Feline infectious peritonitis (FIP) is one of the most widespread feline infectious diseases worldwide and still represents a diagnostic ‘challenge’ for veterinarians. Definitive diagnosis is not straightforward ‘in vivo’ as both the classical clinico-pathological changes of the disease and the causative agent (coronavirus) must be demonstrated.

Among the acute phase proteins, alpha-1-glycoprotein acid (AGP) has historically been considered the most useful for the diagnosis of FIP, but in recent years, the method used for its measurement (radial immuno-diffusion) has no longer been available.

Finally, as of 2023, it will be possible in our laboratory to measure alpha-1-glycoprotein acid (AGP) in feline sera, using an ELISA method recently validated in the species.

Alpha-1-glycoprotein acid (AGP) is a positive acute phase protein (APP). Its concentration therefore increases during the inflammatory process. In cats, AGP can be measured by immunological methods (e.g. ELISA), but these require antibodies specific to the feline protein, as the use of antibodies developed in other species detects proteins other than feline AGP and therefore gives results that do not correspond to the true concentration of the molecule. For several years, it was not possible to accurately determine AGP because the radial immuno-diffusion kit, which was considered the only one capable of recognising feline AGP, was out of production. Recently, however, an ELISA test with adequate precision and accuracy has been developed for diagnostic use.

Among the acute phase proteins, AGP behaves in almost all species as a minor or moderate APP. Its increases, that is, are quantitatively limited: in the case of an inflammatory process, increases of 4-5 times normal concentrations are detected (in the blood of healthy individuals it is present in concentrations of less than 0.5 mg/mL in almost all species).

Even in cats, AGP shows moderate serum increases in most mild or non-specific inflammatory conditions. The exception is feline infectious peritonitis (FIP), in which increases in serum AGP concentration are often significant (3 to 10 times the normal concentration).

This makes AGP a very powerful diagnostic tool in the course of FIP, whether wet or dry, and makes it the marker of choice, among APPs, to differentiate this disease from other inflammatory or infectious conditions with similar symptomatology.

In fact, while the concentration of other inflammatory proteins, such as serum amyloid A (SAA) and haptoglobin (Hp), also increases during FIP, the increases in the latter are very unspecific: SAA in particular increases greatly (tens to hundreds of times the normal values) both during FIP and during other inflammatory diseases, and, in contrast, Hp shows modest-to-moderate increases both during FIP and during other diseases.

The above mentioned APPs therefore cannot be used to differentiate FIP from other diseases with similar presentation. Of course, even in the course of FIP one can occasionally observe modest increases in AGP, but it is still above normal values. In this case, it is important to correlate the increases in AGP with the symptomatic picture and with any other laboratory changes consistent with FIP, most notably serum protein electrophoresis, which in FIP shows peaks of alpha 2 and gamma globulins, and the cytochemical picture of the effusion (showing high protein, albumin/globulin ratio <1. 0, high LDH/TNCC ratio, and nonspecific inflammatory cytology characterised predominantly by nondegenerate neutrophils and a granular protein background), possibly associated with PCR-positive coronavirus, which, although it may be negative in about one-third of cats with FIP (PCR sensitivity on effusion about 70%), if positive confirms the diagnosis (PCR specificity on effusion close to 100%). The finding of AGP values within the reference ranges, on the other hand, tends to rule out FIP and induce one to look for other causes of any symptoms detected. Similarly, it is not useful to measure AGP in healthy cats that are serologically positive for coronavirus to try to predict the development of FIP. AGP is in fact an inflammatory marker, and even if the cat is seropositive, its serum concentration remains normal until the inflammation associated with coronavirus-induced disease develops. In other words, increases in AGP only occur after symptoms have appeared and not before. Finally, a recent study conducted in countries where nucleoside analogue therapy can be prescribed and administered to combat FIP showed that AGP tends to normalise earlier than other laboratory parameters in cats that respond to therapy, while it remains unchanged in cats in which treatment does not provide the desired results. Suspicion clinique et biologique de PIF

Ultimately, therefore, determination of AGP is recommended not only in any inflammatory process, in which it usually shows modest elevations in line with those of other FIPs, but especially when the symptoms detected lead to a clinical suspicion of dry or wet FIP: if the AGP values are within the reference ranges FIP can be ruled out, if, on the other hand, the values are modestly increased, FIP should be considered as possible if other clinical or laboratory changes support it, if the values are elevated AGP can be a diagnostic confirmatory tool and, when treatment with licensed antiviral drugs is possible, it can be considered the ideal marker for monitoring therapy and identifying ‘responders’.

Bibliography :

Addie DD et al (2022) Alpha-1 Acid Glycoprotein Reduction Differentiated Recovery from Remission in a Small Cohort of Cats Treated for Feline Infectious Peritonitis. Viruses. Apr 1;14(4): 744. doi: 10.3390/v14040744

Hazuchova K et al (2017) Usefulness of acute phase proteins in differentiating between feline infectious peritonitis and other diseases in cats with body cavity effusions. J Feline Med Surg. Aug;19(8):809-816. doi: 10.1177/1098612X16658925. Epub 2016 Jul 18.

Paltrinieri S et al (2007) Critical assessment of the diagnostic value of feline alpha1-acid glycoprotein for feline infectious peritonitis using the likelihood ratios approach. J Vet Diagn Invest. May;19(3): 266-72.

Saverio Paltrinieri, Vet. Doctor EBVS European Specialist in Veterinary Clinical Pathology (Dipl. ECVCP); Università di Milano
Walter Bertazzolo, Vet. Doctor EBVS European Specialist in Veterinary Clinical Pathology (Dipl. ECVCP); MYLAV Scientific Director