Review
Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine

https://doi.org/10.1016/j.tvjl.2010.04.009Get rights and content

Abstract

Acute phase proteins (APPs) have been used as biomarkers of inflammation, infection and trauma for decades in human medicine but have been relatively under-utilised in the context of veterinary medicine. However, significant progress has been made in the detection, measurement and application of APPs as biomarkers in both companion and farm animal medicine over recent years. In the dog, C-reactive protein, haptoglobin and serum amyloid A have been identified as significant diagnostic ‘markers’ of steroid-responsive meningitis-arteritis, while in cats and cattle haptoglobin and α1 acid glycoprotein and haptoglobin and serum amyloid A have proved valuable biomarkers of disease, respectively. In dairy cattle, haptoglobin and a mammary-associated serum amyloid A3 isoform, produced by the inflamed mammary gland during episodes of mastitis, have great potential as biomarkers of this economically important disease. Understanding the use of APP as biomarkers of inflammatory conditions of domestic animals has expanded significantly over recent years, and, with the insights provided by ongoing research, it is likely that these compounds will be increasingly used in the future in the diagnosis and prognosis of both companion and farm animal disease.

Introduction

The acute phase proteins (APPs) are blood proteins that can be used to assess the innate immune system’s systemic response to infection, inflammation or trauma (Murata et al., 2004, Petersen et al., 2004, Ceron et al., 2005). By definition, these proteins change their serum concentrations by >25% in response to pro-inflammatory cytokines stimulated during the disease process. As quantitative biomarkers of disease, APPs can be used in diagnosis, prognosis and in monitoring response to therapy, as well as in general health screening. These biomarkers are highly sensitive indicators of inflammation but lack specificity and there are major species differences in the APP response (Table 1).

In any given species, particular APPs demonstrate ‘major’, ‘moderate’ or ‘minor’ responses. A major APP ‘responder’ has a low serum concentration (<1 μg/L) in healthy animals that rises dramatically by 100–1000-fold on stimulation, peaking at 24–48 h and then declining rapidly during the recovery phase. Moderate responders increase some 5–10-fold on activation, peak after 2–3 days, and decrease more slowly than major APP ‘responders’. A minor APP responder gradually increases by between 50% and 100% of its resting level. ‘Negative’ APP biomarkers, which fall in concentration during the inflammatory response, have also been identified, although apart from albumin, their use in veterinary clinical pathology is not common. This short review focuses on features of the APP biomarkers currently in use in small companion animals and cattle. Similar biomarkers of inflammation and infection in species such as pigs and horses have been reviewed elsewhere (Petersen et al., 2004).

Section snippets

Acute phase proteins in canine medicine

C-reactive protein (CRP) is the major human APP and is one of the most frequently requested biochemical tests in medical laboratories. However, there is considerable species variation in the pathophysiology of CRP. In a number of species such as the dog, CRP is a major APP and its serum concentration can increase rapidly from <1 mg/L to >100 mg/L as part of a number of infectious diseases including babesiosis, leishmaniosis, leptospirosis, parvovirus infection and E. coli endotoxaemia (Table 2) (

Acute phase proteins in feline medicine

Although less research has been carried out on the feline than on the canine acute phase response, α1 acid glycoprotein (AGP) in feline serum and peritoneal fluid is a recognised biomarker of feline infectious peritonitis (Duthie et al., 1997, Giordano et al., 2004). Raised levels of AGP have also been reported in cats with neoplasia (Selting et al., 2000), including lymphoma (Correa et al., 2001), although this protein is not prognostic for survival. The SAA concentration may be a useful

Acute phase proteins in ruminant medicine

Ruminants are significantly different to other species in their acute phase response in that Hp is a major APP (Table 3). In healthy cattle the serum Hp concentration is <20 mg/L but can increase to >2 g/L within 2 days of infection. In cattle, Hp is effective in the diagnosis and prognosis of mastitis, enteritis, peritonitis, pneumonia, endocarditis, and endometritis (Murata et al., 2004, Petersen et al., 2004). Elevations in this protein have also been reported in cows with fatty liver syndrome,

Conclusions

A critical mass of knowledge in the use of APPs as biomarkers of inflammatory conditions of domestic animals, has accumulated over recent years, so that there is now sufficient understanding of the pathophysiology of the response to support the use of these compounds as diagnostic tools in clinical settings. With the insights provided by ongoing research in the area, it is likely that these analytes will be increasingly used in the diagnosis and prognosis of both companion and farm animal

Conflict of interest statement

PDE is a shareholder and consultant to Reactiv Lab Ltd, a veterinary diagnostic company with acute phase protein interests. No other author has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper.

Acknowledgements

Research in APP undertaken by the authors has been supported by BBSRC and EU funding and the many colleagues who have contributed to this research at The Acute Phase Laboratory of The Faculty of Veterinary Medicine, The University of Glasgow, UK, are thanked for their contributions.

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