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.