Protein S is Not an Acute Phase Protein
Among the options given, Protein S is not an acute phase protein, while Fibrinogen, Haptoglobin, and Alpha-1 Antitrypsin are all classified as positive acute phase proteins.
Understanding Acute Phase Proteins
Acute phase proteins are a class of proteins whose plasma concentrations change in response to inflammation. They are primarily synthesized by the liver in response to inflammatory cytokines such as IL-1, IL-6, and TNF-α 1.
Positive Acute Phase Proteins
These proteins increase in concentration during inflammation:
Fibrinogen: A well-established acute phase reactant that serves as a clotting factor. It increases approximately 2-4 fold during inflammatory states 2. It's specifically identified as an acute phase protein in multiple guidelines 1.
Haptoglobin: A positive acute phase protein that binds free hemoglobin, preventing oxidative damage. It's explicitly listed as an acute phase protein in the literature 1, 3.
Alpha-1 Antitrypsin: A protease inhibitor that increases during inflammation to protect tissues from enzymatic damage. It's classified as a positive acute phase protein in multiple sources 1, 3.
Protein S: Not an Acute Phase Protein
Protein S is fundamentally different from the other options:
It functions as an anticoagulant protein that works with activated Protein C to inactivate factors Va and VIIIa 4.
Unlike acute phase proteins, Protein S levels actually decrease during inflammatory states, not because it's a negative acute phase protein, but because inflammation increases levels of C4b-binding protein (C4bBP), which binds to Protein S and reduces its free active form 4.
Protein S is not listed among acute phase proteins in any of the guidelines or comprehensive reviews of acute phase proteins 1, 3, 2.
Clinical Significance
Understanding which proteins are acute phase reactants is important for:
Diagnostic purposes: Acute phase proteins like CRP, fibrinogen, and haptoglobin are used to detect and monitor inflammatory conditions.
Disease monitoring: Changes in acute phase protein levels can indicate disease progression or response to treatment.
Interpreting laboratory results: During inflammation, increases in acute phase proteins (like fibrinogen, haptoglobin, and alpha-1 antitrypsin) are expected, while changes in Protein S would be due to different mechanisms.
Common Acute Phase Proteins
The American Heart Association and CDC have identified several established acute phase proteins 1:
- C-reactive protein (CRP)
- Serum Amyloid A (SAA)
- Fibrinogen
- Haptoglobin
- Alpha-1 acid glycoprotein
- Alpha-1 antitrypsin
- Ceruloplasmin
Protein S is notably absent from these comprehensive lists of acute phase proteins.
In conclusion, while Fibrinogen, Haptoglobin, and Alpha-1 Antitrypsin are all positive acute phase proteins that increase during inflammation, Protein S is not classified as an acute phase protein and instead has anticoagulant functions that are actually impaired during inflammatory states.