Abstract: FR-PO0786
Anti-GBM Disease After Methotrexate Withdrawal in a Patient with Rheumatoid Arthritis in Remission: A Two-Hit Immune Reconstitution Phenomenon
Session Information
- Glomerular Diseases: ANCA Vasculitis, Anti-GBM Disease, and Crescentic GN
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Achakornlak, Thananya, Faculty of Medicine Vajira Hospital, Bangkok, Thailand
- Ngamvichchukorn, Tanun, Faculty of Medicine Vajira Hospital, Bangkok, Thailand
Introduction
Anti-glomerular basement membrane (anti-GBM) disease is a rare, life-threatening autoimmune vasculitis caused by autoantibodies targeting the α3 chain of type IV collagen. Although rheumatoid arthritis (RA) is a common systemic autoimmune disease, its co-occurrence with anti-GBM disease is exceedingly rare. We report a case of anti-GBM disease developing after methotrexate (MTX) discontinuation in a patient with RA in sustained remission, proposing a potential two-hit immune reconstitution mechanism.
Case Description
A 74-year-old female with a three-year history of seronegative RA presented with rapidly progressive glomerulonephritis (RPGN) characterized by acute kidney injury and active urinary sediment. Her RA had been in sustained clinical remission, and methotrexate had been discontinued four months prior to presentation. During the two weeks preceding presentation, she reported a cat scratch. Laboratory investigations revealed high-titer anti-GBM antibodies (1:160), a rapidly declining estimated glomerular filtration rate, dysmorphic red blood cells on urine microscopy, and nephrotic-range proteinuria. Kidney biopsy demonstrated cellular crescentic glomerulonephritis with pathognomonic linear IgG deposition along the glomerular basement membrane. Despite intensive treatment with pulse methylprednisolone, plasmapheresis, and cyclophosphamide, the patient remained dialysis-dependent.
Discussion
We propose a two-hit mechanism: (Hit 1) methotrexate withdrawal leading to immune reconstitution, with loss of peripheral tolerance through dysregulated T-cell control and expansion of autoreactive B-cell clones primed to produce anti-GBM antibodies; (Hit 2) a cat scratch serving as a putative environmental antigenic trigger, precipitating overt anti-GBM antibody production — though this association remains speculative. Clinicians should maintain a high index of suspicion for RPGN following immunosuppressive withdrawal in patients with RA and consider early renal function monitoring and urinalysis after therapy discontinuation. This case raises awareness of a potential rebound autoimmune
A : IgG 3+, Linear pattern
B C : Cellular crescent with fibrinoid necrosis, Silver and PAS 400x,