Mining the complement system for lupus biomarkers

Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease. Activation of the complement system plays a fundamental role in the pathogenesis of SLE. For the past several decades, laboratory monitoring of SLE has focused primarily on measurement of serum C3, C4, and their activation products. However, the utility of these measures as biomarkers for diagnosis and assessment of disease activity of SLE is still debated. Over the same time span, knowledge of the complement system has advanced remarkably, with more than 30 proteins identified. In view of the urgent need for identifying reliable lupus biomarkers, it is appropriate to revisit the issue of whether the complement system is a potential source of biomarkers for SLE. This article will review historical aspects of complement measurement in SLE, and summarize recent advances that may lead to a newly rejuvenated “gold rush” to mine the complement system for biomarkers of SLE. Specifically, development and utility of a novel assay that measures cell-bound complement activation products as lupus biomarkers will be discussed.