Coagulation factor V gene mutation increases the risk of venous thrombosis in Behcet's disease

We investigated the prevalence of the coagulation factor V gene G1691A mutation in 64 patients with Behcet's disease (BD) and in 107 apparently healthy individuals. The mutation was present in the heterozygous state in 37.5% of the patients with a history of deep vein thrombosis (12/32) and in 9.4% of the patients without any thrombotic event (3/32). Eleven healthy individuals were also heterozygous for the mutation (10.3%). The prevalence of the mutation in BD patients with and without thrombosis was significantly different (P = 0.0079). We conclude that the factor V gene mutation may play a major role in the development of venous thrombosis in BD

Immunohistology of Skin Pathergy Reaction in Behçet's Disease

The immunophenotypic characteristics of the skin pathergy reaction (SPR) at 48 h in Behçet's disease (BD) were investigated in 12 patients with BD and in five controls. The findings in 11 positive and one negative SPR lesions of patients with BD were evaluated in comparison with those of normal adjacent skin and with the negative pathergy biopsies from the controls. Positive SPR biopsies showed variable epidermal thickening and cell vacuolization, as well as subcorneal pustule formation. In the SPR dermis, a variable dense focal mononuclear cell (MNC) infiltrate was seen around vessels and skin appendages, extending into the deep dermis. The MNC infiltrate was predominantly composed of T lymphocytes and monocytes/macrophages. The majority of the T lymphocytes were CD4+, and almost all expressed CD45RO. Approximately half of the infiltrating cells strongly expressed HLA-DR. Neutrophils constituted less than 5% of the infiltrating cells, but were present as clusters of elastase-positive cells at the needle-prick sites. Vessels within the lesion showed marked congestion and endothelial swelling. The endothelial cells expressed ICAM-1 strongly, and E-selectin moderately. VCAM-1 was not expressed on endothelial cells. The basal and mid-epidermal layers of keratinocytes expressed HLA-DR and ICAM-1 strongly, particularly so in areas close to the dermal MNC infiltrates. In negative pathergy biopsies, there were increased numbers of neutrophils and a few small clusters of macrophages and T lymphocytes only at the needle-prick site, and the endothelial cells of vessels close to these areas expressed E-selectin weakly. The immunohistological findings of the SPR appear to indicate an augmented antigen-independent non-specific induction phase of the inflammatory response. Absence of VCAM-1 expression by endothelial cells suggests that direct epidermal injury is the cause of the cutaneous inflammation

Peripheral blood T cell expansions in patients with Behcet's disease

Behcet's disease (BD) is a chronic multisystemic inflammatory disorder characterized mainly by recurrent oral and genital aphthous ulcerations and uveitis. Etiology and pathogenesis of BD remain unknown. T cell receptor (TCR) V alpha/V beta gene product expression as well as J beta gene segment expression in peripheral blood of BD patients were analysed to investigate the possible role of T lymphocytes in the etiopathogenesis of BD. Flow cytometry with 12 TCR V-specific MoAbs was used for TCRV analyses. J beta gene segment usage by T cell populations expressing certain V beta s was determined by polymerase chain reaction (PCR) technique with V beta- and C beta-specific primers, Southern blotting of PCR products, and subsequent hybridization with radiolabelled J beta gene segment-specific probes. Although 13 of the 23 BD patients exhibited increases in expression of one or more TCR V-gene products, only expansions among the CD4(+) T cell subset were significantly more frequent in BD patients (7/23) compared with healthy controls (0/15) (P = 0.019). Six out of eight cases followed for up to 20 months had at least one expansion correlated with disease activity. A strict preference for particular J beta gene segments implicating clonality was apparent in all analysed T cell expansions and correlated well with disease activity. These results suggest a possible involvement of antigen-specific T lymphocytes in the pathogenesis of BD