CRP C-Reactive Protein

CRP One of many Acute Phase Proteins Produced in response to trauma, tissue damage, infection and inflammation Produced in response to trauma, tissue damage, infection and inflammation Most are made in the liver as a result of increased synthesis and secretion Most are made in the liver as a result of increased synthesis and secretion The monitoring of an acute phase response can reflect the extent and activity of an ongoing problem and can be used to monitor response to therapy The monitoring of an acute phase response can reflect the extent and activity of an ongoing problem and can be used to monitor response to therapy

CRP

CRP Five identical polypeptide units Five identical polypeptide units Reference Range <10 mg/L Reference Range <10 mg/L Half Life 8 hours Half Life 8 hours Rises within a few hours of insult or injury Rises within a few hours of insult or injury

CRP 3 main group of APP 3 main group of APP 1. Those that show a 50% increase in levels Eg. Ceruloplasmin 2. Those that show a 2-4 fold increase Eg. Fibrinogen, haptoglobin  3. Those that show a several hundred fold increase Eg. CRP

Activation Once CRP has bound to a ligand, C1q attaches and activates the complement cascade Once CRP has bound to a ligand, C1q attaches and activates the complement cascade CRP is also able to bind FcγRI and FcγRII CRP is also able to bind FcγRI and FcγRII These two immunoglobulin receptors create responses from phagocytic cells These two immunoglobulin receptors create responses from phagocytic cells

What does CRP bind to? CRP has the highest affinity for phosphocholine on bacteria or as a mixture of sphingomyelin and phosphatidylcholine in eukaryotic membranes. CRP has the highest affinity for phosphocholine on bacteria or as a mixture of sphingomyelin and phosphatidylcholine in eukaryotic membranes. CRP can also recognize self ligands such as plasma lipoproteins, damaged cell membranes, several phospholipids, small nuclear ribonucleoprotein components, and apoptotic cells. CRP can also recognize self ligands such as plasma lipoproteins, damaged cell membranes, several phospholipids, small nuclear ribonucleoprotein components, and apoptotic cells. Some extrinsic ligands that CRP bind are glygan, phospholipids, capsular or cell body components of bacteria, fungi, and parasites, as well as plant particles. Some extrinsic ligands that CRP bind are glygan, phospholipids, capsular or cell body components of bacteria, fungi, and parasites, as well as plant particles.

CRP 10 – 40 mg/L suggest mild inflammation or Viral infection 10 – 40 mg/L suggest mild inflammation or Viral infection 40 – 200 mg/L acute inflammation or bacterial infection 40 – 200 mg/L acute inflammation or bacterial infection >300 mg/L extensive trauma, burns and severe bacterial infection >300 mg/L extensive trauma, burns and severe bacterial infection

CRP Why measure CRP ? Why measure CRP ? –On its own non-specific but very sensitive – works by binding to exposed DNA in damaged or dead cells – scavenger to clear damaged tissue from the circulation –needs to be interpreted with full clinical information to be useful –Can reflect the extent and activity of an injury/insult and response to treatment

CRP Causes of a raised CRP Infection Infection Most microbial infections (serial measurements are most useful) Most microbial infections (serial measurements are most useful) Chronic infection (lower than in acute infection) Chronic infection (lower than in acute infection)

CRP Uncomplicated virus infections (e.g. Viral meningitis) will give little or no rise whereas complex viruses (e.g. Herpes simplex) especially in immuno compromised patients may lead to major elevations in serum CRP Uncomplicated virus infections (e.g. Viral meningitis) will give little or no rise whereas complex viruses (e.g. Herpes simplex) especially in immuno compromised patients may lead to major elevations in serum CRP CRP changes occur in all ages and in all stages of health e.g. AIDS, Steroid therapy, irradiation and may be useful as other clinical signs and symptoms may be lacking or masked CRP changes occur in all ages and in all stages of health e.g. AIDS, Steroid therapy, irradiation and may be useful as other clinical signs and symptoms may be lacking or masked

CRP CRP may precede clinical signs of infection by up to hours CRP may precede clinical signs of infection by up to hours CRP levels can be used to monitor antibiotic therapy and further rises can indicate recurrence of infection CRP levels can be used to monitor antibiotic therapy and further rises can indicate recurrence of infection Bacterial meningitis will produce a much higher level of CRP than viral meningitis Bacterial meningitis will produce a much higher level of CRP than viral meningitis

CRP Causes of a raised CRP Inflammatory Disease Inflammatory Disease Chronic inflammatory disease associated with elevated CRP e.g. RA and monitoring serially reflects the extent and activity of the disease Chronic inflammatory disease associated with elevated CRP e.g. RA and monitoring serially reflects the extent and activity of the disease Persistent elevation of CRP in the absence of clinical signs and symptoms may indicate relapse of an underlying inflammation requiring additional treatment Persistent elevation of CRP in the absence of clinical signs and symptoms may indicate relapse of an underlying inflammation requiring additional treatment

CRP Causes of a raised CRP: Allograft rejection post transplant Allograft rejection post transplant post transplant monitoring can help prompt possible rejection (must exclude possibility of infection) post transplant monitoring can help prompt possible rejection (must exclude possibility of infection) return to normal followed by a rise can indicate rejection return to normal followed by a rise can indicate rejection consistent modest elevation may suggest chronic rejection that may require graftectomy consistent modest elevation may suggest chronic rejection that may require graftectomy

CRP Causes of a raised CRP Malignancy Malignancy Most malignant tumours cause APP response especially Hodgkins Lymphoma and Renal Carcinoma Most malignant tumours cause APP response especially Hodgkins Lymphoma and Renal Carcinoma Some anecdotal evidence suggests CRP levels correlate to prognosis in prostate and bladder carcinoma Some anecdotal evidence suggests CRP levels correlate to prognosis in prostate and bladder carcinoma

CRP Causes of a raised CRP Necrosis Necrosis any tissue necrosis causes a rise in CRP any tissue necrosis causes a rise in CRP MI will cause a rise in CRP as will any embolytic lesion MI will cause a rise in CRP as will any embolytic lesion Angina does not cause a raised CRP but pericarditis, PE and pleurisy do. Angina does not cause a raised CRP but pericarditis, PE and pleurisy do. CRP cam be used monitor pancreatitis CRP cam be used monitor pancreatitis

CRP Causes of a raised CR Trauma Trauma CRP rises after any significant trauma, surgery or burns peaking after 2 days. Any alteration in this pattern may suggest underlying infection CRP rises after any significant trauma, surgery or burns peaking after 2 days. Any alteration in this pattern may suggest underlying infection

CRP Causes of a raised CRP Other Other SLE (auto immune disease) SLE (auto immune disease) Leukaemia Leukaemia graft v host disease graft v host disease Ulcerative colitis Ulcerative colitis