Complement testing in the clinical laboratory

Abstract

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.

Keywords:

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

Disclosure statement

MAVW is employed by the Mayo Clinic, Chair of the Clinical Diagnostic Immunology Division of the American Association for Clinical Chemistry (CDID-AACC), and Councilor of the Association of Medical Laboratory Immunologists (AMLI). In addition, MAVW has intellectual property on the measurement of therapeutic monoclonal antibodies by LC-MS/MS (US patent 42580). MAVW reports research grants in the last 24 months from Sebia Inc. Siemens Healthineers and The Binding Site, outside of this work.

KMPB is employed by the Mayo Clinic and reports no conflict of interest.

AMM is employed by Mayo Clinic and is the Chair of the joint College of American Pathologists/American College of Medical Genetics and Genomics Biochemical and Molecular Genetics Committee.

DHJ is employed by the University of Colorado and reports no conflict of interest.

AFA is employed by the University of Colorado and is Co-Chair of the International Complement Society (ICS) Committee on Quality and Standardization of Complement analysis and Member of the ICS, the Association of Medical Laboratory Immunologists (AMLI), the American Association for Clinical Chemistry and the American College of Toxicology. AFA also consults for the following companies with the funds flowing to the University of Colorado School of Medicine: Apellis, BioCryst, Catalyst, and Ionis.