Study Links Low Serum C3 Levels at Time of Diagnosis to Worse Prognosis in AAV Patients

Low blood levels of C3 protein at time of diagnosis are associated with poorer outcomes in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), a Croatian study shows.

The study, “Serum C3 complement levels in ANCA associated vasculitis at diagnosis is a predictor of patient and renal outcome,” appeared in the Journal of Nephrology.

Many recent studies have focused on the role of the alternative complement pathway (aCP) in AAV. This pathway is related to the immune system and functions in destroying foreign pathogens. C3 and C5 are major components of aCP.

Studies have shown an overactivation of aCP in patients with AAV, which contributes to the autoimmunity that characterizes the disease. Such research has already led to the development of an anti-C5a receptor inhibitor, now being evaluated in clinical trials. It has shown promise in improving the condition of AAV patients with AAV. However, no studies have yet evaluated the effect of complement C3 as a marker of prognosis in AAV patients.

That led researchers at Dubrava University Hospital in Zagreb to investigate whether patients with low levels of serum complement C3 have a worse prognosis in the long term.

Researchers recruited 75 patients with AAV and measured their serum C3 levels at the time of diagnosis. Then they split the patients into two groups: one had C3 levels lower than 0.9 g/l, and the other had normal serum C3 levels ranging between 0.9 and 1.8 g/l.

Researchers then determined the association between serum C3 levels and the combined and separate effects on patient survival and renal survival. Renal involvement in patients with AAV is known to be associated with severe AAV and is a major prognostic marker.

Results showed that patients with low levels of serum C3 were 3.1 times more likely to die or progress to end-stage renal disease. When adjusted for other factors, low serum C3 levels were still associated with a 2.8-fold worse patient and renal survival than patients in the normal C3 group.

When looking at the individual effect on patient survival and renal survival, patients with low serum C3 levels were 4.3 times more likely to have a poor survival and 3.6 times more likely to have poor renal survival, compared to patients in the normal C3 level group, after  adjusting for other factors.

This study did not a shown significant association between low C3 levels and any particular subtype of AAV or ANCA-positivity and negativity. The authors did, however, find a significant relationship between patients with normal C3 levels and a higher prevalence of arterial hypertension, an association that has been previously shown in literature.

“We suggest that serum C3 levels should be regularly assessed in all AAV patients at the time of diagnosis and that further research should determine whether the C3 levels are indeed an independent predictor of outcome in AAV,” researchers concluded.