Serum proteomic analysis identifies ITIH4 as potential novel biomarkers for feline infectious peritonitis

Feline infectious peritonitis (FIP) is a fatal feline disease. At present, the reference standard for FIP diagnosis is immunohistochemistry (IHC) of organs, but this method involves high time-related costs, invasive sampling procedures and professional requirements. Serological detection is a common auxiliary method for diagnosing diseases. As a result, we assessed the changes in the serum proteome of FIP patients with the aim of identifying novel specific serum biomarkers that could aid in the clinical diagnosis of FIP. Pre- and postinfection groups were compared and 92 differentially expressed proteins (DEPs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEPs revealed that the enriched GO terms and KEGG pathways among the DEPs were immune activation, peptidase regulator activity and the complement and coagulation cascade pathways. The level of peptidase regulator interalpha-trypsin inhibitor heavy chain 4 (ITIH4) in cat serum was significantly correlated with FIP. The areas under the ROC curve (AUCs) of full-length ITIH4 (f-ITIH4) and cleaved ITIH4 (c-ITIH4) expression were 0.922 and 1.000, respectively, which allowed the discrimination of FIP cats from healthy cats. These results suggest that ITIH4 may be a potential serum biomarker for detecting early FIP. SIGNIFICANCE: FIP causes fatal disease in cats of almost all ages, and there is currently no effective vaccine or treatment for FIP. Therefore, early diagnosis is extremely important for disease prevention and control. The results of the model and clinical samples revealed that ITIH4 was significantly increased in the serum of FIP cats. This study is the first to propose ITIH4 as a diagnostic biomarker in cats with FIP and our results suggest that serum ITIH4 levels might identify cats with FIP during the early stage.