March 10, 2020

The role of the complement system in disease – Too much of a good thing

The complement system is a key component of the body’s innate immune defense. It has an important role as a first-line defense against microorganisms but is also involved in other important functions such as homeostasis, clearance of cellular debris and immune surveillance. Clearly, such a broad range of functions requires a well-balanced interaction with other biological systems in the body. Indeed, the complement system has been likened to a balancing scale that needs to balance between providing sufficient activity to protect the body but not enough to be harmful. A number of genetic and environmental factors can tip the scale from defense to destruction.

March 10, 2020

The role of the complement system in disease – Too much of a good thing

The complement system is a key component of the body’s innate immune defense. It has an important role as a first-line defense against microorganisms but is also involved in other important functions such as homeostasis, clearance of cellular debris and immune surveillance. Clearly, such a broad range of functions requires a well-balanced interaction with other biological systems in the body. Indeed, the complement system has been likened to a balancing scale that needs to balance between providing sufficient activity to protect the body but not enough to be harmful. A number of genetic and environmental factors can tip the scale from defense to destruction.

Disease despite a functioning complement system

Sometimes complement-associated diseases can be connected to deficiencies or disorders in the complement pathways – but not always. Often, the complement system can be fully functional yet still result in hyperinflammation due to exposure to sudden and high levels of inflammation-causing molecules. This mechanism has been described for sepsis, trauma, burns and a few other conditions.

Autoantibody-associated disease

Perhaps the best-known example of a complement-associated disease is Systemic Lupus Erythematosus (SLE). Here, autoantibodies can cause inappropriate complement activation resulting in inflammation and tissue damage as well as deposition of complement activation proteins in the kidneys and other organs. Myasthenia gravis and ANCA-associated vasculitis are other examples of complement disorders that are caused by autoantibodies.

In atypical Hemolytic Uretic Syndrome (aHUS), autoantibodies directed against complement components affect the complement response.

Disease caused by failure to clear debris

Sometimes a failure to clear up cellular debris can cause inappropriate activation of the complement system. Such debris, which can form and accumulate due to lifestyle factors, oxidative stress and aging, can induce inflammation and tissue damage which in turn can fuel other degenerative processes. Alzheimer’s disease, Age-Related Macular Degeneration (AMD) and atherosclerosis are well-known diseases that can result from this process.

Harmful reactions to biomaterials

A new kind of complement-related disorder has emerged with the introduction of polymers and metals in medical devices such as filters, implants and drug delivery systems. The mechanism behind this kind of complement activation varies but often involves plasma proteins binding to the foreign material followed by activation of various complement components.

Disorders caused by dysfunctional complement components

There are many known deficiencies in key complement components, some of which have clear roles in disease. Deficiencies in C1, for example, often results in SLE-like symptoms in patients. C3 deficiency is associated with increased susceptibility to bacterial infections and other complement components have been connected to kidney disease. Version 3 of the Database of complement gene variants contains over 8000 total entries and over 800 disease entries.

The complement system is very complex, with many components, functions and crosstalk to other biological systems. It is involved in a constant balancing act to keep the activity at an appropriate level – too little can leave the body vulnerable to disease and too much can cause harm. Complement activity can truly be too much of a good thing...

What we offer?

Svar has over 15 years’ experience of complement system assay development. Our complement system assays have been developed by our experienced scientists in close collaboration with key opinion leaders, to yield sensitive, reliable and easy-to-use products for the exploration of most aspects of the complement system.     

The Svar Complement activity biomarkers give valuable intelligence in several situations where one might suspect that complement activation plays a role in the disorder. They are developed to target the unique neoepitopes only presented at the complement component or complex when activated. 
 
Take advantage of our complement expertise and let us guide you on the Complement Pathway!

 

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