Serum peptidomic profiling identifies systemic JAK-STAT and PI3K-Akt pathway dysregulation in cats with chronic...

Chronic gingivostomatitis in cats is a debilitating inflammatory disease marked by severe oral pain and systemic immune dysregulation. Although localized oral pathology is well-documented, the systemic peptidomic profile remains largely unclear.

Characterize the serum peptidomic profiles of cats with feline chronic gingivostomatitis (FCGS) and identify systemic biomarkers and signaling hubs that drive disease pathogenesis and therapeutic interactions.

Client-owned cats with clinically and histopathologically confirmed FCGS (n = 34) and healthy controls (n = 18).

A case-control, cross-sectional study was conducted. All cats were screened for feline leukemia virus, feline immunodeficiency virus, and feline heartworm infections. Serum samples were analyzed using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) to produce peptide mass fingerprints. Detailed peptide identification was conducted using nanoscale liquid chromatography-tandem mass spectrometry (nano LC-MS/MS). Functional enrichment and protein-protein/chemical interaction networks were developed using ShinyGO and the Kyoto Encyclopedia of Genes and Genomes database.

Both MALDI-TOF MS and nano LC-MS/MS identified distinct systemic protein signatures that distinguished FCGS from controls. Fifteen proteins showed significant changes, with 13 increased (including inflammatory markers such as interleukin (IL)-6 and interferon-γ) and 2 decreased (gastrin, IL-18). Network analysis identified 8 key proteins (eg, p21(CDKN1A), CASP1, IL-6) that interact with FCGS drug treatments. These systemic changes focus on the Janus kinase-signal transducers and activators of transcription (JAK-STAT) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT; PI3K-Akt) pathways, which are important therapeutic targets.

Our study provides a molecular framework for FCGS. Whereas MALDI-TOF MS enables rapid systemic profiling, nano LC-MS/MS identifies key dysregulated pathways, specifically IL-6/JAK-STAT and PI3K-Akt. These findings offer potential therapeutic targets and a basis for monitoring molecular pathology in affected cats.