Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease

Behcet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production

A new kind of skin lesion in Behçet's disease: extragenital ulcerations.

A new skin lesion was encountered in 29 of 970 Behcet's patients. The lesions resembled oral aphthae clinically, were recurrent and left a scar tissue like genital ulcers but were located extragenitally. Skin biopsies could be done in only 4 cases and they all showed vasculitis

Pemphigus vulgaris localized to the nose and cheeks

Pemphigus vulgaris is an autoimmune blistering disease characterized by disseminated bullae and erosions of the mucosal surfaces and skin. Cases of pemphigus vulgaris with localized lesions on glabrous skin have been reported, and most of them have been attributed to the Koebner phenomenon. Lesions limited to the nose have mostly been described in pemphigus foliaceus, but the nose has also been the initial site of pemphigus vulgaris in a few patients. We report 4 cases of localized pemphigus vulgaris: one case with lesions limited to the nose and cheeks and 3 cases with isolated lesions on the nose. Recurrent episodes in these patients also occurred on the nose. None of them showed mucosal involvement or dissemination during a follow-up period of 2 to 9 years. Three patients had autoantibodies against desmoglein-3 as detected by immunoblot. In the other patient, antibodies against desmoglein-3 were detected by enzyme-linked immunosorbent assay. These localized lesions may represent a subgroup of pemphigus vulgaris or a period of limited activity during this chronic disease

The association of HLA-B5 antigen with specific manifestations of Behçet's disease.

The HLA-BS phenotype was investigated in 235 patients with Behcet's disease and in 100 healthy persons. HLA-BS was more frequent in the patients (77 vs. 30% p<0.001, relative risk=7.8). The frequency of HLA-BS was higher in patients with genital ulceration than without (82.3 vs. 63%, p<0.01). Patients with thrombophlebitis showed a less frequent positivity of HLA-BS antigen than the patients without thrombophlebitis (50 vs. 79.2%, p<0.02). These results suggest that HLA-BS-related genes not only affect the development of Behcet's disease but also the occurrence of its clinical manifestations