Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet's Disease.

Behçet's disease (BD) is a chronic, multi-systemic disorder of unknown aetiology typified by recurrent oral and genital mucocutaneous lesions, uveitis and vasculitis. Innate and adaptive immune system dysregulation has been implicated in pathogenesis with alterations in serum cytokine profiles. Few studies have investigated salivary cytokines in BD, despite more than 90% of BD patients first presenting with oral ulceration. The aim of this pilot study was twofold; firstly to investigate whether cytokine levels in matched serum and saliva samples show a differential profile in BD (with and without oral ulcers), recurrent aphthous stomatitis (RAS) and healthy controls (HCs), and secondly, to explore if any differential profiles in serum and/or saliva could provide a panel of cytokines with diagnostic and therapeutic potential for BD. Concentrations of 12 cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, TNF-ß) were measured using the Human Th1/Th2 11-Plex FlowCytomix™ kit with IL-17A, in BD (N=20), RAS (N=6) and HCs (N=10). A differential range of cytokines was detected in serum and saliva with the majority of cytokine levels higher in saliva. The most prevalent salivary cytokines were IL-1ß, IL-2, IL-8, IL-10 and TNF-α present in all samples in contrast to serum where the most prevalent cytokine detected was IL-8 (91.9%). The least abundant cytokine was IFN-γ in both saliva (43.2%) and serum (2.7%). After normalizing saliva for protein content, BD patients with oral ulcers (BD-MA) had significantly higher levels of salivary IL-1ß (p=0.01), IL-8 (p=0.02), TNF-α (p=0.004) and IL-6 (p=0.01) than HCs. Notably, BD patients without oral ulcers (BD-MQ) also had significantly higher salivary IL-1ß, IL-8 and TNF-α (p ≤ 0.05) than HCs. During relapsed (BD-RE) and quiet (BD-Q) systemic episodes, salivary IL-ß and TNF-α were also significantly increased with IL-8 significantly higher only in BD-Q (p=0.02). BD oral ulcers signify a potential reactivation of systemic inflammation. Identifying cytokines released during asymptomatic episodes and oral ulceration might lead to targeted drug therapy to prevent recurrent oral ulcers and possible disease relapse. This is the first study to report salivary cytokine levels in BD. The detectable levels suggests cytokine profiling of BD saliva may provide an alternative, less invasive, sensitive procedure for frequent monitoring of disease activity and progression.

Gamma Delta (γδ) T Cells and Their Involvement in Behçet's Disease.

Behçet's disease (BD) is a multisystem inflammatory disorder characterized by orogenital ulcerations, ocular manifestations, arthritis, and vasculitis. The disease follows a relapsing-remitting course and its pathogenesis is unknown. Genetic predisposition and immune-dysregulation involving gamma delta (γδ) T cells are reported to have a role. γδ T cells are atypical T cells, which represent a small proportion of total lymphocytes. They have features of both innate and adaptive immunity and express characteristics of conventional T cells, natural killer cells, and myeloid antigen presenting cells. These unconventional T cells are found in the inflammatory BD lesions and have been suggested to be responsible for inducing and/or maintaining the proinflammatory environment characteristic of the disease. Over the last 20 years there has been much interest in the role of γδ T cells in BD. We review the literature and discuss the roles that γδ T cells may play in BD pathogenesis.

Genital ulcer severity score and genital health quality of life in Behçet's disease.

BACKGROUND: Behçet's Disease (BD) is a chronic auto-inflammatory, multisystem relapsing/remitting disorder of unknown aetiology. Oro-genital ulceration is a key feature of the disease and has a major impact on the patients' quality of life. Other clinical manifestations include ocular inflammation, rheumatologic and skin involvement, while CNS and vascular complications can lead to considerable morbidity. The availability of a valid monitoring tool for BD activity is crucial in evaluating the impact of the disease on daily life activity. The aims of this study were to validate a novel tool for monitoring genital ulceration severity in BD and to assess the impact of genital ulcers on the Genital Health Quality of Life (GHQoL). METHODS: Genital Ulcer Severity Score (GUSS) was developed using six genital ulcer characteristics: number, size, duration, ulcer-free period, pain and site. A total of 207 BD patients were examined, (137 females: mean age ± SD: 39.83 ± 13.42 and 70 males: mean age ± SD: 39.98 ± 11.95) from the multidisciplinary Behçet's Centre of Excellence at Barts Health NHS Trust. GUSS was used in conjunction with Behçet's Disease Current Activity Form (BDCAF). RESULTS: The over-all score of GUSS showed a strong correlation with all genital ulcer characteristics, and the strongest correlation was with the pain domain (r = 0.936; P < 0.0001). Ulcer average size and ulcer pain were the major predicting factors in GUSS (ß = 0.284; ß = 0.275) respectively, and P-values were significant. Multivariate regression analysis indicated that the ulcer pain, size and site are the main ulcer characteristics having an influence on the GHQoL (R(2): 0.600; P < 0.0001). CONCLUSIONS: This study established the practicality of GUSS as a severity monitoring tool for BD genital ulcers and validated its use in 207 patients. Genital ulcers of BD have a considerable impact on the patients GHQoL.