Acute Phase Proteins



Clinically unremarkable but still ill?


Dr. Stefanie Klenner-Gastreich, Dipl. ECVCP, scil animal care company GmbH


Since the discovery of C-reactive protein (CRP) in the 1930s, the analysis of acutephase proteins (APP) has been established in human medicine for decades and is a routine in virtually every medical practice. However, this is still an exception in veterinary medicine [1,2]. A large number of scientific publications confirm the broad application potential and the diagnostic knowledge gained by the acute phase proteins also for the veterinarian [1,2,3].

Acute phase proteins not only provide a much more sensitive detection of systemic inflammatory responses than can be ensured by the clinical findings, leukocyte count and differential counts, but also allow a better assessment of the therapy outcome and prognosis [1].

The use of the acute phase proteins in practice has long been limited due to the lack of commercially available test systems. However, even though the veterinary physician has already provided automated in-house analytical methods for several years [1], this diagnostic potential is only used in isolated cases, depending on the geographic region you are located [2]. The question arises: why do veterinarians still relinquish these valuable parameters?

Acute-phase reaction

The acute phase reaction is a very early reaction of the organism, which still occurs before the stimulation of more specific immune reactions and thus in many cases before the onset of clear clinical symptoms. Acute phase proteins thus represent very sensitive markers for systemic inflammatory processes [3, 4].

Acute-phase proteins react differently in different animal species [3] (Table 1). The most significant APP are divided into major and moderate APP. Major APP (eg, CRP in the dog, serum amyloid A (SAA) in the cat and the horse) increase by 10 to 100 fold (rarely up to 1000 fold) within 24-48h after stimulation, while moderate APP react more slowly and increase less dramatically (5- to 10-fold increase within 2-3 days). Given the cytokines released by monocytes (IL- 1, IL-6 and TNF-α), the synthesis of the positive APP is predominantly performed in the liver. In addition to bacterial toxins and ischemic, infectious or neoplastic tissue damage, causative agents of cytokine release in the monocytes can basically be trauma of any type [3, 4].

Acute-phase proteins as screening parameters, especially in subclinical processes Because the synthesis of APP is triggered by a variety of different diseases, they are not specific for a specific disease [3]. Major APP, however, can be a much more sensitive parameter for systemic inflammatory responses than it is generally the case for body temperature or leukocyte count, [3] because of their rapid and distinct concentration increase and short half-life. The APP therefore provide valuable additional information in case of unspecific or missing clinical symptoms [4]. With their help, systemic inflammatory reactions due to infection, neoplasia, etc. can be identified very quickly. Table 2 and 3 show some of the diseases in which a rise in acute phase proteins has already been described [1,4].

The possibility to detect subclinical inflammatory reactions by means of the APP is of particular interest not only for small animal medicine but also offers completely new options for stock management and herd management [1, 3, 4]. Acute-phase proteins as a valuable parameter for therapy control and prognosis.

An increase in APP can in principle be found in both acute and chronic inflammatory processes [3]. The extent and duration of the concentration increase are directly related to the severity of the inflammatory process. Therefore, follow-up examinations of the APP are suitable both as prognostic parameters and for the assessment of the therapeutic outcome, which is one of the most interesting aspects[1, 3, 4]. Treatment of systemic inflammation is confirmed by a fall of the major APP within 1-2 days [1].

Perspectives

As a pioneer in the research of acute-phase proteins postulated in 2004, the time is ripe for the routine use of the acute-phase proteins.

“However, the analysis of the acute phase proteins will continue to be the most important parameter for the health of our pets in the future, (...) where any positive result require further investigation to determine the cause. A diagnostic regime which does not take in mind results of the acute phase reaction can only be described as suboptimal in the future "[6].

Take Home Message

The acute-phase reaction is the first immunological defense of the body for a variety of disorders such as trauma, infection, inflammation or neoplasia. The extent and duration of the concentration increase are directly related to the severity of the inflammatory process. Therefore, the APP are suitable both as a prognostic parameter and, in particular, for evaluating the therapy outcome.

References:

[1] Cray, C. et al. (2009): Acute phase response in animals: a review. Comparative Medicine 59, 517-526
[2] Eckersall, P.D. & Bell, R. (2010): Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine. The Veterinary Journal 185, 23-27
[3] Cerón, J. J. et al. (2005): Acute phase proteins in dogs and cats: current knowledge and future perspectives. Veterinary Clinical Pathology 34, 85-99
[4] Petersen, H.H. et al. (2004): Application of acute phase protein measurements in veterinary clinical chemistry. Veterinary Research 35, 163-187
[5] Murata, H. et al. (2004): Current research on acute phase proteins in veterinary diagnosis: an overview. The Veterinary Journal 168, 28-40
[6] Eckersall, P.D. (2004): The time is right for acute phase protein assays. Vet. J. 168, 3-5