Complement testing in the clinical laboratory

Maria Alice V. Willrich, Karin M.P. Braun, Ann M. Moyer, David H. Jeffrey, Ashley Frazer-Abel

Research output: Contribution to journalReview articlepeer-review


The complement system is the human’s first line of defense against microbial pathogens because of its important housekeeping and infection/inflammation roles. It is composed of a series of soluble and cell-bound proteins that are activated in a cascade effect, similar to the coagulation pathways. There are different pattern recognizing molecules that activate the complement system in response to stimuli or threats, acting through three initiation pathways: classical, lectin, and alternative. All three activation pathways converge at the C3 component and share the terminal pathway. The main outputs of the complement system action are lytic killing of microbes, the release of pro-inflammatory anaphylatoxins, and opsonization of targets. Laboratory testing is relevant in the setting of suspected complement deficiencies, as well as in the emerging number of diseases related to dysregulation (over-activation) of complement. Most common assays measure complement lytic activity and the different complement component concentrations. Specialized testing includes the evaluation of autoantibodies against complement components, activation fragments, and genetic studies. In this review, we cover laboratory testing for complement and the conditions with complement involvement, as well as current challenges in the field.

Original languageEnglish (US)
Pages (from-to)447-478
Number of pages32
JournalCritical reviews in clinical laboratory sciences
Issue number7
StatePublished - 2021


  • Complement system
  • complement deficiency
  • complement dysregulation
  • laboratory testing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Clinical Biochemistry
  • Biochemistry, medical


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