ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES, AUTOANTIGENS, AND SYSTEMICVASCULITIS

Antineutrophil cytoplasmic antibodies (ANCA) encompass a heterogeneous group of autoantibodies targeting antigens in neutrophils (PMN), mono cytes, and endothelial cells. ANCA are routinely detected by the indir ect immunofluorescence technique (IFT) and at least three different pa tterns of fluorescence can be distinguished which have been assigned t he acronyms cANCA, pANCA and aANCA. cANCA is mostly induced by protein ase 3 (PR3) antibodies (PR3-ANCA), and pANCA by myeloperoxidase (MPO) antibodies (MPO-ANCA), while aANCA has unidentified subspecificity. Ov er the past decade, ANCA have been the subject of extensive investigat ion. They have proved to be of significant value both as diagnostic to ols and for follow-up in several forms of systemic vasculitis (e.g. We gener's granulomatosis, WG; microscopic polyarteritis, MPA; Churg-Stra uss syndrome, CSS) which are now termed; 'ANCA-associated vasculitides '. Furthermore, it is suspected that the presence of ANCA is an import ant factor in the pathogenesis of these disease groups. Data regarding the detection of ANCA and their diagnostic value and role in the path ogenesis of vasculitic disorders will be discussed in this review. Gro wing evidence points to a pathophysiological and diagnostic relevance of the distribution of the ANCA target antigens PR3 and MPO (presence in the circulation, on cellmembranes, and in tissue extracellularly). An autoimmune process has been implicated in the pathogenesis of ANCA- associated vasculitis, but it is uncertain which mechanism underlies t he induction of the ANCA-related immunoresponse. In this paper mechani sms such as antigenic cross-reactivity between human PMN proteins and extrinsic antigens by molecular mimicry, idiotypic immunoglobulin regu lation, and T-cell reactivity to PR3 and MPO will be discussed.