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Pauci‐immune glomerulonephritis: the ANCA ‐negative side of the coin
Author(s) -
Ramirez Giuseppe A.,
Mason Justin C.,
Tombetti Enrico
Publication year - 2016
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.12836
Subject(s) - microscopic polyangiitis , medicine , granulomatosis with polyangiitis , proteinase 3 , immunology , rituximab , autoantibody , vasculitis , eosinophilic , anti neutrophil cytoplasmic antibody , glomerulonephritis , clinical significance , antibody , disease , pathology , kidney
Anti-neutrophil cytoplasmic antibodies (ANCAs) were first described as ‘tools for diagnosis and markers of disease activity’ in a set of small vessel vasculitides characterized by frequent renal injury. Since then, a first generation of seminal studies further enforced the clinical and pathogenic relevance of ANCA for granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA) and renal-limited pauci-immune vasculitis, which were thus grouped as ‘ANCAassociated vasculitides (AAVs)’. At the same time, diagnostic advances occurred with the introduction of more accurate quantitative methods (such as enzymelinked or chemiluminescence assays) for the specific recognition of anti-myeloperoxidase (MPO) and antiproteinase-3 (PR3) antibodies, besides conventional immunofluorescence. Recent genetic studies pointed out that AAV subsets can be distinguished not only by clinical diagnosis and organ involvement, but also by ANCA status (i.e. a specific ANCA type was associated with a different genetic background), paving the way to a novel serological classification of AAV. Several additional studies confirm the usefulness of this ANCAcentred approach at a clinical level and support the contention that some pathogenic mechanisms may vary depending on presence and type of ANCAs. For example, ANCA-positive patients with EGPA have more prominent vasculitic manifestations. In addition, antiPR3-positive patients respond better to rituximab (RTX) than to cyclophosphamide, but have a higher cardiovascular risk and are more likely to experience relapse after renal transplant when compared to MPO-positive patients. Finally, the ANCA titre could predict disease flares and indicate the optimal timing for RTX administration (NCT01731561, MAINRITSAN-2 trial). However, while a classification based upon an antiMPO versus anti-PR3 dichotomy seems promising for an accurate clinical-pathogenic stratification of patients, the smaller, but clinically significant subset of ANCA-negative patients remains in an indefinite