Feline infectious peritonitis diagnosis and prognosis: acute phase proteins and miRNA signatures

Feline Infectious Peritonitis (FIP) is a devastating viral disease in domestic and wild cats caused by feline coronavirus (FCoV) infection. This study aimed to monitor the concentrations of acute phase proteins (APPs): alpha-1-acid glycoprotein, serum amyloid A and haptoglobin (AGP, SAA, and Hp, respectively) in cats with FIP at diagnosis and during treatment with antiviral drugs GS-441524 and/or Remdesivir. Therapeutic drug monitoring (TDM) of these antiviral drugs was also performed to assess their potential relationship with APPs and to assess drug concentration. This study also serves as a preliminary investigation, to explore potential microRNA (miRNA) in cats diagnosed with FIP. Serum concentrations of AGP, SAA, and Hp were measured using spatial proximity analyte reagent capture luminescence. Samples for APP assessment and TDM were taken at diagnosis and several intervals during and post-treatment. For miRNA analysis, samples were subsequently collected from FIP-diagnosed cats before treatment and next-generation sequencing (NGS) was also utilised to attempt to begin to profile miRNA expression. Prior to treatment initiation, all cats exhibited elevated concentrations of AGP, SAA, and Hp, indicating systemic inflammation characteristic of FIP. Statistical analysis was employed to define cut-off values for each APP concentration, aiding in the diagnosis of FIP. Following treatment with GS-441524 and/or Remdesivir, a significant decrease in APP concentrations was observed during the treatment period. Notably, by week 4 of treatment, some cats demonstrated normalisation of APP concentrations, suggesting a positive response to therapy. None of the APPs were significantly affected by the dose of antiviral given or the concentration absorbed by each cat, although the duration of treatment and individual patients did significantly affect APPs. Therapeutic drug monitoring demonstrated a wide variability in the absorption of antiviral drugs, identifying 3 groups of cats according to plasma concentrations maintained: Low, Normal and High. The Low group consisted of a small subset of cats that failed to maintain adequate concentrations regardless of dose or dosing frequency. The miRNA analysis is ongoing and further investigation is continuing to achieve comprehensive results. However, several miRNAs have been found to be conserved within FIP, potentially differentiating these cases from other cats. It is hoped NGS analysis of miRNA profiles will reveal distinct expression patterns associated with FIP pathogenesis and treatment response. Individual miRNAs or miRNA profiles may serve as potential biomarkers for predicting treatment outcomes and understanding disease progression. In conclusion, our findings suggest that APPs are useful tools in diagnosing FIP and that monitoring AGP concentrations, in conjunction with TDM, holds promise in assessing treatment response and disease severity in cats diagnosed with FIP. Further investigations are warranted to validate these findings and optimise treatment strategies for this distressing disease.