What is being tested?
The complement system consists of almost 60 proteins, approximately 30 of which are circulating blood proteins that work together to promote immune and inflammatory responses. Complement tests measure the amount or activity of complement proteins in the blood.
The complement system’s principal role is to help identify, destroy and remove foreign pathogens like bacteria and viruses, as well as damaged “self” materials (e.g., cells and proteins). The complement system is so named because it “complements” or aids the natural body defenses, such as antibodies. So, the complement system is also activated when the body makes antibodies, whether against itself or foreign invaders. The body makes antibodies against its own tissues that it thinks are foreign (autoantibodies) in various autoimmune diseases.
The complement system is part of the body’s innate immune system. Unlike the acquired immune system, which produces antibodies that target and protect against specific threats, the innate immune system is non-specific and can quickly respond to foreign substances. It does not require previous exposure to an invading microbe or offending substance and does not maintain a memory of previous encounters.
There are nine primary complement proteins that are designated C1 through C9. These components, in addition to the remaining proteins, work together in a cascade-like approach by activating, amplifying, breaking apart, and forming protein complexes that respond to infections, “non-self” tissues (e.g., transplants), dead cell debris (e.g., from apoptosis), or inflammation.
The complement cascade consists of 3 separate pathways that may be activated to converge in a final common pathway. The pathways include the “classical pathway” (including components C1qrs, C2, C4), the “alternative pathway” (including components C3, factor B, properdin), and the “lectin pathway” (a.k.a. mannan-binding lectin [MBL]). The end result of all three activation pathways is the same – the formation of the membrane attack complex (MAC). Complement activation causes several things to happen (“complement cascade”):
- The MAC binds to the surface of each microbe, abnormal cell, or substance that has been targeted for destruction. It creates a lesion (hole) in the membrane wall and causes lysis, which is destruction of the cell by letting the contents out – like piercing a water-filled balloon.
- It increases the permeability of blood vessels, allowing infection-fighting white blood cells (WBCs) to move out of the bloodstream and into tissues.
- It attracts WBCs to the site of the infection.
- It stimulates phagocytosis, a process in which microbes are engulfed by macrophages and neutrophils and killed.
- It also labels immune complexes with complement components so that WBCs will engulf them and clear them out of the blood.
Complement tests measure the amount or the function (activity) of complement proteins in the blood. Complement components may be measured individually or together to determine whether the system is functioning normally. C3 and C4 are the most frequently measured complement proteins. Total complement activity can be measured if a health care practitioner suspects a deficiency that is not measured by C3 or C4. The CH50 functional test measures the function of the complete classical complement pathway, mediated by components C1 – C9. If this measurement is outside the normal range, then each of the nine different complement levels can be measured individually to look for hereditary or acquired deficiencies.