The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) comprise granulomatosis with polyangiitis (GPA), primarily associated with antibodies to proteinase 3 (PR3-ANCA); microscopic polyangiitis (MPA); and eosinophilic granulomatosis with polyangiitis (EGPA), both principally associated with antibodies to myeloperoxidase (MPO-ANCA).
ANCA directed against proteinase 3 (PR3) are preferentially associated with GPA, and anti-myeloperoxidase (MPO) ANCA are associated mainly with MPA and eosinophilic GPA (formerly known as Churg-Strauss syndrome).
Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome are idiopathic systemic vasculitides in which circulating anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) or myeloperoxidase (MPO) are commonly found.
Wegener's granulomatosis, microscopic polyangiitis and Churg Strauss syndrome are small-vessel vasculitides associated with anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) and myeloperoxidase (MPO).
Antineutrophil cytoplasmic autoantibodies (ANCA) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are closely associated with the idiopathic systemic necrotizing vasculitides, in particular Wegener's granulomatosis, microscopic polyangiitis and its renal limited manifestation, and Churg Strauss Syndrome.
Recently, the first large-scale randomised controlled trial on eosinophilic granulomatosis with polyangiitis proved the efficacy of anti-interleukin-5 mepolizumab.
We also review the evidence to date regarding the efficacy of mepolizumab (an anti-IL-5 monoclonal antibody) in severe eosinophilic asthma and the smaller evidence base regarding its efficacy in EGPA, an indication for which it recently received U.S. Food and Drug Administration approval.
Mepolizumab has been licensed for the management of EGPA and is applied with the aim to abrogate the underlying immunologic process by blocking interleukin-5.
Mepolizumab, an anti-interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis.
Eosinophils number correlated with the percentage of NETs in the whole EGPA group (r=0.53, p=0.039), but we failed to observe the correlation with an eosinophil cationic protein (r=0.49, p=0.058).
The central role of autoimmunity has been confirmed by the significant association with HLA polymorphisms; interestingly, the three main AAV subtypes are associated with distinct HLA variants, i.e. granulomatosis with polyangiitis (Wegener's GPA) with HLA-DP1, microscopic polyangiitis with HLA-DQ and eosinophilic GPA (Churg-Strauss) with HLA-DRB4.
The TCR β-variable (BV) chain repertoire and third complementarity determining region (CDR3) of peripheral CD4+ and CD8+ cells in EGPA patients and age-matched controls and the expression of cytokines and chemokine receptors were investigated.
Significant differences were observed only in serum levels of MDC, IL-8, MIP-1a and -1b, TNF-α, each of which were lower in patients with active EGPA than in healthy controls (p<0.0001).
Peripheral blood eosinophil count or ILC2 count, and serum sST2 or TSLP concentration were higher in patients with EGPA at onset than in those with EGPA at relapse or remission, or in those with BA or CEP.