Complement factors as biomarkers in ANCA-associated vasculitis in remission

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare, autoimmune diseases causing inflammation in the vessel wall. Many organs can be affected, and kidney involvement is a common and serious manifestation. Complement activation is important in disease development and has also been detected in patients in remission. The reason for increased complement activation also without active disease is not understood.

In this study, 65 AAV patients in remission, contributing with a total of 147 plasma samples, were included. Biomarkers of complement activation such as C4d (classical and lectin pathways), C3bBbP (alternative pathway), and soluble terminal complement complex (sTCC) (common terminal pathway) were measured with ELISA. For C4d measurement, an improved assay with an antibody targeting a cleavage neoepitope solely exposed during complement activation was used.

Our first hypothesis was that patients prone to recurrent flares might have an increased complement activation even when beeing in remission. However, we found no significant difference between those who did and did not develop flares during follow-up, nor any correlation between the total number of flares and any of the complement biomarkers. Interestingly, higher sTCC levels in remission correlated significantly to kidney involvement at the time of diagnosis and plasma creatinine levels at the time of sampling. Also, the diagnosis of microscopic polyangiitis (MPA), compared to granulomatosis with polyangiitis (GPA), yielded higher sTCC levels, and plasma C-reactive protein levels correlated significantly to sTCC.

These findings suggest that persistent complement activation during remission in AAV may reflect underlying disease severity and organ involvement rather than predicting future flares.