ANCA Serology

In patients with smaU-vessel vasculitis, the two major autoantigen specificities for ANCAs are for MPO-ANCA (26) and PR3-ANCA (27- 30). MPO and PR3 are enzymes in the primary granules of neutrophils and the lysosomes of monocytes. As discussed in detail later, ANCAs can interact with MPO or PR3 and cause activation of neutrophils and monocytes, which appears to be a primary event in the pathogenesis of vasculitis in patients with ANCAs (30). 

Note that Wegener s granulomatosis limited to the upper respiratory tract has a lower frequency of ANCA (approximately 70%) compared to systemic disease, and Churg-Strauss syndrome with systemic vasculitis and glomerulonephritis has a higher frequency of ANCA than Churg-Strauss syndrome without glomerulonephritis. Abbreviations. ANCA, antineutrophil cytoplasmic autoantibodies MPO, myeloperoxidase PR3, proteinase 3. 

In vitro studies have documented that activation of leukocytes by ANCAs can release factors that are injurious to endothelial cells (52-59). Endothelial injury by ANCA-activated leukocytes requires interplay between multiple cytokine and adhesion molecule ligands and their receptors in the microenvironment at the site of vasculitis (55-59). Overall, in vitro activation of neutrophils by ANCA IgG causes neutrophil adherence to endothelial cells, diapedesis through endothelial monolayers, and release of toxic factors that kill endothelial cells (Fig. 1). Similar events in vivo would result in histologic changes that are characteristic of early acute ANCA-associated vasculitis, including neutrophil margination and infiltration and vascular necrosis. 

Experimental Animal Observations Supporting Pathogenicity of ANCAs 

U Cytokine receptor U Fc receptor W Adhesion moiecule u Adhesion moiecule receptor 

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Vilela RJ, Langford C, McCullagh L, Kass ES. Cocaine-induced oronasal fistulas with external nasal erosion but without palate involvement. Ear Nose Throat J 2002 81(8) 562-3. Rowshani A, Schot LJ, ten Berge JM. C-ANCA as a serological pitfall. Lancet 2004 363 782. 

ANCA-3. Hauer HA, Bajema IM, van Houwelingen HC, Ferrario F, Noel LH, Waldherr R, Jayne DR, Rasmussen N, Bruijn JA, Hagen BC renal histology in ANCA-associated vasculitis differences between diagnostic and serologic subgroups. Kidney Int 2002 61 80-90. 

Two patients developed a cocaine-associated ANCA-positive vasculitis, with retiform purpura, which was typically PR3-positive (c-ANCA>p-ANCA) and most closely resembled Wegener granulomatosis [IS ]. The uniqueness of retiform purpura in the setting of cocaine use suggested levamisole as a possible culprit. In two cases of cutaneous necrosis associated with cocaine use levamisole contamination was suspected [16" ]. Complete clinical resolution of skin lesions usually occurs 2-3 weeks after stopping levamisole and abnormal serology normalizes within 2-14 months. 

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