Association of small ubiquitin-like modifier 4 (SUMO4) polymorphisms in a Tunisian population with Behçet's disease.

OBJECTIVES: An association of SUMO4 gene, which has recently been shown to be a negative feedback regulator for nuclear factor NF-κB, has been reported in several autoimmune/inflammatory diseases. A case-control study was set up to investigate the contribution of SUMO4 locus to the genetic susceptibility to Behçet's disease (BD). METHODS: One hundred and thirty-five Tunisian BD patients and 167 healthy blood donors from the same geographical area were genotyped by polymerase chain reaction for the SUMO4 polymorphisms. RESULTS. The SUMO4+438 C allele frequency is significantly increased in BD patients (p=0.03; χ2=4.71; OR=1.44; 95% CI=1.02-2.04) and highly significantly increased in HLA-B51 positive BD patients (p=3 10-6; χ2=21.62; OR=4.44; 95% CI=2.21-8.98). Similarly, the SUMO4 -847 G allele frequency is significantly increased in BD patients (p=0.03; χ2=4.34; OR=1.41; 95% CI=1.01-1.97). The studied polymorphisms were also associated with disease severity, skin lesions and vascular involvement. CONCLUSIONS: SUMO4+438 C and -847 G alleles seem to be associated with susceptibility to BD in Tunisian population. We suggest that SUMO4 gene polymorphisms may be involved in the development of skin lesions, vascular BD, as well as the severity of the disease.

Tumor necrosis factor gene polymorphisms in Tunisian patients with Behcet's disease.

Behcet's disease (BD) is an inflammatory disorder that is mainly characterized by recurrent oral and genital ulcers, skin lesions, and uveitis. Recent reports focused on the genetic factors of susceptibility to this disease and especially the TNF in view of the major role played by this proinflammatory cytokine in the lesional process of Behcet's disease. In this report, we investigated the possible association between Behcet's disease and the TNF-alpha gene promoter polymorphisms -1031T/C, -308A/G, and the TNF-beta polymorphism +252A/G in Tunisian population. We compared the distribution of these polymorphisms between 89 BD patients and 157 healthy controls using polymerase chain reaction restriction fragment length-polymorphism (PCR-RFLP) analysis. The frequency of the TNF-alpha -1031C allele was significantly higher in Behcet's patients than in healthy controls (p = 0.015; chi(2) = 5.84; OR = 1.65; 95% CI = 1.08-2.54), whereas the frequencies of the TNF-alpha -308G and the TNF-beta +252G alleles were similar in the two compared groups. These results suggest that the variability of the TNF-alpha -1031T/C polymorphism can be associated with the susceptibility to Behcet's disease in our study group. Therefore, the TNF molecule may have an important genetically and/or functionally implication in the pathogenesis of BD in the Tunisian population.

Increased endothelin-1 levels of BAL fluid in patients with Behçet's disease.

OBJECTIVE AND BACKGROUND: Pulmonary aneurysms and thrombosis constitute a significant cause of morbidity and mortality in Behçet's disease (BD). Various factors have been studied to explore the pathogenesis of vascular involvement in BD. As endothelin (ET) is known for its potent vasoconstrictor and proinflammatory properties, we supposed that it is involved during the inflammatory process of BD pulmonary vasculitis. METHODS: To investigate the role of ET in BD, ET-1 concentrations were measured in bronchoalveolar lavage fluid (BALF) of 18 nonsmoking BD patients with pulmonary manifestations and 12 control subjects. Immunoreactivity of ET-1 was also evaluated in alveolar macrophages (AMs) cytoplasm. RESULTS: ET-1 levels in BD-BALF were significantly higher than those of controls. ET-1 levels were correlated with the number of alveolar macrophages, but not with BAL-CD4/CD8 ratio. ET-1-immunoreactivity was found mainly in AM of BD-BAL. CONCLUSIONS: Increased ET-1 production from AM is associated with pulmonary BD manifestations.

Discrepancies of NKT cells expression in peripheral blood and in cerebrospinal fluid from Behçet's disease.

The precise role of natural killer T (NKT) cells in the pathogenesis of Behçet's disease (BD) remains unknown. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMC) from 42BD patients and in cerebrospinal fluid (CSF) samples from 9 neuro-BD patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMC from BD patients (median: 0.06%; range: 0%-0.3%) when compared to healthy controls (median: 0.23%; range: 0.1%-0.7%; P<0.01). NKT cells were biased toward a Th(1)-like phenotype, with a significant decrease of IL-4/IFN-gamma ratio in BD (median: 0.049; range: 0.01-0.13) vs. healthy controls (median: 0.82; range: 0.4-1.33; P<0.01). NKT cells were increased in CSF-BD samples (median: 0.18%; range: 0.1%-0.4%), when compared to CSF-NIND patients (median: 0.05%; range: 0.01%-0.09%; P<0.01). Based on the reactivity of PBMC-derived NKT cells toward alpha-galactosylceramide (alpha-GalCer), 80% of BD patients were non-responsive. At the opposite, the reactivity of NKT cells in CSF from BD patients was not impaired. BD-CSF NKT cells exhibited an increased expression of IFN-gamma-producing cells, demonstrating that CSF-NKT cells were functional, and biased toward a Th(1)-like phenotype. These data suggest that functional NKT cells are recruited into BD inflammatory sites contributing to BD pathogenesis.