The Importance of AGP in FIP Diagnosis: An Overview

Maigan Espinili Maruquin

  1. The Feline Infectious Peritonitis (FIP)

The coronaviruses are enveloped, positive-sense single-stranded RNA viruses with non-segmented genomes of around 30,000 nucleotides in length (Tasker 2018)( Siddell SG, 1995). The feline coronavirus (FCoV) has two pathotypes distinguished by their biological behavior. The highly prevalent feline enteric coronavirus (FECV) is highly contagious with transmission from faeces of shedding cats (Felten and Hartmann 2019). However, most cases are asymptomatic or displays mild gastrointestinal clinical signs, (Addie, Toth et al. 1995, Pedersen, Sato et al. 2004, Pedersen, Allen et al. 2008, Pedersen 2009, Vogel, Van der Lubben et al. 2010, Tasker 2018, Felten and Hartmann 2019). On the other hand, the feline infectious peritonitis virus (FIPV) is a mutation within a small percentage of infected cats and it results to a fatal disease feline infectious peritonitis (FIP), commonly in young cats (Pedersen, Boyle et al. 1981, Pedersen, Boyle et al. 1981, Addie, Toth et al. 1995, Vennema, Poland et al. 1998, Pedersen 2009, Tasker 2018, Felten and Hartmann 2019). However, the exact gene causing mutation is still unknown (Felten and Hartmann 2019).

The FIP may appear in two clinically distinct forms: the wet form and dry form, which is effusive and granulomatous forms, respectively (Wolfe and Griesemer 1966, Montali and Strandberg 1972, Pedersen 2009, Hazuchova, Held et al. 2016). The development of FIP is affected by three factors.  First is the viral factor wherein studies relative to mutation of the FCoV S gene where presented (Tasker 2018) and the replication in monocytes, and activation of infected monocytes were also considered important in the development of FIP (Kipar and Meli 2014, Tasker 2018). Second factor considered is the host’s immune response, breed and genetic (de Groot-Mijnes, van Dun et al. 2005, Dewerchin, Cornelissen et al. 2005, Golovko, Lyons et al. 2013, Pedersen, Liu et al. 2016, Tasker 2018). Finally, another factor affecting the FIP development is the environment- level of stress and overcrowding (Tasker 2018).

Fig. 01. Manifestation of moderate abdominal distention due to peritoneal effusion. A clinical sign of wet (effusive) FIP.

Common clinical signs for the FIP infected cats include lethargy, anorexia, weight loss, fluctuating pyrexia, and sometimes presents jaundice (Tasker 2018). On the other hand, wet FIP cases can be associated with abdominal, pleural and/ or pericardial effusions, and progresses within few days to weeks with severe limiting survival (Ritz, Egberink et al. 2007, Tasker 2018). Whereas, dry FIP usually displays neurological signs (Crawford, Stoll et al. 2017) or ocular signs, which progresses in a few weeks to months and are more chronic (Tasker 2018).

  1. The alpha- 1 acid glycoprotein (AGP) in FIP diagnosis

Prior to acquired immune response, part of the innate response is the acute phase response (Murata, Shimada et al. 2004, Schmidt and Eckersall 2015). Proteins known as the acute phase proteins (APPs) are then increased in production from hepatocytes and peripheral tissues and then released (Schmidt and Eckersall 2015). These blood proteins can be used to evaluate the innate response to infection, inflammation or trauma (Murata, Shimada et al. 2004, Petersen, Nielsen et al. 2004, Ceron, Eckersall et al. 2005, Eckersall and Bell 2010). With changes by >25% in the serum concentration in response to disease stimulation, APPs are considered useful quantitative biomarkers of diseases- in diagnosis, prognosis, response to therapy, and in general health screening (Eckersall and Bell 2010).

In response to inflammations, the serum alpha- 1 acid glycoprotein (AGP) concentration increases as a major acute phase protein in cats (Ceron, Eckersall et al. 2005, Paltrinieri 2008, Giori, Giordano et al. 2011). Studies showed increased serum AGP concentration in cats infected with FIP (Duthie, Eckersall et al. 1997, Giordano, Spagnolo et al. 2004, Giori, Giordano et al. 2011).

The feline AGP in both serum and peritoneal fluid are known biomarker for FIP (Duthie, Eckersall et al. 1997, Giordano, Spagnolo et al. 2004, Eckersall and Bell 2010). In a study conducted, AGP in effusion showed to be the best APP to distinguish between cats with and without FIP (Hazuchova, Held et al. 2016). Although AGP elevations are not specific for FIP, the measurement is helpful in the diagnosis of FIP, and levels >1.5 mg/ml are often observed in FIP cases (Tasker 2018). It was then concluded that the higher levels increase the index of suspicion (Duthie, Eckersall et al. 1997, Paltrinieri, Giordano et al. 2007, Giori, Giordano et al. 2011, Hazuchova, Held et al. 2016, Tasker 2018).

With difficulty in diagnosing FIP through conventional approaches (Addie, Paltrinieri et al. 2004, Paltrinieri 2008), samples from FIP infected cats showed AGP seemed to be associated with viral antigen and are seen present in large amounts (Paltrinieri, Giordano et al. 2004, Paltrinieri 2008). Nevertheless, AGP plays role in drug-binding, as an immunomodulatory agent, and acts as a plasma transport protein (Ceron, Eckersall et al. 2005, Ceciliani, Ceron et al. 2012, Schmidt and Eckersall 2015).




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