Introduction and Aims: In SLE patients, and particularly in lupus nephritis (LN),aberrant complement activation leads to inflammatory injury , and fluctuation of serum C3 and C4 are a commonly used clinical biomarker of SLE disease activity. However recently a relationship between the complement activation route and clinical manifestations has been hypothesized. Serum C4 consumption,reflecting complement classical pathway (CP) is considered to play a protective role in LN because it favors immunocomplexes removal. Differently an insistent alternative pathway (AP) overactivation, grossly marked by a persistent serum C3 reduction, would play an unnecessary and possibly negative powerful inflammation, thus determining a worse renal prognosis. To enforce this hypothesis recently it was documented that polymorphisms regarding CFH, a relevant protein involved in complement AP regulation, seems to be associated with SLE appearance.
Aim of this study was to identify a subgroup of LN with isolated persistent serum C3 reduction and to evaluate if this cohort had a worse renal prognosis in the long term follow up.
Methods: We examined our series of consecutive patients diagnosed with kidney biopsy as having LN between 1995 and 2013. We evaluated complement status before and after 1 and 6 months of treatment and compared the isolated reduced sC3 group (<C3) with the other patients ( <C3-C4, <C4 and normal group) .
Results: We identified 50 patients with biopsy proven LN. 39/50 had repeated serum complement evaluations. Before treatment 13/39 (33%) patients had an isolated serum C3; after 6 months of immunosuppressive treatment 5 of the <C3 group and 5 of the <C3C4 group had an isolated persistent C3 reduction (pers<C3) (Figure 1).
pers<C3 group shows a significantly worse renal prognosis than the other groups (Figure 2).
Conclusions: Our data shows that a subgroup of LN patients(25%) shows a persistent isolated serum C3 reduction despite immunosuppressive treatment, while serum C4 returns easily into normal values. Persistent serum C3 reduction is associated with a poor renal prognosis.
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