The Vasculitides
© Dirk Biddle
1.7.14 C-reactive Protein
C-reactive protein (CRP) is an protein of the family. The name C-reactive protein derives from the fact that when it was discovered in 1930, it was reacting with on . CRP is primarily produced by epithelial cells in the liver ( ) in response to the presence of (particularly ). The most important role of CRP is its interaction with the complement system, where not only does CRP act as an , enhancing neutrophil and macrophage phagocytosis of bacteria, parasites, and immune complexes, it also binds to complement, activating it via the classic pathway. Recently CRP has been discovered to also be produced by macrophages in , inducing the further production of (chemotactic non-antibody proteins) and , thereby attracting additional monocytes and thus helping to sustain an ongoing inflammatory reaction.
CRP is considered the most reliable marker of inflammation and studies have proved that quantification of CRP is superior to cytokine measurement (eg; IL-6, IL-ß1, tumor necrosis factors). CRP concentrations are elevated in almost all inflammatory, infectious, and neoplastic diseases. Specific conditions include rheumatologic diseases (eg; Sjögren's syndrome, Systemic lupus erythematosus, Rheumatoid arthritis), most primary vasculitides (although not all), and chronic infections (eg; tuberculosis, endocarditis). The clearance rate of CRP is constant, therefore the level of CRP in the blood is regulated solely by synthesis, and because the acute-phase response is relatively non-specific, the value of measuring acute-phase protein concentrations is to assess the extent of inflammation, reflecting momentary disease activity. Thus also CRP levels may be used to monitor the course of disease in response to therapeutic intervention.
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Acute-phase Protein: These plasma proteins (in addition to fibrinogen) increase 25% or more in response to inflammation and injury are under direct control of interleukin-6 (IL-6) (hepatocyte-stimulating factor).
Other proteins which increase are ceruloplasmin, C3 and C4 which increase 50% or more; alpha-1 acid glycoprotein, alpha-1 antitrypsin, haptoglobin and fibrinogen (the major determinant of viscosity 1 ) which increase two- to fourfold; C-reactive protein (CRP) and serum amyloid A which increase several hundred-fold.
Despite long-held clinical opinion to the contrary, available data indicate that neither ESR nor measurement of specific acute-phase reactants are useful in excluding underlying infection or inflammation regardless of the pretest probability.
These proteins are secreted into the blood in increased or decreased quantities by hepatocytes in response to trauma, inflammation, or disease. They can serve as inhibitors or mediators of the inflammatory processes. Certain acute-phase proteins have been used to diagnose and follow the course of diseases or as tumour markers. (OMD),
Pentraxins: Family of proteins that share a discoid arrangement of five noncovalently linked subunits. Includes CRP and serum amyloid P. (OMD),
Capsular Polysaccharide: Bacterial polysaccharides are usually associated with the outer surface of the bacterium. They can form an amorphous layer of extracellular polysaccharide (EPS) surrounding the cell that may be further organized into a distinct structure termed a capsule. Additional polysaccharide molecules such as lipopolysaccharide (LPS) or lipooligosaccharide (LOS) may also decorate the cell surface. Polysaccharide capsules may mediate a number of biological processes, including invasive infections of human beings.,
Hepatocytes: Any of the polygonal epithelial cells of the liver that secrete bile. (M+),
Cytokine: Substance produced by a leucocyte that acts upon another cell. Small proteins or biological factors (in the range of 5-20 kD) that are released by cells and have specific effects on cell-cell interaction, communication and behaviour of other cells. Not really different from hormones, but the term tends to be used as a convenient generic shorthand for interleukins, lymphokines and several related signaling molecules such as TNF (tumour necrosis factor alpha) and interferons. Generally growth factors would not be classified as cytokines, though TGF is an exception. Rather an imprecise term. Chemokines are a subset of cytokines. (OMD),
Opsonin: Any of various proteins (such as complement or antibodies) that bind to foreign particles and microorganisms (such as bacteria) making them more susceptible to the action of phagocytes. (M+)
Probably the most important in mammals derive from complement (C3b or C3bi) or immunoglobulins which are bound through the Fc receptor. (OMD),
Atherosclerotic Plaques: A buildup of cholesterol and fatty material within a blood vessel due to the effects of atherosclerosis. (OMD),
Chemokine: Cytokines that are chemotactic for leucocytes. The first member of the family was IL-8 (interleukin-8) but subsequently many other members have been identified. They can now be sub divided into two groups on the basis of the arrangement of a pair of conserved cysteines: the C x C group includes platelet Factor 4, platelet basic protein, interleukin 8, melanoma growth stimulatory protein, macrophage inflammatory protein 2. (OMD),
Adhesion Molecules: Molecules that are involved in T helper-accessory cell, T helper-B-cell, and T cytotoxic-target cell interactions.(OMD)
During an inflammatory response adhesion molecules serve to enhance pairing between many less avid receptors and their ligands and transmit signals that direct specific effector functions. At least four superfamilies of adhesion molecules participate in these events: the selectins, the integrins, certain members of the immunoglobulin superfamily and cadherins.
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