The study, “Clinical impact of subgrouping ANCA-associated vasculitis according to antibody specificity beyond the clinicopathological classification,” appeared in the journal Rheumatology.
Different AAV subtypes share overlapping features, particularly the subtypes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). However, these two subsets are associated with distinct ANCA antibody types: while GPA patients mainly have cytoplasmic ANCA — directed against the PR3 protein — those with MPA more commonly have perinuclear ANCA antibodies (mainly targeting myeloperoxidase or MPO).
Despite disease subtype, antibody type is also linked to common characteristics: ANCA patients with PR3 antibodies are more frequently male, have more common ear, nose, throat or ocular involvement, and better renal and overall survival than those with anti-MPO antibodies.
Recent studies have attempted to combine clinical and serological classifications, such as renal AAV with or without anti-PR3 ANCA, or renal AAV with or without wide-extent extra-renal disease. Other scientists have focused on the specific features of patients positive for ANCA-MPO compared with those positive for ANCA-PR3.
In the study, a team at Normandie Université, in France, decided to conduct a retrospective analysis of the impact of AAV classifications based on clinical and/or ANCA antibody specificity.
A total of 150 patients (83 men) were identified at Caen University Hospital from January 2000 to June 2016. Ninety-four had GPA and 56 had MPA. As for ANCA antibodies, 87 were positive for ANCA-PR3 antibodies, and 63 had ANCA-MPO antibodies. Median age at diagnosis was 62 years.
The patients experienced mainly constitutional symptoms — which may include weight loss, fever, fatigue, and malaise — and showed renal and pulmonary involvement. Twenty-nine deaths and 93 relapses in 57 patients were observed after a median follow-up of 50.5 months.
Patients in the GPA and anti-PR3 groups showed less frequent renal involvement, but more common ear, nose, throat, and rheumatologic symptoms than the patients in the MPA and anti-MPO groups.
GPA patients also had lung involvement more frequently, were more likely to relapse, and had a higher initial Birmingham Vasculitis Activity Score (BVAS) — an indicator of AAV activity — and shorter relapse-free survival but better renal survival than MPA patients, regardless of ANCA antibody.
Relapse-free and renal survival rates did not differ between anti-PR3 and anti-MPO patients.
Among GPA patients, the only parameter found significantly different between antibody types was higher mortality in people with anti-PR3 antibodies, mostly due to AAV itself (six cases). Among those with MPA, the only difference was more frequent lung involvement in patients with anti-MPO antibodies than in patients with anti-PR3 antibodies.
GPA patients with anti-MPO antibodies were less frequently men. They had more limited forms of AAV, fewer deaths, more relapses, higher initial BVAS scores, more frequent ear, nose, or throat involvement, and shorter relapse-free survival but better overall survival than MPA patients with the same antibodies.
The data further revealed that GPA patients with anti-PR3 antibodies had renal involvement less frequently, had ear, nose or throat, and lung symptoms more often, were more prone to relapse, and had shorter relapse-free survival than MPA patients with this antibody type.
The type of treatment did not differ in any of the comparisons.
Noting that the limited number of patients may explain why no differences in relapse rates were found when comparing ANCA antibodies, the scientists concluded that “to subdivide AAVs seems to be less useful and meaningful than the clinicopathological classification, since the distinction between GPA and MPA better predicts the prognostic patterns of the disease.”
As a result, “the combination of clinicopathological and serological classifications does not appear to bring additional value,” they said.