Background Although their pathophysiology are still largely unknown, there are growing evidences that complement (C) alternative pathway activation is implicated in antineutrophilic cytoplasmic antibody-associated vasculitis (AAV) pathogenesis.
Objectives The aim of our study was to evaluate the clinical characteristics and outcome of AAV patients, according to their serum C levels at diagnosis.
Methods A retrospective monocentric study carried out in Caen University Hospital led to identify proteinase-3 (PR3) or myeloperoxidase (MPO)-ANCA AAV patients (via an ELISA technique). All patients with available C3 and C4 levels (by nephelemetry) at diagnosis were included, except for eosinophilic granulomatosis with polyangiitis (EGPA), which has a different pathophysiology. AAV were classified between granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), and limited or severe forms according to respectively European Medicines Agency vasculitis algorithm and WGET group. Patients were categorized in the hypocomplementemia group if the C3 or C4 level at diagnosis was below the lower limit of the normal range (respectively 750–1400 mg/l and 100–340 mg/l). Categorical variables were reported as percentages and compared using Fisher's tests. Continuous variables were expressed as means and analyzed using Student's t-test. Associations between survival, renal survival and relapse-free survival, and low serum C levels were evaluated by the log-rank test. A p-value <0.05 was considered to be statistically significant.
Results Among the 157 AAV patients identified, 81 were excluded (8 EGPA, 73 without C3 and C4 determinations before treatment initiation). On the 76 AAV included (43 GPA, 33 MPA), median age at diagnosis was 65 years (M/F, 38/38). Clinical presentations included constitutional symptoms (56, 73.7%), pulmonary (52, 68.4%), renal (50, 65.8%), rheumatologic (43, 56.6%), and ear, nose or throat (37, 48.7%) involvements, without statistical differences between groups. Twelve (15.8%) deaths and 41 relapses in 25 (32.9%) patients were noted (median follow-up: 38 months). Four patients (5.3%) had hypocomplementemia: 1 patient had isolated low C3 level, 1 had isolated low C4 level, and 2 had both low C levels. All 4 patients had renal involvement. The C level, controlled in 1 patient, became normal 1 month later. No thrombotic microangiopathy (TMA) features were found on the 2 performed kidney biopsies.
Survival and renal survival were significantly lower in the hypocomplementemia group (p=0.0011 and p<0.001, respectively), but relapse-free survival was similar (p=0.1).
Conclusions Hypocomplementemia at AAV diagnosis may be responsible for worse survival and renal prognosis. This particular phenotype may confer resistance to common immunosuppressive approaches as in thrombotic microangiopathy caused by abnormalities in the regulation of the C system. These results also argue for larger studies and for investigating C pathway targeting.
Disclosure of Interest None declared