Properdin in C3 glomerulopathy

24 p.-3 fig.-3 tab.Properdin (P) stabilizes the alternative pathway (AP) convertases, being the only known positive regulator of complement system. In addition, P is a pattern recognition molecule able to initiate directly the AP on non-self surfaces. Although P deficiencies are long time known to be associated with Neisseria infections and P is often found deposited at sites of AP activation and tissue injury, the potential role of P in the pathogenesis of complement dysregulation associated disorders has not been extensively studied. Serum P levels were measured in 49 patients with histological and clinical evidence of C3 glomerulopathy (C3G). Patients were divided in two groups according to the presence or absence of C3 nephritic factor (C3NeF), an autoantibody that stabilizes the AP C3 convertase. The presence of this autoantibody results in a significant reduction in circulating C3 (p<0.001) and C5 levels (p<0.05), but does not alter factor B, P and sC5b-9 levels. Interestingly, in our cohort, serum P levels were low in 17 of the 32 C3NeF-negative patients. This group exhibited significant reduction of C3 (p<0.001) and C5 (p<0.001), and increase of sC5b-9 (p<0.001) plasma levels, compared to the control group. Besides, P consumption was significantly correlated with C3 (r= 0.798, p 0.0001), C5 (r= 0.806, p<0.0001), sC5b-9 (r = -0.683, p 0.043) and a higher degree of proteinuria (r= -0.862, p 0.013). These results further illustrate the heterogeneity among C3G patients and suggest that P serum levels could be a reliable clinical biomarker to identify patients with underlying surface AP C5 convertase dysregulation.This work was performed with the support of grants from the Spanish Ministerio de Economía y Competitividad (SAF2012-38636), Comunidad de Madrid (S2010/BMD-2316) and CIBERER (ACCI-2014).Peer reviewe