Abstract: TH-PO179

A Case of RPGN with Dual Positive Anti-GBM and PR3-ANCA Antibodies

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Chowdhury, Nawsheen, Winthrop university hospital, Mineola, New York, United States
  • Shirazian, Shayan, Winthrop University Hospital , Mineola, New York, United States
  • Miyawaki, Nobuyuki (Bill), Winthrop University Hospital , Mineola, New York, United States
  • Drakakis, James, Winthrop University Hospital , Mineola, New York, United States
Background

Anti-GBM disease and ANCA associated vasculitis are the major differentials for patients presenting with RPGN and pulmonary involvement. We report a case of unusual double positivity of both anti-GBM and PR3-ANCA antibodies, as most of the patients with both ANCA and anti-GBM antibodies are MPO-ANCA positive.

Methods

A 47-year-old female presented to the hospital with fatigue, malaise, and hemoptysis. Imaging of the chest revealed patchy consolidations and cavitary lesions. Initial creatinine was 1.1 mg/dL, but during the hospital course she developed rapidly progressive renal failure (peak creatinine of 2.6 mg/dL) in the setting of proteinuria and microscopic hematuria. An anti-GBM antibody titer was 135 units/mL and anti-proteinase 3 (PR3) antibody titers were > 100 units. Anti-myeloperoxidase (MPO) antibody titers were negative. Therapy was initiated with pulse steroids and plasmapharesis. Renal biopsy (done after having already received significant immunosuppression) revealed a focal crescentic glomerulonephritis with cellular crescents involving 29% of glomeruli. The patient received a dose of IV Cyclophosphamide and continued on tapering doses of prednisone. She was discharged with a creatinine of 1.5 mg/dL and negative PR3-ANCA and anti-GBM antibody titers. She completed 4 months of oral Cyclophosphamide and currently has a creatinine of 0.7 mg/dL on Azathioprine.

Conclusion

About 30% of patients with anti-GBM disease will have concurrent ANCA seropositivity, most of which are MPO-ANCA associated (74%). Our patient belonged to a smaller subset of patients with anti-GBM and PR3-ANCA antibodies. The reason for the emergence of dual antibody production is not known, however there have been some pathophysiological hypotheses for how MPO-ANCA may injure the glomerular basement membrane, expose antigens and lead to the development of an anti-GBM antibody. Most of the literature on patient and renal survival in dual positivity involves anti-GBM and MPO-ANCA antibodies. It is not clear that these descriptions of mechanism and outcome also apply to an overlap with PR-3-ANCA and more literature is required to help elucidate the potential clinical implications.