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

BACKGROUND

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.

HYPOTHESIS/

OBJECTIVES

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.

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

METHODS

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.

RESULTS

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.

CONCLUSIONS AND CLINICAL

IMPORTANCE

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.