Serum Amyloid P (SAP) is a protein naturally present in the bloodstream. Produced by the liver, it belongs to the pentraxin family of proteins, named for their characteristic five-subunit, pentagonal structure. In healthy individuals, SAP circulates at a relatively stable concentration and performs regular functions within the body.
Normal Functions of Serum Amyloid P
As a component of the body’s innate immune system, Serum Amyloid P (SAP) has several protective roles. Its primary function is to bind to various molecules in a calcium-dependent process, including DNA from dead cells and pathogenic microorganisms. By attaching to this cellular debris, SAP facilitates its clearance, which prevents the immune system from attacking the body’s own components. This removal is aided by SAP’s interaction with macrophages, immune cells that engulf and digest tagged cellular waste.
SAP also interacts with the complement system, a network of proteins that enhances the immune response. It binds to complement component C1q to help activate the classical complement pathway. This activation further promotes the clearance of pathogens.
Serum Amyloid P’s Role in Disease
In certain diseases, the normal functions of Serum Amyloid P (SAP) are subverted, most evidently in amyloidosis. This group of disorders involves proteins misfolding into insoluble structures called amyloid fibrils. These fibrils accumulate in tissues and organs, disrupting their function.
SAP binds to all known types of amyloid fibrils, regardless of the protein that formed them. Once bound, SAP becomes a universal component of these deposits, making them resistant to being broken down by the body. By protecting the fibrils from degradation, SAP contributes to their persistence and accumulation.
SAP itself does not form the primary fibril structure. Instead, it acts as an accessory molecule that attaches to fibrils after they form, shielding them from clearance. This stabilizing effect exacerbates the severity of amyloid diseases and can affect organs such as the kidneys, liver, and heart.
Studies in animal models have confirmed SAP’s role in promoting the disease. The absence of SAP was shown to significantly slow down the development of experimental amyloidosis.
Measuring Serum Amyloid P Levels
The concentration of Serum Amyloid P (SAP) in the blood is measured to help diagnose and monitor systemic amyloidosis. This is done using an immunoassay, such as an ELISA, which uses antibodies to determine SAP’s concentration from a blood sample.
In healthy individuals, SAP circulates at a concentration of around 30-40 micrograms per milliliter. While SAP levels can rise with inflammation, the response is less dramatic than other markers like C-reactive protein. Its clinical use is therefore focused on conditions involving amyloid deposits.
A specialized diagnostic application is SAP scintigraphy, a nuclear imaging technique. A small amount of the patient’s SAP is extracted, tagged with a radioactive tracer, and injected back into the bloodstream. The radiolabeled protein then accumulates in organs and tissues affected by amyloidosis because SAP specifically binds to these deposits.
A subsequent scan visualizes these areas, providing a whole-body map of amyloid deposits. This non-invasive method is highly specific for diagnosing systemic amyloidosis and revealing the extent of organ involvement. Serial scans can also monitor disease progression or assess treatment effectiveness.
Targeting Serum Amyloid P in Medicine
The discovery of Serum Amyloid P’s (SAP) role in stabilizing amyloid deposits led to therapies that target this protein. The goal is to remove SAP from the body, making the amyloid fibrils vulnerable to natural clearance mechanisms. This allows the body’s immune cells to access and break down the harmful protein aggregates.
One therapeutic approach uses a drug called miridesap (CPHPC). Miridesap binds to SAP in the bloodstream, forming a complex that is rapidly cleared by the liver. This process depletes circulating SAP, preventing it from binding to and protecting amyloid deposits.
A second strategy combines miridesap with a monoclonal antibody called dezamizumab. After miridesap lowers circulating SAP levels, dezamizumab is administered. This antibody specifically targets the SAP that remains bound to amyloid fibrils in the tissues.
The antibody’s binding to SAP on the deposits acts as a flag for the immune system. This triggers a response from macrophages, which then engulf and destroy the amyloid. Clinical trials have shown this combination therapy can lead to the clearance of amyloid from organs like the liver and spleen.