IngentaConnect Antibodies to selected minor target antigens in patients with ant...

Abstract:

Summary

In patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, indirect immunofluorescence (IF) distinguishes between cytoplasmic (C-ANCA) and perinuclear (P-ANCA) neutrophil staining patterns. In patients with primary systemic vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome, these IF staining patterns correspond broadly with antibodies to the two major antigens: the C-ANCA pattern is associated generally with antibodies to serine protease 3 (PR3) and the P-ANCA pattern with antibodies to myeloperoxidase (MPO). However, some sera positive for ANCA by IF are negative for anti-PR3 and anti-MPO antibodies, suggesting the presence of antibodies to minor antigens of PMN granules. We tested sera from a previously well-defined clinical cohort of patients for antibodies to four possible minor antigens: bactericidal permeability increasing protein, elastase, cathepsin G and lactoferrin. IF-positive (+) sera had significantly higher antibody frequencies to the minor antigens than did the IF-negative (-) sera (P < 0·01). Patients with IF⁺ PR3^-MPO^- sera showed the most varied reactivity to the minor antigens. Among the IF⁺ groups, the IF⁺ PR3⁺/MPO^- sera showed the lowest reactivity to the minor antigens. Patients with well-defined ANCA specificities, e.g. the PR3-ANCA response associated with Wegener's granulomatosis, are less likely than are other patient subsets to have antibodies to minor antigen targets. Autoantibodies to these minor antigens contribute to the overall pattern of ANCA identified by IF and help to explain why the correlation between IF and enzyme immunoassays show discrepancies. While the pathophysiological significance of antibodies to minor target antigens needs further evaluation, they may be markers of inflammation associated with disease processes.

Keywords: ANCA; bactericidal permeability increasing protein; cathepsin G; elastase; lactoferrin; myeloperoxidase; serine protease 3

Document Type: Research article

DOI: 10.1111/j.1365-2249.2007.03453.x

Affiliations: 1: Departments of Pathology, 2: Medicine,

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Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)