Serum Amyloid P Component (SAP) Interactome in Human Plasma Containing Physiological Calcium Levels

Abstract

The pentraxin serum amyloid P component (SAP) is secreted by the liver and found in plasma at a concentration of approximately 30 mg/L. SAP is a 25 kDa homopentamer known to bind both protein and nonprotein ligands, all in a calcium-dependent manner. The function of SAP is unclear but likely involves the humoral innate immune system spanning the complement system, inflammation, and coagulation. Also, SAP is known to bind to the generic structure of amyloid deposits and possibly to protect them against proteolysis. In this study, we have characterized the SAP interactome in human plasma containing the physiological Ca concentration using SAP affinity pull-down and co-immunoprecipitation experiments followed by mass spectrometry analyses. The analyses resulted in the identification of 33 proteins, of which 24 were direct or indirect interaction partners not previously reported. The SAP interactome can be divided into categories that include apolipoproteins, the complement system, coagulation, and proteolytic regulation.

Serum amyloid P deposition is a sensitive and specific feature of membranous-like glomerulopathy with masked IgG kappa deposits

“…5 Although the exact function of SAP is unclear, it is known to interact in plasma with a wide variety of proteins, including complement components, apolipoproteins, and regulators of coagulation and proteolysis. 6 It forms stable calcium-dependent interactions with its ligands, including proteins, lipoproteins, and DNA, protecting them against degradation. SAP serves as a soluble pattern-recognition molecule involved in the innate immune response, recognizing a variety of pathogen-and damage-associated molecular patterns, including microbial components and apoptotic cell debris.…”

“…An alternative explanation is that IgG kappa is present as c l i n i c a l i n v e s t i g a t i o n a result of a normal interaction between these 2 proteins rather than an autoimmune antigen-antibody interaction, as Ig kappa chain is known to be a part of the normal interactome of serum SAP. 6 Therefore, although useful for tissue diagnostics of this entity, testing for SAP antibodies in the serum does not serve as a noninvasive diagnostic at this time, and the underlying driver of this disease remains a mystery.…”

“…The presence of SAP in the deposits raises new possible explanations for this phenomenon in cases of MGMID. For example, interactions of the SAP protein are known to be heavily Ca 2þ -dependent, 6 and many of the transport media and buffers used in the processing of renal biopsy tissue for immunofluorescence are devoid of Ca 2þ . This in vitro absence of Ca 2þ could result in disruption of immune deposits so that they are no longer available for detection by immunofluorescence on the frozen tissue.…”

Serum Amyloid P and IgG Exhibit Differential Capabilities in the Activation of the Innate Immune System in Response to Bacillus anthracis Peptidoglycan

“…Nevertheless, these data do not exclude SAP interaction with upstream complement components to enhance opsonization of PGN. In fact, a recent report shows that SAP interacts with multiple upstream components of the complement cascade ( 28 ). Consistent with the latter study, we found that depletion of SAP also led to partial depletion of C1q.…”

TMT-Based Proteomic Analysis of Plasma from Children with Rolandic Epilepsy

“…Serum amyloid P-component (APCS) showed increase expression in the plasma of patients with epilepsy. Serum amyloid P-component belongs to the group of short pentraxins in the pentraxin family, which is known to be involved the humoral innate immune system spanning the complement system, inflammation, and coagulation [ 25 ]. Urbanyi et al demonstrated that serum amyloid P-component induced neuronal apoptosis through penetrating the plasma membrane and translocating selectively into the nuclei of neurons [ 26 ].…”