A cross-sectional study on activity impairment in primary Sjogren's syndrome.

OBJECTIVE: The aim of this cross-sectional study was to show relations between activity impairment and salivary gland involvement for patient empowerment in primary Sjogren's syndrome (pSS). METHODS: In the study, 86 patients with pSS were included. The data were collected through clinical examinations and a questionnaire regarding Work Productivity and Activity Impairment (WPAI), EULAR Sjogren's syndrome patient-reported index (ESSPRI) and Oral Health Impact Profile-14 (OHIP-14). Relations were analysed by using mediation and moderation analyses. In simple mediation analysis, an independent variable (X) influences outcome variable (Y) through a mediator variable (M) whereas a moderator variable (W) affects the direction of the relationship between the dependent (Y) and independent variables (X). RESULTS: Increases in ESSPRI-Dryness score (X) (p = 0.0189) and OHIP-14 score (M) (p = 0.0004) were associated with the poor WPAI activity impairment score (Y) in the first mediation analysis. The WPAI activity impairment score was mediated by the elevated ESSPRI-Fatigue score (X) (p = 0.03641) and low U-SFR (M) (p = 0.0000) in the second mediation analysis. In addition, ESSPRI-Pain score (W) was the significant moderator for WPAI activity impairment (Y) in patients without hyposalivation in the moderation analysis (p = 0.0010). CONCLUSION: WPAI activity impairment was affected by both ESSPRI-Dryness with OHRQoL and ESSPRI-Fatigue with SFR in glandular involvement.

Th17-Inducing Conditions Lead to in vitro Activation of Both Th17 and Th1 Responses in Behcet's Disease.

OBJECTIVES: Interleukin-17 (IL-17) has been associated with the pathogenesis of various autoimmune/inflammatory diseases. The aim of this study was to investigate the expression of Th17-related immunity in an innate immunity-dominated vasculitis, namely Behcet's disease (BD). METHODS: Peripheral blood mononuclear cells from 37 patients (age: 38.5 ± 9.8 years) with BD, and 25 healthy controls (HC) (age: 39.1 ± 9.3 years), were cultured in Th17-inducing conditions (IL-6, Phytohemagglutinin (PHA), IL-1ß, and IL-23) for 6 days. Cultured cells were stained with CD4, CD8, CD3, TCR gamma/delta, CD19, interferon-γ (IFN-γ), and IL-17 antibodies to determine the intracellular cytokine secretion by flow cytometry. RESULTS: IL-17 expression by CD8+ and γδ+ T cells was higher in BD compared to HC (p = 0.004, p = 0.003, respectively). No differences were observed between the groups in the IL-17 production by B cells. Under Th17-inducing conditions, production of IFN-γ by CD4+, CD8+, and γδ+ T cells was also higher in BD compared to HC (p < 0.05 in all). CONCLUSION: Our results suggest that under Th17-stimulating conditions, T cells express both IL-17 and IFN-γ in BD. More prominent IL-17 and IFN-γ production by all lymphocyte subsets in BD might be associated with the increased innate responses, early tissue neutrophil infiltrations and late adaptive immunity in BD.

Pro-inflammatory cytokine and caspase-1 responses to pattern recognition receptor activation of neutrophils and dendritic cells in Behcet's disease.

OBJECTIVE: Activated innate immunity is implicated in the pathogenesis of Behcet's disease (BD). To clarify the mechanisms of innate immune responses, we investigated inflammasome activation in dendritic cells (DCs) and neutrophils, following stimulation with two different pattern recognition receptors (PRRs) RIG-1-like (RLR) and NOD-like (NLR) in patients with BD. METHODS: Sixteen active BD patients with mucocutaneous lesions and 17 healthy controls (HCs) were included in this study. DCs were generated from monocytes. DCs and isolated neutrophils were activated by RLR and NLR ligands. Caspase-1 activation and expression of p38 and RIP2 were determined by flow cytometry. Levels of IL-1ß, IL-6, TNF-α, IFN-α and IL-18 in culture supernatants were measured by ELISA. RESULTS: Activation of caspase-1 following intracellular PRR stimulation was found to be of similar levels in DCs and neutrophils of BD patients compared with HCs. However, activation of DCs from BD patients to NOD2 stimulus measured by the expression of RIP2 and p38 as well as IL-18 levels was found to be slightly defective (P < 0.05). In neutrophil cultures, IL-6 levels were lower in response to all stimuli in patients with BD compared with HCs (P < 0.01). CONCLUSION: Inflammasome formation following stimulation with NOD1/NOD2 and RIG measured by caspase-1 activation, cytokine levels and expression of RIP2 and p38 seems to be functionally normal in DCs and neutrophils of BD patients, although slightly defective responses in some pathways and cytokine levels were observed. These results may suggest that caspase-1-independent pathways such as toll-like receptors may be more prominent in BD pathogenesis.