Histological, Immunological, and Genetic Analysis of Feline Chronic Gingivostomatitis

Abstract

Feline chronic gingivostomatitis (FCGS) is an immune-mediated inflammatory condition affecting the oral mucosa that results in substantial pain and suffering. The goal of this study was to complete an in-depth immunohistochemistry analysis of affected FCGS mucosa, to perform and compare immune cell phenotypes in the blood of FCGS and healthy controls cats, and to determine a transcriptomic profile of the affected and normal oral mucosa of FCGS cats. We hypothesized that cats with FCGS would have circulating activated CD8+ T cells and that tissues would be infiltrated with activated B and T cells with a highly proinflammatory transcriptome. We found that oral mucosal tissues from cats with FCGS have high tissue infiltration of B cells and that T cells include both CD4+ and CD8+ lymphocytes. Cells positive for CD25 (IL2 receptor, indicative of lymphocyte activation) and FOXP3 (indicative of regulatory T cells) were scattered throughout the mucosa. Compared to healthy individuals, cats with FCGS had high circulating CD8+ effector memory cells with a concurrent decrease in central memory cells and evidence of circulating activated CD8+ T cells (CD25+, CD62L−). Gene expression in the affected tissues was enriched for genes associated with T-cell signaling, cell adhesion molecules, leukocyte migration, inflammatory signaling pathways, extracellular matrix-receptor interactions, cytokine-cytokine receptor interactions, and natural killer cell-mediated cytotoxicity, among others. These data are essential to understand disease pathogenesis, to inform mechanism of action studies for future and current therapies, and to help select prognostic biomarkers and potency assays for stem cell treatment of FCGS.

A Case Series Analysis of Dental Extractions’ Outcome in Cats with Chronic Gingivostomatitis Carrying Retroviral Disease

“…Histopathological results show a lymphoplasmacytic infiltrate, indicative of the chronic inflammatory process. Polyclonal hypergammaglobulinemia is also a consistent finding [ 1 , 6 , 7 , 9 , 10 , 11 , 12 ].…”

“…FCGS is considered multifactorial, although recent evidence suggests a T-cell disfunction [ 12 ], related to infectious and non-infectious causes, such as viruses, dental plaque, hypersensitivity reactions, environment conditions and stress in multi-cat households [ 6 , 7 , 8 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. With regards to viral agents, feline calicivirus (FCV) appears to carry out a relevant role in FCGS, three times more prevalent in these animals when compared to the general cat population [ 2 , 15 ].…”

Environmental risk factors for the development of oral squamous cell carcinoma in cats

“…9,[13][14][15] The etiology of CGS is elusive and the pathogenesis is characterized by inappropriate immune response to an unknown antigenic stimulus, although underlying viral and bacterial etiologies have been proposed, including feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), and feline calicivirus. 16,17 In order to re-evaluate the previously proposed risk factors and to investigate further potential risk factors, including oral inflammation, we performed an observational epidemiological case-control study on cats with confirmed OSCC. Results were compared with an age-matched random sample of client-owned healthy cats and with 2 groups of cats having, respectively, CGS and PD.…”

Use of unbiased metagenomic and transcriptomic analyses to investigate the association between feline calicivirus and feline chronic gingivostomatitis in domestic cats

“…8,9 The predominance of CD8+ T cells within FCGS lesions suggests that the inflammation might be caused by a viral infection. 9,10 The possibility of respective associations between FCGS and multiple infectious agents, including FCV, FeLV, FIV, feline herpesvirus type 1, and Bartonella spp, has been investigated. 11-23,a,b Despite evidence suggesting a possible association between FCV and FCGS, results of multiple studies 12-16,18,19,21,23,24,a,b are inconsistent, and the role of FCV in FCGS remains uncertain.…”