Tulin Ergun

Oligoclonal T cell expansions in patients with Behçet's disease.

Behçets disease (BD) is a multisystem disorder with oral and genital ulcers, mucocutaneous, ocular, joint, vascular and central nervous system involvement. In this study, the peripheral T cell repertoire was analysed in patients with BD with MoAbs against T cell receptor (TCR) Vβ gene products in CD4+ and CD8+ T cell compartments, and these were compared with rheumatoid arthritis (RA) patients and healthy controls (HC). In the CD4+ T cell compartment, oligoclonal TCR Vβ expression was observed in 56% of BD (10/18), 71% of RA (5/7) patients and 21% (3/14) of HC. In the CD8+ T cell group 50% of BD (9/18), 57% of RA patients and 28% of HC (4/14) had an oligoclonal TCR repertoire. An increase of TCR Vβ5.1 subset was observed in five BD patients among CD8+ T cells. Other elevations of TCR Vβ subsets were heterogeneously distributed with one to three different Vβ subsets. Our results suggest an antigen‐driven oligoclonal increase of T cells in BD. There was no overall increase in any Vβ group to suggest a superantigen effect. Analysis of the responsible antigens causing the increase in T cell subsets may give insights into the aetiopathogenesis of BD and immunomodulation of these T cells may lead to new treatments.

Behçet's disease in patients with chronic myelogenous leukemia: possible role of interferon-alpha treatment in the occurrence of Behçet's symptoms.

Abstract Two patients with chronic myelogenous leukemia (CML) who developed characteristic features of Behçets disease (BD) during alpha-interferon (IFN-α) treatment and another patient who had a diagnosis of BD preceding CML are presented. In the first two patients, features of BD appeared 6 months after the initiation of IFN-α treatment; they included recurrent oral aphthae, genital ulceration, arthritis, folliculitis, and a positive skin pathergy test. The third patient, however, had a diagnosis of Behçets disease 4 years before diagnosis of Philadelphia-positive CML. We prospectively examined the skin pathergy reaction in a group of patients with CML, multiple myeloma, and hairy cell leukemia both before and after IFN-α treatment and found two additional patients with CML who developed a positive skin pathergy test following IFN-α treatment.

Increased CD4+CD16+ and CD4+CD56+ T cell subsets in Behçet's disease

Abstract Behçets disease is a systemic vasculitis of unknown etiology. Various immune abnormalities have previously been shown in Behçets disease. We investigated T lymphocyte subsets associated with cytotoxic activity and natural killer (NK) cells by flow cytometry in 37 patients with Behçets disease, 38 healthy controls, and 17 diseased control patients. Compared to the healthy controls, CD4+CD16+ and CD4+CD56+ subsets were found to be higher in the Behçets disease group as well as in the disease control group (CD4+CD16+: BD=5 ± 3, DC=14 ± 14, HC= 3 ± 2, P=0.001; CD4+CD56+: BD=11 ± 5, DC= 18 ± 17, HC=8 ± 6, P=0.01). CD8+CD16+ and CD8+CD56+ T cell subsets were at normal levels in Behçets disease but found to be elevated in disease controls. Similarly, NK cells (CD16+CD56+) were high only in the disease control group. Significant increases in CD4+CD16+ and CD4+CD56+ cell subsets in Behçets patients and disease controls suggest that T cell activation patterns of these subsets in Behçets disease are similar to those in other inflammatory disorders.

Successful use of etanercept in type I pityriasis rubra pilaris

M. DA I BATA* M. TOHYAMA J . BATCHE LOR K. HASH IMOTO M. I I J IMA Department of Dermatology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan *Department of Haematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku City, Kochi 783-8505, Japan Department of Dermatology, Ehime University School of Medicine, Onsen-gun, Ehime 791-0295, Japan Department of Dermatology, Addenbrooke’s Hospital, Cambridge, U.K. E-mail: hwatanabe@med.showa-u.ac.jp

Skin manifestations of rheumatoid arthritis: a study of 215 Turkish patients.

Objective  To investigate the frequency and clinicopathological features of skin involvement in rheumatoid arthritis (RA), to find out whether early and aggressive disease‐modifying treatment is changing the spectrum towards a milder disease pattern.

Efficacy of oral fluconazole in the treatment of seborrheic dermatitis: a placebo-controlled study.

