WHAT ARE ACUTE PHASE PROTEINS (APPs)?
APPs are blood proteins primarily produced by hepatocytes in the liver. 1 They are generated as part of the acute phase response, which serves to re-establish homeostasis and promote healing. 1,2 APPs respond to various stimuli like trauma, infection, or inflammation. 2 When used correctly, they can serve as valuable biomarkers of disease and provide crucial clinical insights.3
DIFFERENT TYPES OF ACUTE PHASE PROTEIN RESPONSE
APPs that increase in response to tissue injury are defined as positive, while those that decrease are defined as negative.3 The majority of APPs can be further categorised into three groups: major, moderate, and minor, based on the magnitude of their response to stimuli.3
DIFFERENT TYPES OF ACUTE PHASE PROTEIN RESPONSE
APPs that increase in response to tissue injury can be defined as positive, and those which decrease, defined as negative.3 The majority of APPs are positive and can be further split into three broad categories: major, moderate and minor, depending on the magnitude of their response to stimuli.3
In dogs, C-reactive protein (CRP) is an example of a major APP, whilst in cats, a major APP is alpha-1-acid glycoprotein (AGP).1 Both of these major APPs are available from Nextmune Laboratories UK.
| CHANGE FROM RESTING SERUM LEVEL | PEAK RESPONSE AFTER STIMULI | RETURN TO NORMAL | |
| Major
APPs |
10 – 100 x ↑ | 24 – 48 hours | Rapid |
| Moderate
APPs |
2 – 10 x ↑ | 48 – 72 hours | Slower than major APPs |
| Minor
APPs |
1.5 – 2x ↑ | Gradual | Gradual |
| Negative
APPs |
Variable ↓ | Variable | Variable |
Minor APPs are not commonly measured because, as the name suggests, the magnitude of change for these APPs is relatively small; this makes it more challenging to differentiate between clinically significant levels and those within the range of normal limits.3
Regardless of the category, while the stimulus persists, the APP level will remain changed; for positive APPs this means elevated. After the stimulus is removed, the APP level will return to within normal limits.3 The speed of the return varies between the APP categories and is another point of differentiation between them. The table1,2 to the left and the graph3 above provide some further insight:
Minor APPs are not commonly measured because, as the name suggests, the magnitude of change for these APPs is relatively small; this makes it more challenging to differentiate between clinically significant levels and those within the range of normal limits.3
Regardless of the category, while the stimulus persists, the APP level will remain changed; for positive APPs this means elevated. After the stimulus is removed, the APP level will return to within normal limits.3 The speed of the return varies between the APP categories and is another point of differentiation between them. The table1,2 and graph3 below provide some further insight:
| CHANGE FROM RESTING SERUM LEVEL | PEAK RESPONSE AFTER STIMULI | RETURN TO NORMAL | |
| Major
APPs |
10 – 100 x ↑ | 24 – 48 hours | Rapid |
| Moderate
APPs |
2 – 10 x ↑ | 48 – 72 hours | Slower than major APPs |
| Minor
APPs |
1.5 – 2x ↑ | Gradual | Gradual |
| Negative
APPs |
Variable ↓ | Variable | Variable |
CLINICAL USE OF ACUTE PHASE PROTEINS
Acute phase proteins have several clinical uses:
| Early indicator of inflammation | Due to their high sensitivity, APPs can serve as early indicators of inflammation, even at a sub-clinical stage.3 They offer a more stable, responsive, and accurate biomarker for detecting inflammation compared to measuring haematology alone.3 This is useful for pre-operative wellness testing and other clinical indications.2 |
|---|---|
| Supporting Diagnosis | APPs can aid in differential diagnoses. For example, alpha-1-acid glycoprotein (AGP) is helpful in differentiating feline infectious peritonitis (FIP) from other diseases, while APPs like CRP support the diagnosis of steroid-responsive meningitis-arteritis (SRMA).4,5 |
| Post-Surgery Monitoring | APP levels increase after surgical procedures in response to tissue trauma. A failure to decline or an unexpected decline followed by an increase can indicate complications like post-operative infections. Monitoring APPs, including CRP, has enabled the early detection of such issues.6 |
| Post-Treatment Monitoring | Sequential APP measurements help determine the success of treatment. Expectedly, a continual decline in APP levels towards the normal range is observed when treatment is effective. Failure to decline suggests a lack of treatment response, concurrent disease, or disease development.7 |
| Disease Surveillance | APPs, including CRP, are valuable for monitoring disease progression and early detection of relapse. They play a critical role in monitoring treatment response and identifying relapse in various diseases, such as SRMA.5 |
References
- Cray C, Zaias J & Altman NH (2009). Acute phase response in animals: a review. Comparative medicine; 59(6): 517–526.
- Eckersall PD & Bell R (2010). Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine. The Veterinary Journal; 185(1): 23-7.
- Bell R & Wilson C (2014). Acute phase proteins: how they are useful for practitioners. Veterinary Times.
- Hazuchova K, Held S, Neiger R (2017). Usefulness of acute phase proteins in differentiating between feline infectious peritonitis and other diseases in cats with body cavity effusions. Journal of Feline Medicine and Surgery; 19(8): 809-816.
- Lowrie M, Penderis J, Eckersall PD, McLaughlin M, Mellor D, Anderson TJ (2009). The role of acute phase proteins in diagnosis and management of steroid-responsive meningitis arteritis in dogs. The Veterinary Journal; 182(1): 125-30.
- Dabrowski R, Kostro K, Lisiecka U, Szczubiał M, Krakowski L (2009). Usefulness of C-reactive protein, serum amyloid A component, and haptoglobin determinations in bitches with pyometra for monitoring early post-ovariohysterectomy complications. Theriogenology; 1;72(4): 471-6.
- Seo KW, Lee JB, Ahn JO, Lee HW, Hwang CY, Youn HY, Lee CW (2012). C-reactive protein as an indicator of inflammatory responses to experimentally induced cystitis in dogs. J Vet Sci; 13(2): 179-85.