Introduction

• The acute phase response (APR) is a non-specific inflammatory reaction that develops shortly after tissue damage (infection, immunological, neoplasia, trauma, and parasitic conditions). Despite its name, the acute phase response accompanies both acute and chronic inflammatory states.
• The acute-phase response includes changes in concentration of plasma proteins called acute phase proteins (APPs). APPs can be divided into two groups:
  • Positive APPs (glycoproteins synthesized and released predominantly by hepatocytes in response to pro-inflammatory cytokines) and
  • Negative APPs (proteins whose concentration reduces in acute inflammation usually due to reduced hepatocyte synthesis).
• Most animals have the same acute phase proteins, although the magnitude of response varies between species.
• The positive APPs in dogs and cats can be further classified by the magnitude of the increase in their plasma concentration in response to stimuli into major APPs (10-100 fold increase), and moderate APPs (2-10 fold increase).
• In dogs, C-reactive protein (CRP) and serum amyloid A (SAA) are major APPs, haptoglobin (Hp) and alpha 1-acid glycoprotein (AGP) are moderate APPs.
• Extremely sensitive but non-specific markers of inflammation. An increase in circulating concentrations of APPs is 6-14 times more sensitive a marker of inflammation than an increase in leukocyte count.
• All APPs are measured in serum samples.
• APP concentrations vary in puppies, pregnant bitches and certain breeds (including Greyhounds and Miniature Schnauzers), but this physiological influence is likely to be minor and clinically insignificant.

Acute phase proteins as a diagnostic test

Indications for CRP measurement

Examples of the use of APPs in clinical practice

Diagnosis of pyometra, neoplasia and leishmaniasis

Treatment monitoring

Further Reading

Publications

Refereed papers

• Recent references from PubMed and VetMedResource.
• Alexandrakis L, Tuli R, Ractliffe S C et al (2014) Utility of a multiple serum biomarker test to monitor remission status and relapse in dogs with lymphoma undergoing treatment with chemotherapy. Vet Comp Oncol 15 (1), 6-17 PubMed.
• Lowrie M, Penderis J, McLaughlin M et al (2009) Steroid responsive meningitis-arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006-2008). JVIM 23, 862-870 PubMed.
• Lowrie M, Penderis J, Eckersall P D et al (2009) The role of acute phase proteins in diagnosis and management of steroid-responsive meningitis arteritis in dogs. Vet J 182 (1), 125-130 PubMed.
• Parra M D, Papasouliotis K & Cerón J J (2006) Concentrations of C-reactive protein in effusions in dogs. Vet Rec 158 (22), 753-757 PubMed.
• Rush J E, Lee N D, Freeman L M et al (2006) C-reactive protein concentration in dogs with chronic valvular disease. J Vet Intern Med 20 (3), 635-69 PubMed.
• Ceron J J, Eckersall P D & Martýnez-Subiela S (2005) Acute phase proteins in dogs and cats: current knowledge and future perspectives. Vet Clin Pathol 34 (2), 85-99 PubMed.
• Hurter K, Spreng D, Rytz U et al (2005) Measurements of C-reactive protein in serum and lactate dehydrogenase in serum and synovial fluid of patients with osteoarthritis. Vet J 169 (2), 281-285 PubMed.
• Parra M D, Tecles F, Martínez-Subiela S et al (2005) C-reactive protein measurement in canine saliva. J Vet Diagn Invest 17 (2), 139-144 PubMed.
• Parra M D, Tuomola M, Cabezas-Herrera J et al (2005) Use of a time-resolved immunofluorometric assay for determination of canine C-reactive protein concentrations in whole blood. Am J Vet Res 66 (1), 62-66 PubMed.
• Fransson B A, Karlstam E, Bergstrom A et al (2004) C-reactive Protein in the Differentiation of Pyometra From Cystic Endometrial Hyperplasia/Mucometra in Dogs. JAAHA 40 (5), 391-399 PubMed.
• Martínez-Subiela S, Ginel P J, Cerón J J (2004) Effects of different glucocorticoid treatments on serum acute phase proteins in dogs. Vet Rec 154 (26), 814-817 PubMed.
• McGrotty Y L, Knottenbelt C M, Ramsey I K et al (2004) Evaluation of a rapid assay for canine C-reactive protein. Vet Rec 154 (6), 175-176 PubMed.
• Jergens A E, Schreiner C A, Frank D E et al (2003) A scoring index for disease activity in canine inflammatory bowel disease. JVIM 17 (3), 291-297 PubMed.
• Kjelgaard-Hansen M, Jensen A L, Kristensen A T (2003) Evaluation of a commercially available human C-reactive protein (CRP) turbidometric immunoassay for determination of canine serum CRP concentration. Vet Clin Path 32 (2), 81-87 PubMed.
• Martínez-Subiela S, Tecles F, Eckersall P D et al (2002) Serum concentrations of acute phase proteins in dogs with leishmaniasis. Vet Rec 150 (8), 241-244 PubMed.
• Thougaard V, Hellmén E, Pedersen H D et al (1999) Correlation between 1-Acid Glycoprotein and Total Sialic Acid in Serum from Dogs with Tumours. Zentralbl Veterinarmed A 46 (4), 231-237 PubMed.
• Burton S A, Honor D J, Mackenzie A L et al (1994) C-reactive protein concentration in dogs with inflammatory leukograms. Am J Vet Res 55 (5), 613-618 PubMed.

Other sources of information

• Bell R, Eckersall D (2008) Laboratory updates: Acute phase protein tests for diagnosis and monitoring of disease in small animals. UK Vet 13, 1-4.
• Tecles F, Martínez Subiela S, Parra M D, Spiranelli E, Paltrinieri S, Cerón J J (2004) Use of Acute Phase Proteins for Monitoring Treatment Evolution in Dogs with Different Pathologic Conditions. 14th ECVIM-CA Congress.
• Holm J L,Rozanski E A, Freeman L M, Webster C R L (2003) C-Reactive Protein Concentrations in Canine Acute Pancreatitis. International Veterinary Emergency and Critical Care Symposium 2003. (Abstract)
• Tecles F, Parra M D, Cerón J J (2003) Use of C-Reactive Protein Measurement in Saliva as a Marker of Inflammation in Dogs. 13th ECVIM-CA Congress 2003 (Abstract).
• Martínez-Subiela S, Cerón J J (2002) Serum amyloid A levels in canine leishmaniasis. European Society of Veterinary Clinical Pathology (ESVCP) 4th Annual MeetingIn conjunction with the European College of Veterinary Internal Medicine (ECVIM) 12th Annual Meeting.
• European Concerted Action on Animal Acute Phase Proteins.