Activation of neutrophils by testosterone in Behçet's disease.

OBJECTIVE: Gender differences, especially in disease severity, are observed in Behçet's disease (BD), a systemic vasculitis of unknown etiology. To determine the putative role of testosterone on neutrophil activity exhibited by patients with BD, peripheral blood neutrophils were examined in vitro before and after treatment with testosterone. METHODS: Peripheral blood neutrophils of 49 patients with BD (26M:23F), 33 patients with ankylosing spondylitis (AS) (23M:10F), 8 female patients with hirsutism and 31 healthy individuals (19M:12F) were analyzed by flow cytometry. Neutrophil-ROS-generating capacity, anti-CD66b, anti-CD16, Phi-philux and PI staining techniques were used for evaluating neutrophil activation and apoptosis. RESULTS: Gender differences were striking not only in the mean oxidative burst response but also in the rate of apoptosis. Male BD patients manifested increased burst response before testosterone treatment compared with females (8.0 +/- 4.9 vs. 4.9 +/- 3.3, p < 0.01). Consistent with oxidative burst results, baseline percentages of CD66b (99.1 +/- 0.9 vs. 94.7 +/- 5.3 p < 0.04) and CD16 expressing cells were greater in male BD patients. A decreased apoptosis ratio was observed using phi-philux and PI staining in BD patients. This was especially significant in male compared to female BD patients (2.4 +/- 1.4 vs. 6.8 +/- 5.8, p < 0.002). BD itself rather than the gender was found to be the most important predictor of this altered apoptosis ratio in BD determined by linear regression analysis. CONCLUSION: Our results suggest that a contribution of testosterone to the BD pathogenesis cannot be ruled out. However, causative factors for disturbed apoptosis especially seen in male BD patients need to be further evaluated.

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis.

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.

Oxidative burst response to monosodium urate crystals in patients with Behçet's syndrome.

OBJECTIVE: An erythematous response to intradermal injection of monosodium urate crystals (MSU) has been demonstrated in Behçet's syndrome (BS). To further elucidate the pathogenesis of this response, the effects of MSU on in vitro oxidative burst reaction of neutrophils and monocytes were investigated. METHODS: Peripheral blood mononuclear cells from patients with Behçet's syndrome (BS), rheumatoid arthritis (RA), familial Mediterranean fever (FMF) and healthy controls (HC) were incubated with 100 ng/ml phorbol myristate acetate (PMA) and MSU at different dosages (25-500 microg/ml). Oxidative burst reaction was evaluated in neutrophils and monocytes by flow cytometry. RESULTS: In patients with BS, oxidative burst of neutrophils was significantly increased compared to HC at 125 microg/ml and 250 microg/ml dosages of MSU (p < or = 0.001 and 0.004 respectively). In patients with FMF; there was also an increased oxidative burst reaction at 75 microg/ml, 250 g/ml and 500 microg/ml (p < or = 0.007; 0.001 and 0.004 respectively). In patients with BS, oxidative burst of monocytes was increased only at 125 g/ml dosage of MSU (p < or = 0.002). However, in patients with FMF monocyte burst response was increased at 25 microg/ml, 75 microg/ml and 125 g/ml (p < or = 0.004; < 0.0001; < 0.0001 and 0.002 respectively). In RA group, stimulation with PMA resulted in a higher oxidative burst reaction than FMF and BS (p < or = 0.000 and p < or = 0.008). No correlation was observed between oxidative burst of neutrophils or monocytes and intradermal responses to MSU crystals. CONCLUSION: Oxidative burst reaction with MSU is augmented in neutrophils and monocytes of BS. However, the response is not specific and is unassociated with skin dermal test which has a high specificity for BS.

Clinical and immunological effects of azithromycin in Behçet's disease.

BACKGROUND: The aim of this study was to evaluate the effects of azithromycin on mucocutaneous manifestations, oral health and immune response in Behçet's disease (BD). METHODS: Eight BD patients with active mucocutaneous symptoms were treated with azithromycin for 4 weeks. Oral health, clinical manifestations and in vitro interleukin (IL)-12, interferon (IFN)-gamma, IL-10 and monocyte chemotactic protein (MCP)-1 responses were evaluated before and after treatment. RESULTS: The number of folliculitic lesions, healing time of oral ulcers and scores of plaque indexes (PLIs) were lower after azithromycin treatment (P<0.05). Scores of PLIs correlated positively with the healing time of oral ulcers (P=0.02). Although a trend towards increased stimulated IL-10 responses with azithromycin was observed, no statistically significant difference was found. Stimulated and unstimulated MCP-1, IFN-gamma and IL-12 responses were similar before and after treatment (P>0.05). CONCLUSION: Azithromycin was observed to be effective in decreasing folliculitic lesions and fastening the healing time of oral ulcers in BD.