Serum protein alterations characterize feline chronic gingivostomatitis: a case-control study of electrophoresis, immunoglobulin, and cytokine profiles

Objective: To characterize systemic immune alterations in feline chronic gingivostomatitis (FCGS) through serum protein electrophoresis (SPE), immunoglobulin (Ig), and cytokine profiling. We hypothesized that FCGS cases would exhibit polyclonal hyperglobulinemia, elevated Igs, and proinflammatory cytokine elevations compared to controls. Methods: Cats with FCGS and controls were prospectively enrolled in an observational case-control study at 2 veterinary dental practices. Exclusion criteria included FIV/FeLV infection, recent vaccination, corticosteroid administration, and systemic disease. A single preanesthetic serum sample was analyzed for 31 biomarkers, including SPE fractions, Ig concentrations, and cytokine levels. Results: 13 FCGS cats and 14 controls were enrolled. Six biomarkers differed significantly after false discovery rate (FDR) correction, with very large effect sizes (Hedges g = 1.43 to 2.27): globulin, IgG, γ globulin, total protein, albumin, and albumin-to-globulin ratio. Polyclonal gammopathy was present in 76.9% of FCGS cases. Seven cytokines showed medium to large effect sizes (Hedges g = 0.57 to 0.88) without surviving FDR correction. Hierarchical clustering separated 85% of cases from 79% of controls based on coordinated cytokine profiles despite modest individual elevations. Conclusions: This study confirms FCGS as a disease with a quantifiable, systemic inflammatory response characterized by polyclonal hypergammaglobulinemia and mixed T helper 1/2 cytokine activation. Clinical Relevance: FCGS extends beyond localized oral inflammation to involve measurable systemic immune dysregulation. Hyperglobulinemia, combined with oromucosal inflammation, should prompt diagnostic consideration of FCGS in cats. The coordinated activation of IL-8, IL-4, IFN-γ, and IL-6 identifies potential therapeutic targets for immunomodulatory intervention in refractory cases.