Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium

What is it about?

In this paper we summarize the most important observations of a two year project that aimed the development of novel diagnostics for lupus (SLE). We report serological and genetic markers and their interactions in lupus. It has been known that complement C4 and C3 levels decrease in lupus due to consumption. Unexpectedly, complement is fully capable to react with nucleic acids in the sera of SLE patients, but not so with different types of molecules. Measurement of complement binding to nucleic acids could therefore be used for diagnostic purposes. A genetic factor, a mutation in a complement receptor, is associated with a different serological profile in lupus patients, pointing to the role complement plays in lupus.

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Why is it important?

The finding that complement binding to nucleic acids is very strong in spite of decreased serum complement levels is unexpected. This shows that antibodies targeting nucleic acids can induce opsonization by complement even when complement levels are decreased. Thus, instead of measuring indirect consequences of antibody binding to targets and consuming complement it is possible to measure directly the effects of antibodies binding to autoantigens containing nucleic acids. This can be a novel diagnostic approach.

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