Abstract
The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener’s Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control.
Highlights
The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype
Several genetic loci were significantly associated with associated vasculitidies (AAV), on subgroup analysis different associations were identified with GPA and microscopic polyangiitis (MPA) [50]
It is clear that there are different genetic contributions to AAV associated with proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibodies (ANCA) to that associated with MPO-ANCA, and further studies are planned to address the genetics of these two conditions separately which may identify further disease specific genetic susceptibility loci
Summary
The incidence of AAV across different populations is broadly similar at 12–18 per million population per year [23, 24]. The prevalence of GPA in a predominantly Northern European Caucasian population from New Zealand was similar to that in the UK and Norway [26] These population differences in predominant type of AAV may reflect genetic differences or environmental factors. A number of candidate gene association studies have been published implicating a number of genetic variants, both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) in AAV risk. Many of these were small and unreplicated [47,48,49]. Several genetic loci were significantly associated with AAV, on subgroup analysis different associations were identified with GPA and MPA [50]
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