Abstract: PUB575
ANCA-Associated Glomerulonephritis with Linear GBM Staining in the Absence of Anti-GBM Antibody: A Variant of Double-Positive MPO and Anti-GBM Antibody
Session Information
Category: Trainee Case Report
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Cho, Janis, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
- Kanwar, Yashpal S., Northwestern University Medical School, Chicago, Illinois, United States
- Aggarwal, Vikram, Northwestern University - Feinberg School of Medicine, Chicago, Illinois, United States
Introduction
Anti-glomerular basement membrane antibody disease (Anti-GBM) is a rare disease with severe renal-pulmonary manifestation. About 10-38% of patients with anti-GBM nephritis also has positive ANCA at the time of diagnosis, most often P-ANCA. They are termed double positive and has different prognosis and outcomes. Recently, there has been described patients with renal biopsies with linear GBM immunoglobulin staining without detectable anti-GBM antibodies. Such diagnosis is termed atypical anti-GBM disease. We present a case with features of both atypical anti-GBM disease overlap with ANCA-associated vasculitis (AAV).
Case Description
A 70 year old Indonesian male with past medical history of vitiligo, chronic kidney disease, hypertension, and prostate cancer with recent radiation treatment was hospitalized for management of overt hematuria and acute kidney injury. He had nephritic presentation and no evidence of obstructive nephropathy. Kidney biopsy showed 40% crescentic glomeruli, necrotizing glomerular lesions, 20% sclerosis and tubular atrophy, few small subendothelial deposits on electron microscopy, and linear GBM reactivity with anti-IgG on immunofluorescence. Serology showed negative Anti-GBM antibody, positive P-ANCA antibody 1:160 and MPO antibody elevated to 21.4. He had no pulmonary manifestations. He received high dose steroid, 6 doses of plasmapheresis and rituximab. He was discharged with tapering steroids and received repeat rituximab in 2 weeks. At 3 month, creatinine improved to nadir 2.08 mg/dl and started azathioprine for maintenance therapy.
Discussion
Our patient had linear IgG staining consistent with Anti-GBM disease without anti-GBM antibody (Atypical anti-GBM disease) overlap with P-ANCA positivity. While overlap of typical anti-GBM disease and AAV has been described, co-existence of atypical anti-GBM nephritis and AAV as a variant is rarely reported. The overlap syndromes with double positive antibodies (anti-MPO and anti-GBM) has a distinct clinical phenotype needing better understanding of pathogenesis, recognition of specific epitope, classification, prognostication and different treatment strategies. Recently, anti-peroxidasin antibodies disrupting collagen structure of GBM and cross-reacting with MPO have been identified and can help elucidate such overlap syndromes.