Pentraxins family of proteins acquired the name from their ability to form pentameric (or decameric) structures formed by non-covalent interactions. C-reactive protein (CRP or PTX1; mature chain 206 aa; chromosome 1q21-23) nonglycosylated, ~24 kda monomer and ~118 kda pentamer) is a ubiquitous protein found in both vertebrates and invertebrates. Originally CRP was defined as a substance, observed in the plasma of patients with acute infections, that reacted with the C polysaccharide of the pneumococcus. It is one of the plasma proteins that are called acute phase reactants because of a pronounced rise in concentration after tissue injury or inflammation; in the case of CRP the rise may be 1000-fold or more. CRP is composed of 5 identical, 21,500-molecular weight subunits. It is detectable on the surface of about 4% of normal peripheral blood lymphocytes. Acute phase reactant CRP is produced in the liver; those cells produce CRP detectable on lymphocytes.

It has been proposed that the function of CRP relates to its ability to recognize specifically foreign pathogens and damaged cells of the host and to initiate their elimination by interacting with humoral and cellular effector systems in the blood. CRP binds with high affinity to chromatin. It has been proposed that one of its major physiologic functions is to act as a scavenger for chromatin released by dead cells during the acute inflammatory process. Thus, the CRP molecule has both a recognition and an effector function.

More recently, it has been shown that minor elevations of C-reactive protein are predictive of cardiovascular events in patients with coronary heart disease. C-reactive protein not only may be a marker of low-grade chronic systemic inflammation but also may be directly involved in atherosclerosis. It can amplify the antiinflammatory response through complement activation, tissue damage, and activation of endothelial cells. In a recent

study of 27,939 apparently healthy American women who were followed for a mean of 8 years, C-reactive protein and low density lipoprotein cholesterol levels in the prediction of first cardiovascular events. These data suggested that the CRP level is a stronger predictor of cardiovascular events than the high density lipoprotein cholesterol level and that it adds prognostic information to that conveyed by the Framingham risk score.

Serum amyloid P component or SAP or APCS, or PTX2 (mature chain 204 aa, chromosome 1q21-23) with which CRP has about 59% homology, is situated in the same area of chromosome 1. SAP is universally present in amyloid deposits 9senile plaque and neurofibrially tangels) in Alzheimers patients. SAP levels in CSF can be useful for assessing cognitive impairment in AD patients. However, SAP appeared not to be required for A-beta deposition since no endogenous SAP immunoreactivity was found in mice overexpressing APP.

In mice with a targeted deletion of the SAP gene, induction of reactive amyloidosis was retarded, demonstrating the participation of SAP in pathogenesis of amyloidosis in vivo and confirming that inhibition of SAP binding to amyloid fibrils is an attractive therapeutic target. SAP knock out mice develop antinuclear autoimmunity and glomerulonephritis. However the exact role of SAP in SLE is not clear. SAP also neutralizes LPS and it is potentially useful in defense against serious gram-negative sepsis.

Novel members of the prototypic CRP/pentaxin family have been identidied that share some sequence homology and a general protein structure. These include PTX3 or TSG14 or long penetraxin, neural pentraxins, NPX1, NPX2, and the receptor termed called NPXR. Antibodies to these proteins are also available.