Relapses in Wegener's granulomatosis: the role of infection.

Abstract

Summary and conclusionsOut of 20 relapses that occurred in patients with Wegener's granulomatosis, nine were provoked by bacterial or viral infection. Seven of these occurred during maintenance treatment in response to infection with common pathogens, and treatment of the infection alone was insufficient to produce remission. Circulating immune complexes were seen only in relapses due to infection and rarely in infections that occurred without relapse. A possible mechanism for infection-provoked relapses is that infection-derived complexes reactivate disease; alternatively, the acute-phase or cellular response to infection may enhance quiescent disease.Infection may exacerbate Wegener's granulomatosis and other autoallergic diseases, but whether it does so by a common mechanism is not known and further study is required. Introduction A study of patients being treated for antiglomerular basementmembrane disease identified intercurrent infection as an important cause of relapse and led to the recognition of infectioninduced enhancement of antibody-mediated injury.' Although its cause is still not clear, several mechanisms have been considered, including activation of inflammatory cells in response to infection, increased concentrations of acute-phase proteins such as fibrinogen and C-reactive protein, and the superimposition of infection-derived immune complexes. We report here on part of a prospective analysis of the effect of infection in autoallergic diseases, which investigated the importance of infection in relapses of Wegener's granulomatosis, a condition of uncertain aetiology but probably having an allergic pathogenesis of immune complex type. Enhanced tissue injury after infection has also been noted in other immunologically mediated diseases,2-8 and the possibility arises that exacerbation of allergic tissue damage by infection might be a more general phenomenon. Patients and methodsWe studied 18 patients with Wegener's granulomatosis. Three died early in the course of their disease, and the remainder were followed up for periods ranging from three months to three years; eight are still alive. Treatment was generally started with a regimen including cyclophosphamide, azathioprine, and prednisolone and in some cases plasma exchange (referred to later as the "induction

Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

“…Cardiovascular involvement has been identified as a predictor of a relapse [35]. In a small study, infection has been reported to be a risk factor for GPA [39]. In a larger study, however, we could not confirm this [38].…”

Toll‐like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll‐like receptor 9 drives Th1 autoimmunity in murine vasculitis

“…In addition to the seasonal association with disease (14), infection may predate the initiation of AAV and can induce disease relapses (35,36). This is particularly true of MPO-associated disease; in one study, 11 of 18 patients with severe crescentic glomerulonephritis had a preceding respiratory tract infection (37).…”

Dendritic cell uptake of human apoptotic and necrotic neutrophils inhibits CD40, CD80, and CD86 expression and reduces allogeneic T cell responses: Relevance to systemic vasculitis

“…The production of TNF␣, IL-1, and IL-8 by macrophages is significantly up-regulated when they are incubated with ANCA-opsonized apoptotic neutrophils compared with normal IgG-opsonized or nonopsonized apoptotic neutrophils (34,53). TNF␣ levels prior to development of vasculitis have not been studied, but, since many patients have a history of chronic infection before the onset of vasculitis (54) and intercurrent infection often precedes relapse (55), it is likely that synthesis of TNF␣ is increased. If this is the case, it is conceivable that uptake of apoptotic neutrophils by DCs within an environment rich in TNF␣ might encourage development of an autoimmune response toward neutrophil PR3 or MPO.…”