title: A case of infection-associated antiproteinase-3-negative cytoplasmic antineutrophil cytoplasmic antibody pauci-immune focal necrotizing glomerulonephritis.
abstract: We present the case of a man with Gram-negative sepsis and exposure to oral silica who developed pauci-immune focal necrotizing glomerulonephritis (PI-FNGN) in the setting of a subacute polymicrobial central venous line (CVL) infection. He developed a cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) that was antiproteinase-3 (PR-3) and antimyeloperoxidase (MPO) antibody negative. We believe this is the first reported case of Gram-negative sepsis-associated PI-FNGN. Chronic silica exposure is a leading environmental risk factor in the development of ANCA vasculitis. Oral silica is a common pharmaceutical additive and its bioavailability is being recognized. Oral silica, therefore, may also be a risk for development of autoreactivity. The PI-FNGN resolved with antibiotic therapy alone. The C-ANCA titer declined as the PI-FNGN resolved. The case supports experimental and observational research that environmental exposures act as adjuvants for an immune response and also provide epigenetic triggers for autoreactivity. The C-ANCA was negative for PR-3, its major antigen. C-ANCA antigen specificity may depend on the pathogenesis of the underlying disease, potentially elicited by a cross-reaction of an antibody to foreign and self target antigen sequence homology or alternatively elicited by antigenic epitope spread.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. ekbell@uab.edu
authors.forename: Emmy K
authors.initials: EK
authors.lastname: Bell
authors.forename: Sumant S
authors.initials: SS
authors.lastname: Chugh
authors.forename: William J
authors.initials: WJ
authors.lastname: Cook
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D005490:Focal Infection / Q000276:immunology* / Q000473:pathology; D005921:Glomerulonephritis / Q000209:etiology* / Q000473:pathology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D010447:Peptide Hydrolases / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D018805:Sepsis / Q000276:immunology / Q000473:pathology; D012822:Silicon Dioxide / Q000009:adverse effects; D014657:Vasculitis / Q000150:complications / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D012822:Silicon Dioxide; D009195:Peroxidase; D010447:Peptide Hydrolases