Positive Acute Phase Reactants
Positive acute phase reactants are proteins whose plasma concentrations increase by at least 25% during inflammation, with the major ones being C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, alpha-1 acid glycoprotein, haptoglobin, ceruloplasmin, alpha-1 protease inhibitor, and alpha-1 antichymotrypsin. 1, 2, 3
Major Positive Acute Phase Reactants
Proteins with Dramatic Increases (up to 1000-fold)
C-reactive protein (CRP) can increase up to 1000-fold during acute inflammation and is the most clinically useful biomarker due to its rapid rise within 12-24 hours, peaking at 48 hours, superior standardization, and stability in serum or plasma at room temperature or frozen for extended periods 1, 2
Serum amyloid A (SAA) may also increase up to 1000-fold during inflammation and serves as a precursor to protein AA in secondary amyloidosis 1, 2
Proteins with Moderate Increases (2-4 fold)
Alpha-1 acid glycoprotein (α1-AG) increases approximately 2-4 fold and may be more specific than CRP for detecting inflammation in maintenance dialysis patients 1, 2, 3
Fibrinogen increases approximately 2-4 fold during inflammation and plays roles beyond clot formation, including binding to complement receptor type 3 1, 2, 3
Additional Positive Acute Phase Reactants
Haptoglobin increases during inflammation and functions to bind free hemoglobin, neutralizing toxic molecules 2, 3
Ceruloplasmin rises during inflammatory states and is involved in copper transport and oxidative stress responses 1, 2, 3
Alpha-1 protease inhibitor (alpha-1 antitrypsin) increases during inflammation and provides protease inhibition 2, 3
Alpha-1 antichymotrypsin increases during acute phase response and contributes to protease regulation 2, 3
Ferritin increases during inflammation and is elevated in conditions such as rheumatoid arthritis, adult-onset Still's disease, and active systemic lupus erythematosus 1, 4
Regulatory Mechanisms
Interleukin-6 (IL-6) is the principal regulator of most acute phase protein genes and is recognized as having multiple functional capabilities in inducing the acute phase response 2, 3
IL-1 and tumor necrosis factor-alpha (TNF-α) also regulate acute phase gene expression, with IL-1 and TNF-α mediated stimulation being synergistically enhanced by IL-6 type cytokines 5, 2, 3
All major positive acute phase proteins are synthesized mainly in the liver, though each may be produced at extrahepatic sites as well 2, 3
Clinical Significance
Positive acute phase proteins are elevated in all infective conditions, trauma, burns, tissue infarction, inflammatory conditions, and advanced malignancy 4, 2
The acute phase response occurs approximately 90 minutes after the onset of a systemic inflammatory reaction 6
Serial monitoring of positive acute phase proteins (particularly CRP and α1-AG) during episodes of inflammation follows patterns similar to those found in acutely ill individuals 1
Serum albumin concentrations are inversely correlated with serum levels of positive acute phase proteins, making albumin a negative acute phase reactant 1