properdin

Properdin is a positive regulator of the complement system, specifically the alternative pathway. It stabilizes the C3 convertase on microbial and some damaged surfaces, by binding to the C3bBb complex and increasing its half-life from roughly tens of seconds to several minutes. This stabilization enhances downstream complement amplification and opsonization. Properdin can also recognize certain microbial surfaces and contribute to initiating alternative pathway activation on those surfaces, though it does not by itself initiate convertase formation in fluid phase.

Structure and sources: In human plasma properdin exists predominantly as oligomers, including dimers (P2), trimers (P3), and tetramers (P4), with molecular weights spanning approximately 100 to 500 kDa. It is produced mainly by neutrophils and is stored in their granules, from which it is released upon activation; other myeloid cells, such as monocytes and dendritic cells, contribute to plasma properdin as well. The liver is not a major source of circulating properdin.

Clinical relevance: Properdin deficiency is a rare, X-linked condition that increases susceptibility to infections with encapsulated bacteria, particularly Neisseria meningitidis. Deficiency disrupts stabilization of the C3 convertase, weakening the alternative pathway’s opsonizing and lytic responses.

Therapeutic context: Because properdin amplifies the alternative pathway, pharmacologic inhibition of properdin is being explored as a strategy to reduce pathological complement activation in diseases such as age-related macular degeneration and certain C3 glomerulopathies. Such approaches aim to dampen overactive complement while balancing infection risk.