diagnosis. It also suggests a spectrum exists between classic and atypical anti-GBM disease, but favorable outcome is possible regardless with biopsy-directed therapy.

Biopsy yielded 35 glomeruli, 15 globally sclerotic and 12 with fibrinoid necrosis, cellular crescents (panel A, PAS, 600x), or fibrocellular crescents. RBC casts and 50% interstitial fibrosis were seen. IF showed linear GBM staining with λ (3+), IgG1 (3+), and IgG4 (3+, panel B, 400x).