Background/Purpose: Knowledge of disease characteristics and long-term outcomes of dual-positive patients (DPP) exhibiting anti-neutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies is limited to small studies in European cohorts. Data regarding disease characteristics, treatment modalities, and disease outcomes from North American populations are limited to case reports.

Methods: We performed a comparative retrospective chart review from a single center of adult DPP with both ANCA and anti-GBM antibodies and Single-positive patients (SPP) with only anti-GBM antibodies presenting between 1/1/2014 – 2/8/2023. The follow-up period ranged from 1- 84 months. 9 DPP and 17 SPP were identified. 14 patients not meeting the clinical criteria for ANCA vasculitis or GBM disease as determined by treating physicians were excluded.

Results: 50% (n=6) of the patients with anti-GBM antibodies also tested positive for ANCA at the time of diagnosis. 5 of these patients had myeloperoxidase (MPO) antibodies, none had anti-proteinase-3 (PR-3) antibodies. The median age was 70 years for DPPand 67 years for SPP. DPP presented with acute renal failure (ARF) (n=5), pulmonary-renal syndrome (n=2), and isolated diffuse alveolar hemorrhage (DAH) (n=1). 6 SPP presented with ARF and 2 with pulmonary-renal syndrome. A similar number of DPP and SPP required dialysis at initial presentation however more SPP had GFR< 15 (n=5) as compared to DPP (n=4). Median serum creatinine was 8.5 mg/dL for SPP and 7.8 mg/dL for DPP. 11/12 patients underwent renal biopsy, 10/12 showed crescentic glomerulonephritis (CGN) and 8/12 had linear IgG staining on immunofluorescence. Pulmonary disease was more severe in DPP with 2 patients requiring stay in the intensive care unit (ICU) and 1 patient requiring mechanical ventilation as compared to 1 SPP requiring ICU stay. DPP pulmonary diagnoses include pulmonary fibrosis (n=2), and pulmonary nodules (n=1), which were not seen in SPP. All 5 DPP requiring dialysis at presentation remained dialysis dependent.1 SPP requiring dialysis at diagnosis was able to stop dialysis after 11 months. All patients received plasmapheresis except for 2 SPP;1 with sepsis and 1 with 100% crescents. All patients received pulse dose steroids. DPP were mostly treated with rituximab (n=5) while most SPP patients received cyclophosphamide (n=4). DPP received maintenance immunosuppression with rituximab (n=2) and mycophenolate mofetil (n=2) for a duration ranging from 3-18 months. Only 1SPPreceived maintenance steroids over 4 years until renal transplant. 1 DPP and 1 SPP who did not receive immunosuppression due to comorbidities died. 5/6 DPP had no relapse in the study period. One patient who developed DAH2 years after initial presentation was successfully treated with steroids and Rituximab.

Conclusion: Half (50%) of this cohort of anti-GBM-positive patients also had positive ANCA serology, highlighting the importance of testing for both antibodies in CGN. DPP presented with mixed clinical features of ANCA vasculitis and anti-GBM disease. Patients with dual positivity may have an increased risk of disease relapse upon discontinuation of immunosuppression.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-characteristics-treatment-patterns-and-clinical-outcomes-in-patients-with-dual-positive-anti-neutrophil-cytoplasmic-antibody-and-anti-glomerular-basement-membrane-antibody-a-single-center/