Why are complement activity markers valuable?

During the last decade, the importance of the complement system has become evident in both clinical medicine and complement therapeutics. This increased interest means a more prominent need for assays to evaluate complement activity. 

Activity markers are used to determine whether deficiencies, overactivation or dysregulation in the complement system are causing, or contributing to, a person's disease or condition.

In order to exactly measure such activation, assays for quantification of products formed during activation are required.

 

Svar Complement Activity Markers 

The Svar Complement activity markers give valuable intelligence in several situations where one might suspect that complement activation plays a role in the disorder. An important aspect when using complement activity markers to evaluate a pathological condition is only measure the specific activated protein. Therefore, the Svar assays for complement activity markers are developed to target the unique neoepitopes only presented at the complement component or complex when activated. 

C4d

plays a prominent role in transplantation and autoimmunity

C4d has the potential to detect patients at risk for the consequences of antibody-mediated disease and the development of new therapeutics that block complement activation makes C4d a marker with potential to identify and monitor patients who may possibly benefit from these drugs.

Stable marker associated with transplant rejection

C4d has been recognized as a biomarker for its stability and strong association with antibody mediated rejection of grafts. C4d in plasma is now increasingly identified as a biomarker for complement activation and as a tool to predict and monitoring flares in for example SLE, Systemic sclerosis and ANCA–associated vasculitis. 

Useful biomarker within the cancer area 

C4d may be of both diagnostic and prognostic value in lung cancer, differentiation of individuals with indeterminate lung nodules and for malignant pleural mesothelioma correlate with tumor load and primary tumor load and chemotherapeutic response. 

TCC

for general evaluation of complement activation

Measuring TCC levels can be very informative as a supplement to functional assessment of the three complement pathways. As a product of the terminal pathway, TCC can be a result from all three complement activation pathways,  and reflects the historical in vivo activity of complement in a given sample.

Enabling effective treatment

Increased levels of TCC can be  detected in both acute injury and inflammation like trauma and sepsis and in chronic inflammation and diseases like hemolytic uremic syndrome (HUS), Systemic lupus erythematosus (SLE), ANCA associated vasculitis and rheumatoid arthritis (RA). 

Preventing adverse reactions 

The complement system can also be activated by artificial surfaces, for example during hemodialysis or cardiopulmonary bypass, resulting in increased levels of TCC. TCC is therefore well suited for studies of complement activation by biomaterials in medical devices and part of the recommended tests for assessing complement activation according to ISO standard 10993-4 for hemocompatibility testing. 

HEMOCOMPATIBILITY

Providing safer treatment

Hemocompatibility testing is essential for evaluating interactions of foreign material having contact with blood.

Complement activity markers such as TCC are recommended to predict possible adverse reactions from medical devices such as grafts, stents, hemodialysis and cardiopulmonary bypass but also to biological drugs and nanomedicines. 

 

DRUG SAFETY

Preventing adverse reactions

As many as 500 000 patients in the USA each year are affected by adverse reactions that might be complement activated. These reactions are critical and can lead to death.

TCC can be used successfully for investigation to rule out if a drug is toxic or if a reaction is due to other related issues such as “infusion reactions”. Infusion reactions has been reported to several biopharmaceuticals and nanomedicines.

"Pathologically increased complement activation can indirectly be evaluated by quantification of complement components, but in order to exactly measure such activation, assays for quantification of products formed during activation are required."

(Bergseth G et al, 2013)