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polysaccharide as phosphocholine, part of the techoic acid of the pneumococcal cell wall, although phosphocholine was the first defined ligand for CRP, a number of 14 other ligands have since been identified. In addition to interacting with various ligands, CRP can activate the classical complement pathway, stimulate phagocytosis, and bind to immunoglobulin receptors (FcγR), (Volanakis and Kaplan, 1971). In humans, plasma levels of CRP may rise rapidly and markedly, as much as 1000-fold or more, after an acute inflammatory stimulus, largely reflecting increased synthesis by hepatocytes. CRP induction is part of a larger picture of reorchestration of liver gene expression during inflammatory states, the acute phase response, in which synthesis of many plasma proteins is increased, whereas that of a smaller number, notably albumin, is decreased. At least 40 plasma proteins are defined as acute phase proteins, based on changes in circulating concentration of at least 25% after an inflammatory stimulus. This group includes clotting proteins, complement factors, anti-proteases, and transport proteins. These changes presumably contribute to defensive or adaptive capabilities (Volanakis and Kaplan, 1971). 1.2.4.1. The structure of CRP CRP consists of five identical, noncovalently associated ∼23-kDa promoters arranged symmetrically around a central pore. The term “pentraxins” has been used to describe the family of related proteins with this structure. Each protomer has been found by x-ray crystallography to be folded into two antiparallel β sheets with a flattened jellyroll topology similar to that of lectins such as concanavalin a (Shrive et el., 1996). Each protomer has a recognition face with a phosphocholine binding site consisting of two coordinated calcium ions adjacent to a hydrophobic pocket. The co-crystal structure of CRP with phosphocholine suggests that Phe-66 and Glu81 are the two key residues mediating the binding of phosphocholine to CRP , Phe66 provides hydrophobic interactions with the methyl groups of phosphocholine whereas Glu-81 is found on the opposite end of the pocket where it interacts with 15 the positively charged choline nitrogen. The importance of both residues has been confirmed by mutagenesis studies (Agrawal et al., 2002). The opposite face of the pentamer is the effector face, where complement C1q binds and Fcγ receptors are presumed to bind. A cleft extends from the center of the protomer to the central pore of the pentamer, and several residues along the boundaries of this cleft have been shown to be critical for the binding of CRP to C1q, including Asp-112 and Tyr-175. The crystal structure of the globular head domain of C1q was recently solved, and a model for C1q binding to CRP was proposed in which the top of the predominantly positively charged C1q head interacts with the predominantly negatively charged central pore of the CRP pentamer, The CRP test is not diagnostic of any condition, but it can be used together with signs and symptoms and other tests to evaluate an individual for an acute or chronic inflammatory condition. For example, CRP may be used to detect or monitor significant inflammation in an individual who is suspected of having an acute condition, such as: A serious bacterial infection like sepsis, fungal infection, pelvic inflammatory disease (Black et al., 2003). The CRP test is useful in monitoring people with chronic inflammatory conditions to detect flare-ups and/or to determine if treatment is effective. Some examples include: Inflammatory bowel disease, some forms of arthritis, autoimmune diseases, such as lupus or vacuities. CRP may sometimes be ordered along with an erythrocyte sedimentation rate (ESR), another test that detects inflammation. While the CRP test is not specific enough to diagnose a particular disease, it does serve as a general marker for infection and inflammation, thus alerting health practitioners that further testing and treatment may be necessary.
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