Introduction
Properdin is a plasma glycoprotein, which is the only known positive regulator of the complement by stabilizing C3 (C3bBb) and C5 ((C3b)2-nBb) convertases of the alternative pathway [1]. Under physiological conditions it is found to form cyclic dimers (P2), trimers (P3) and tetramers (P4) as the convertase-stabilizing activity of the tetramer is greater than the trimer [2-4].
Along with its stabilizing role for the C3 convertase, it has been shown that properdin could act as a pattern recognition molecule. Several authors have reported that properdin can recognize structures, independent of C3, like glycosaminoglycans on tubular cells leading to complement activation [5]; microbial surfaces, apoptotic and necrotic cells, providing a platform for C3 convertase assembly [6-9]. The pattern recognition role remains controversial since other authors have reported that properdin was only able to bind structures in C3-dependent manner [10].
The role of properdin in complement-mediated diseases still is not clear. Properdin deficiency contributes to infectious and non-infectious diseases in various models [11-13]. Moreover, properdin is detected in kidney biopsies and in serum/plasma/urinary samples from patients with various complement-mediated renal diseases [14]. For example, in patients with membranoproliferative glomerulonephritis and lupus nephritis (LN) were detected low serum levels of properdin but properdin depositions in glomeruli, implying that low properdin levels may be due to hypercatabolism [15]. SLE patients with low plasma levels of C3 have also low plasma levels of properdin [16]. Few studies report isolated cases of anti-properdin autoantibodies in different pathological contexts. Józsi et al., 2014 demonstrated weak antibody positivity to properdin, C3b, and Factor B – to all components of the convertase – in patients with dense deposit disease (DDD) [17]. Anti-properdin antibodies were found also in a patient with LN, carrying heterozygous C3 mutation, together with autoantibodies against others complement alternative pathway proteins – Factor I, Factor B, and C3 [18]. Functional assays showed that all these autoantibodies cause alternative pathway activation, which could contribute to the tissue damage in kidney of the patient. Tanuma, et al., 1990 found in sera from patients with membranoproliferative glometulonephritis (MPGN) and Dense Deposit Disease (DDD), C3 Nephritic Factor (C3NeF:P), which displayed the properties of properdin and IgG. The authors consider that C3Nef:P is an immune complex of IgG autoantibody against properdin and properdin [19].
Since LN affects the course of the disease, quality of patient’s life and the prognosis of SLE [20-22], there is an unmet need of more efficient biomarkers for early diagnosis, to more precisely evaluate the disease activity, the degree of disease severity and the response of therapy. Here we show that autoantibodies against properdin exist in about 20% of the LN patients, potentiating its activity. Although likely not a driver of the disease, these autoantibodies may be a contributing factor with pathological relevance for LN.