Complement deficiency

Complement cascade can be triggered by classical (antibody binding to antigen, but also directly by C-reactive protein an other substances), lectin (mannan binding lectin, which recognise glycoproteins not typically found in higher order animals) or alternative pathways.  The alternative pathway is the oldest, and constitutes a constant low level autoactivation, at the ready to explode!  Properdin acts here, and may ineract directly with bacteria.

Deficiency can cause susceptibility to infection, but see also hereditary angioedema and atypical HUS.

C3 is the common factor, so deficiency leads to severe infection with encapsulated organisms eg Pneumococcus, Haemophilus, Meningococcus.  Deficiency in terminal and alternative pathways lead almost exclusively to problems with meningococcus!

Properdin

Stabilizes C3/C5 convertase enzymes.  Deficiency (X-linked) associated with fulminant meningococcal infection, especially with unusual types eg W135, Y!  Phagocytosis more important for type B disease? Life time risk for affected individual is about 50%!  Interestingly, mean age of presentation is 14yrs.  Recurrence is actually unusual, presumably due to intact immune memory.

Subtypes characterized by absent, low level and dysfunctional properdin seen.  Standard screening with C3, C4 and CH50 are normal.  Good family history is more important.

Good antibody responses to Men ACWY vaccine.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905414/

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952982/

 

https://www.ncbi.nlm.nih.gov/pubmed/19758139