Abstract
The proteinase 3 (PR3)-positive anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) granulomatosis with polyangiitis (GPA) has been associated with chronic nasal S. aureus carriage, which is a risk factor for disease relapse. The present study was aimed at comparing the genetic make-up of S. aureus isolates from PR3-ANCA-positive GPA patients with that of isolates from patients suffering from myeloperoxidase (MPO)-ANCA-positive AAV, and isolates from healthy controls. Based on a DNA microarray-based approach, we show that not only PR3-ANCA-positive GPA patients, but also MPO-ANCA-positive AAV patients mainly carried S. aureus types that are prevalent in the general population. Nonetheless, our data suggests that MPO-ANCA-associated S. aureus isolates may be distinct from healthy control- and PR3-ANCA-associated isolates. Furthermore, several genetic loci of S. aureus are associated with either PR3-ANCA- or MPO-ANCA-positive AAV, indicating a possible role for pore-forming toxins, such as leukocidins, in PR3-ANCA-positive GPA. Contrary to previous studies, no association between AAV and superantigens was detected. Our findings also show that a lowered humoral immune response to S. aureus is common for PR3-ANCA- and MPO-ANCA-positive AAV. Altogether, our observations imply that the presence or absence of particular virulence genes of S. aureus isolates from AAV patients contributes to disease progression and/or relapse.
Highlights
The systemic autoimmune diseases granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) belong to the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAVs)[1]
The present study provides a first comprehensive portrait of the gene repertoire of S. aureus isolates from patients suffering from the proteinase 3 (PR3)-ANCA- and MPO-ANCA-associated forms of the autoimmune disease AAV
Our retrospective study has some limitations, the results show that the PR3-ANCA-AAV patients, and the MPO-ANCA-AAV patients mainly carry S. aureus types that are carried in the general population
Summary
The systemic autoimmune diseases granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) belong to the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAVs)[1]. AAVs are multifactorial diseases with numerous contributing genetic and environmental factors[3,4] Among the latter, microbial upper airway infections have been associated with PR3-ANCA-GPA. We have previously demonstrated that PR3-ANCA-GPA patients carry highly diverse S. aureus types that mirror the general S. aureus population[11]. This finding does not rule out the possibility that S. aureus carried by PR3-ANCA-positive patients possesses a particular genetic make-up that could contribute to disease progression and/or relapse. The present study was aimed at investigating the gene repertoire of S. aureus nasal isolates from PR3-ANCA-positive patients and to compare it to that of S. aureus isolates from MPO-ANCA-positive patients and from healthy controls (HC). The humoral immune response of these two AAV patient groups against a comprehensive set of S. aureus antigens was compared, because our previous studies had shown that GPA patient sera contained lower anti-staphylococcal IgG levels than sera from HC11
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