Urinary markers of the alternative and lectin complement pathway are increased in IgA vasculitis nephritis

Background. IgA vasculitis (IgAV) is the most common form of childhood vasculitis. Nephritis (IgAVN) occurs in 50% of patients and 1-2% progress to chronic kidney disease stage 5. The pathophysiology of nephritis remains largely unknown, but recent evidence suggests that the complement system may be involved. The aim of this cross-sectional study was to explore whether there is evidence of alternative and/or lectin complement pathway activation in children with IgAVN.Methods. Children with IgAV were recruited and grouped according to proteinuria: IgAVN or IgAV without nephritis (IgAVwoN). Age and sex-matched healthy controls (HCs) were also recruited. Cross-sectional urine and plasma concentrations of complement factor D (CFD), factor B (CFB), and MBL-associated protease 1 (MASP-1) were performed using commercially available enzyme-linked immunoassays.Results. A total of 50 children were included (IgAVN, n = 15; IgAVN, n = 20, HCs, n = 15). The mean age was 8.5 +/- 3.7 years old, male:female ratio was 1:1. Urinary CFD and CFB concentrations were statistically significantly increased in children with IgAVN (3.5 +/- 5.4 mu g/mmol; 25.9 +/- 26.5 mu g/mmol, respectively) compared to both IgAVN (0.4 +/- 0.4 mu g/mmol, P = 0.002; 9.2 +/- 11.5 mu g/mmol, P = 0.004) and HCs (0.3 +/- 0.2 mu g/mmol, P < 0.001; 5.1 +/- 6.0 mu g/mmol, P < 0.001). No statistically significant difference was reported for the plasma concentrations of CFD and CFB. Urinary MASP-1 concentrations were statistically significantly increased in IgAVN (116.9 +/- 116.7 ng/mmol) compared to HCs (41.4 +/- 56.1 ng/mmol, P = 0.006) and plasma MASP-1 concentrations were increased in IgAVN (254.2 +/- 23.3 ng/mL) compared to HCs (233.4 +/- 6.6 ng/mL, P = 0.046).Conclusion. There is evidence of complement pathway products in the urine of children with IgAVN that warrants further investigation