Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis

Abstract

In patients with GN or vasculitis, ANCAs are directed against proteinase 3 (PR3) or myeloperoxidase (MPO). The differences between PR3-ANCA-associated vasculitis (AAV) and MPO-AAV described in the past have been supplemented during the last decade. In this review, we discuss the differences between these two small-vessel vasculitides, focusing especially on possible etiologic and pathophysiologic differences. PR3-AAV is more common in northern parts of the world, whereas MPO-AAV is more common in southern regions of Europe, Asia, and the Pacific, with the exception of New Zealand and Australia. A genetic contribution has been extensively studied, and there is a high prevalence of the HLA-DPB1*04:01 allele in patients with PR3-AAV as opposed to patients with MPO-AAV and/or healthy controls. Histologically, MPO-AAV and PR3-AAV are similar but show qualitative differences when analyzed carefully. Clinically, both serotypes are difficult to distinguish, but quantitative differences are present. More organs are affected in PR3-AAV, whereas renal limited vasculitis occurs more often in patients with MPO-AAV. For future clinical trials, we advocate classifying patients by ANCA serotype as opposed to the traditional disease type classification.

Keywords: ANCA; glomerulonephritis; vasculitis.

Figure 1.

Light microscopy picture of a renal biopsy from a patient with ANCA vasculitis. Around the almost obliterated glomerulus an active granulomatous inflammation can be seen (hematoxylin and eosin staining; original magnification ×40).

Figure 2.

Pathogenic model highlighting the differences between PR3-ANCA and MPO-ANCA vasculitis. PR3-AAV is more common in the northern parts of the world whereas MPO-AAV is more common in the southern parts. Different genetic backgrounds have been found and different etiologic factors are considered. Clinically and histologically both vasculitides differ. On the cellular level, PR3 and MPO exert different effects on endothelial cells. These differences possibly point out separate pathogenic pathways.

Figure 3.

Flow diagram for treatment in AAV. Evidence for every step is given as follows, linked to the symbols in the diagram. (A) Silva et al. and Stassen et al. (B) NORAM trial; (C) MEPEX trial; (D) PEXIVAS trial (table 2); (E ) RAVE trial and RITUXVAS trial; (F) LoVAS trial and RAVELOS study (table 2); (G) CYCLOPS trial; (V) WEGENT trial; (W) CYCAZAREM trial; (X) IMPROVE trial; (Y) MAINRITSAN (table 1), RITAZAREM and SCOUT trials (table 2); (Z) TAPIR trial (table 2).