State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
J Proteomics. 2025 Jan 6;310:105338. doi: 10.1016/j.jprot.2024.105338. Epub 2024 Oct 23.
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.
猫传染性腹膜炎（Feline Infectious Peritonitis，FIP）是一种致命的猫科疾病。目前，FIP 的诊断参考标准是器官的免疫组织化学（Immunohistochemistry，IHC），但这种方法涉及高时间相关成本、有创采样程序和专业要求。血清学检测是诊断疾病的常用辅助方法。因此，我们评估了 FIP 患者血清蛋白质组的变化，旨在确定新的特异性血清生物标志物，以辅助 FIP 的临床诊断。比较了感染前后组，鉴定出 92 个差异表达蛋白（Differentially Expressed Proteins，DEPs）。对 DEPs 的基因本体论（Gene Ontology，GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析表明，DEPs 中富集的 GO 术语和 KEGG 通路包括免疫激活、肽酶调节活性和补体与凝血级联通路。猫血清中肽酶调节物内α-胰蛋白酶抑制剂重链 4（Inter-alpha-Trypsin Inhibitor Heavy Chain 4，ITIH4）的水平与 FIP 显著相关。全长 ITIH4（f-ITIH4）和切割 ITIH4（c-ITIH4）表达的 ROC 曲线下面积（Area Under the ROC Curve，AUC）分别为 0.922 和 1.000，能够区分 FIP 猫和健康猫。这些结果表明，ITIH4 可能是一种潜在的血清生物标志物，用于检测早期 FIP。意义：FIP 几乎会导致所有年龄段的猫致命疾病，目前尚无针对 FIP 的有效疫苗或治疗方法。因此，早期诊断对于疾病的预防和控制极为重要。模型和临床样本的结果表明，FIP 猫的血清中 ITIH4 显著增加。本研究首次提出 ITIH4 是 FIP 猫的诊断生物标志物，我们的结果表明，血清 ITIH4 水平可能在早期识别 FIP 猫。