AbstractBackground: Seborrheic dermatitis (SD) is a common, chronic dermatosis. Although the pathogenetic mechanisms of SD are not clear, Malassezia spp. yeasts are known to cause the disease. Previous studies have shown that topical and systemic antifungals provide clinical benefit. Objective: To evaluate the safety and efficacy of short-term oral fluconazole in patients with SD. Methods: Sixty-three patients with mild-to-moderate SD were randomly allocated to receive either oral fluconazole 300mg in a single dose per week or placebo, for 2 weeks. Twenty-seven patients taking fluconazole and 23 patients taking placebo completed the study and were analyzed. The SD area severity index (SDASI) score and the patient’s subjective assessment of pruritus and burning sensation were evaluated before and after treatment. Both the investigator and the patients were blinded to treatment. Results: A statistically significant improvement in SDASI score after treatment compared with baseline was obtained with fluconazole (p = 0.01) but not with placebo. However, the difference between the treatment groups was not statistically significant (p > 0.05). Subjective improvements in symptoms, such as pruritus and burning sensation, were observed in both groups but no statistically significant differences versus baseline were seen. Conclusion: The results of this study indicate that fluconazole provides marginal and statistically insignificant benefit for the therapy of SD. However, larger studies using different dosages and/or durations of fluconazole therapy may provide a rationale for systemic use of fluconazole in SD.

Salivary levels of antimicrobial peptides Hnp 1-3, Ll-37 and S100 in Behcet's disease

BACKGROUND Oral ulcer is the cardinal clinical sign and increased neutrophilic activity is a part of the pathogenesis in Behcets disease (BD). Saliva, as a part of the innate immune response, contains antimicrobial peptides (AMPs) that are derived from both oral epithelial cells and neutrophils. The aim of this study was to investigate the associations between salivary levels of AMPs HNP 1-3, LL-37 and S100 and disease course in patients with Behcets disease (BD). METHODS Fifty-three patients with BD and 44 healthy controls (HC) were included in the study. Disease severity score reflecting organ involvement was calculated. Salivary HNP 1-3, LL-37 and S100 levels were measured in unstimulated saliva samples by ELISA. RESULTS Salivary HNP 1-3 and S100 levels in BD patients (2715.2 ± 1333.4 μg/ml and 430.6 ± 203.9 ng/ml) were significantly higher compared to HC (1780.6 ± 933.2 μg/ml and 365.3 ± 84.7 ng/ml) (p = 0.000 and p = 0.004, respectively). Although LL-37 levels were also higher in BD than HC (190.9 ± 189.1 vs 143.1 ± 128.9 ng/ml), no significant difference was observed (p = 0.53). Salivary HNP 1-3 and LL-37 levels were associated with the severity of BD (mild disease: 1975.1 ± 1174.2 μg/ml and 115.9 ± 109.4 ng/ml vs severe disease: 2955.7 ± 1305.6 μg/ml and 215.3 ± 203.8 ng/ml, p=0.020 and p=0.031, respectively). Salivary LL-37 levels also correlated with the number of monthly oral ulcers (r = 0.5 p = 0.000). CONCLUSION An increase in salivary HNP 1-3 and S100 levels might be associated with enhanced local and systemic innate responses in BD.

Sequencing of 16S rRNA reveals a distinct salivary microbiome signature in Behçet's disease

Behçets disease (BD) is characterized by recurrent oro-genital ulcers, mucocutaneous lesions, and serious organ involvement. We investigated the salivary microbiome in BD using high-throughput sequencing of the 16S rRNA V4 region. Stimulated saliva samples were collected from 31 BD patients and 15 healthy controls, and in 9 BD patients, a second saliva sample was collected following dental and periodontal treatment. Sequence analysis identified a total of 908 operational taxonomic units (OTUs) present across all samples. Patients had a microbial community structure that is significantly less diverse than healthy controls. The most overabundant species in BD was Haemophilus parainfluenzae, while the most depleted included Alloprevotella rava and species in the genus Leptotrichia. Periodontal treatment improved oral health indices in BD but had no short-term effect on bacterial community structure. Neither the BD-associated genetic risk locus within the HLA-B/MICA region nor being on immunosuppressive medications explained the differences between patients and controls.

Isotretinoin has no negative effect on attention, executive function and mood.

Background  According to some animal data, impairments in learning and memory are seen with isotretinoin. Isotretinoin has been shown to affect human brain metabolism, but the data on human neural functions is lacking.

Phagocytosis and oxidative burst by neutrophils in patients with recurrent furunculosis

Neutrophil phagocytosis of fluorescently labelled Staphylococcus aureus and oxidative burst by the neutrophils were assessed by flow cytometry in 22 patients with recurrent furunculosis and in 17 controls. Phagocytosis and oxidative burst were not found to be significantly different between the patients and controls. Low serum iron concentrations were demonstrated in six patients (27%). In these patients with hypoferraemia, oxidative burst was significantly lower than in the patients without hypoferraemia and in the controls. These data suggest that hypoferraemia may be an important predisposing factor in a subgroup of patients with recurrent furunculosis in impairing oxidative killing by neutrophils.