Serum Amyloid A: Where next for this biomarker?

SAA is a major acute phase protein. Secreted in response to inflammation caused by infection the levels of this apolipoprotein rise rapidly and quickly fall following successful treatment. Analysis of this biomarker thus offers real time information on the state of inflammation by use of a simple blood test.

As part of the acute inflammatory response SAA is responsible for attracting immune cells to the site of inflammation and the induction of enzymes to degrade the extracellular matrix to allow remodelling at the site. The production of this acute phase protein is stimulated by proinflammatory cytokines, such as IL-6, IL-1, TNF-?, IFN-? and TGF-?, reaching 1000-fold greater than normal levels within 5-6 hours from induction. It is produced primarily by the liver, though extrahepatic production of SAA by several tissues and cell types has been described in patients with chronic diseases including Alzheimer’s disease, cancer, diabetes, obesity, and atherosclerosis.
Clinicians and veterinarians are now using the presence of this biomarker as an indicator of infection, allowing them to quickly diagnose and monitor the efficacy of treatment.
In chronic conditions, such as rheumatoid arthritis, elevated levels of SAA have been shown to be a more sensitive marker in showing the extent of inflammation than the gold standard C-reactive protein. Not only does the presence of this inflammatory biomarker reveal the current level of inflammation in rheumatoid arthritis patients, it has also been associated with cardiovascular problems and renal involvement. Monitoring the levels of SAA in patients with chronic inflammatory conditions, such as rheumatoid arthritis, may help to identify those at risk of persistent inflammation and extra-articular complications.
SAA screening is becoming increasingly common in equine medicine to track infection and the efficacy of treatment. In the face of infection SAA levels begin to rise almost immediately. The response is faster than other markers typically screened for and the sensitivity of SAA to onset, duration and the end of the disease process mean that the use of this biomarker allow not only earlier treatment, but the efficacy of treatment and the correct time to discontinue treatment to be gauged by vets.
Chronic inflammatory conditions such as rheumatoid arthritis could be more effectively treated with improved screening of biomarkers such as SAA
Chronic inflammatory conditions such as rheumatoid arthritis could be more effectively treated
While the identification and adoption of biomarker screening for different disease processes offers hope to many – for both early detection and as more personally tailored treatment, complications with assay development have hindered their use in the clinic. Bottlenecks exist in affinity reagent development, platform sensitivity and reproducibility and Affimer technology may be able to unblock these bottlenecks in the integration of biomarker screening to the clinic.
Affimer reagents are small engineered affinity proteins that can be developed to specifically bind any target with high affinity, but without the long lead times associated with custom antibodies. With a custom turnaround time of just 7 weeks and consistent batch reproducibility these affinity reagents are biologically inert and biochemically stable, and are very robust showing no loss of activity when bound to solid surfaces.
Professor Ann Morgan, a consultant rheumatologist at Leeds University has already used Affimer technology to identify molecular signatures that allow the delineation of different inflammatory conditions, such as rheumatoid arthritis, psoriatic arthritis, SLE and giant cell arteritis, and is hoping to further this work in the development of Affimer-based therapeutics.
Further questions surrounding SAA that still need answering include: Which inflammatory conditions increase SAA? How are SAA levels affected by surgery? Does SAA differentiate between inflammation that is infectious vs. non-infectious? Can SAA be targeted in the treatment of chronic inflammatory diseases? With Affimer technology as part of the researchers toolkit questions like these may soon be answered.