Alternative Complement Pathway in Anca-Associated Glomerulonephritis as a New Target for Treatment

The Anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitides are characterized by systemic vasculitis in combination with the presence of anti-neutrophil cytoplasmic antibodies [1]. ANCA-associated glomerulonephritis is considered “pauci-immune” with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement in renal biopsies. Because of this relative paucity of complement in vessels, complement system was not initially envisioned as an important participant in the pathogenesis of ANCA vasculitis and ANCA glomerulonephritis [2]. We recently published a paper were we evaluated the prevalence and clinical significance of immune deposits in ANCA-associated glomerulonephritis. The results showed that in a total of 53 patients, typical pauciimmune GN was found in 39 patients (73.5%). In 14 patients (26.4%) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in patients with immune deposits. C3 deposition on the capillary wall was the most frequent finding (64.2%), followed by C3+IgG(21.4%) and IgG alone (14.2%). Normal serum complement C3 and C4 levels were observed in 50 patients (94.33%), only 3 (5.6%) were found to have slightly low levels. We did not find correlation between C3 deposits in renal tissue and levels of C3 in peripheral blood. One possible explanation could be that there is not immune complex deposition, but rather expression of activation of the alternative complement pathway, without real consumption of C3 [3].