IgA Nephropathy With c-ANCA Positivity in a Patient With Crohn Disease

ABSTRACT

Introduction: IgA nephropathy (IgAN) is an immune complex glomerulonephritis (GN) characterized by glomerular deposition of IgA-dominant immune complexes, often accompanied by mesangial hypercellularity. Antineutrophil cytoplasmic antibodies (ANCAs) cause small-vessel vasculitis and pauci-immune crescentic GN. The coexistence of ANCAs and IgAN is quite rare. ANCAs have been associated with inflammatory bowel disease (IBD) but are more prevalent in ulcerative colitis (~75%) than Crohn's disease (~17%). IBD-associated ANCAs are usually p-ANCA or atypical ANCA rather than c-ANCA. ANCA-associated vasculitis (AAV) can be associated with tumor necrosis factor-alpha inhibitors such as infliximab. We report a rare case of c-ANCA PR3-positive IgAN in a patient with IBD treated with infliximab who presented with proteinuria. Case Description A 27-year-old female with history of Crohn's disease since 2010 treated with infliximab, allergic rhinoconjunctivitis, mild asthma, erythema nodosum in June 2021 (resolved with prednisone), Charcot-Marie-Tooth disease, psoriasis, and COVID-19 disease in Oct 2021, was found to have positive c-ANCA (1160) and PR3 (5.0 AI, reference <1.0) in Dec 2021, raising question of vasculitis. Her rhinosinusitis was well controlled with allergy medications without oral steroids. She was referred to Nephrology for proteinuria with urinalysis (UA) in April 2022 showing 2+ protein, 3+ blood, 2-10 WBC, 20-50 RBC. Urine protein/creatinine ratio was 1.9. She had foamy urine but no gross hematuria. She previously had UA with packed RBC in June 2021. Urogram showed non-specific bladder wall thickening. Cystourethroscopy was negative. In April 2022, her BP was 97/66 and she had no edema. A renal biopsy in May 2022 revealed IgAN (M0 E1 S1 T0 C0). She was started on lisinopril and fish oil. Discussion(s) This is a very rare case of c-ANCA PR3-positive IgAN in IBD treated with infliximab. The patient's history of sinusitis along with c-ANCA PR3 antibody positivity suggested possibly an AAV associated with infliximab, which has been reported rarely in IBD. Her proteinuria of 1.9 g/day raised concern for GN due to pauci-immune AAV. However, renal biopsy showed IgAN rather than AAV. This case highlights the importance of renal biopsy in establishing a definitive diagnosis of glomerular disorders in patients with ANCA positivity, as serum ANCAs do not necessarily represent pauciimmune GN.