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.

Fig. 1

(A) Glomerulus with small segmental necrotizing lesion. Note the absence of mesangial or endocapillary proliferation in the rest of the glomerulus. (H&E; original magnification ×200). 173 × 130 mm (300 × 300 DPI) (B) Glomerulus with large cellular crescent. (Periodic Acid Schiff-Hematoxylin stain; original magnification ×200). 173 × 130 mm (300 × 300 Dots per inch)