No association between E- and L-selectin genes and SLE: soluble L-selectin levels do correlate with genotype and a subset in SLE.

Altered function of selectin glycoprotein adhesion molecules may modulate severity and organ-specific manifestations of autoimmune and inflammatory disease via changes in leukocyte trafficking. Serum concentrations of selectin molecules have been suggested as useful biomarkers in systemic lupus erythematosus (SLE). We identified increased levels of soluble L-selectin (sL-selectin), but not soluble E-selectin (sE-selectin) in 278 European-Caucasian lupus patients compared to 230 healthy siblings (P=0.002). sL-selectin levels were markedly elevated in patients with IgG antiphospholipid autoantibodies (P=0.002), suggesting that perhaps sL-selectin defines a subgroup of lupus with vasculopathy. sL-selectin level was also influenced by two L-selectin polymorphisms: 665C>T, F206L in the epidermal growth factor-like domain (P=0.015) and rs12938 in the 3'-untranslated region (P=0.06). Having shown increased sL-selectin levels in lupus patients, we used genetics to investigate whether this was a secondary phenomena or the result of an underlying genetic mechanism. The inheritance of nine single-nucleotide polymorphisms (SNP) spanning the selectin locus was tested in 523 UK simplex SLE families. No association with SLE, or related phenotypes, was evident with any single SNP, or haplotype in family-based tests of association. Selectin polymorphisms are, therefore, unlikely to be independent factors in SLE susceptibility.

Potential new therapeutic options in Behçet's syndrome.

Behçet's syndrome is a multisystem disorder that causes orogenital ulceration, skin lesions and intraocular inflammation with uveitis and retinal vasculitis. A proportion of affected individuals also develop vascular and central nervous system manifestations, with significant morbidity and mortality. Although the aetiopathogenesis of Behçet's syndrome is poorly understood, the condition is considered to be driven, at least in part, by autoimmune mechanisms. Conventional therapy relies on available anti-inflammatory and immunomodulatory agents, and, in view of the paucity of controlled clinical trials, it is to a large extent empirical. Oral ulcers can often be treated by topical application of corticosteroids. In addition to corticosteroids, agents used to treat ocular inflammation and significant systemic manifestations include colchicine, thalidomide, azathioprine, mycophenolate mofetil, cyclosporin, tacrolimus, cyclophosphamide and chlorambucil. The response to these agents is variable and there is a distinct need for more effective rational treatment. Over the last decade, a number of open studies have produced promising results using recombinant interferon-alpha preparations. Evaluating, in a methodical manner, the other new biological agents that are becoming available for the treatment of inflammatory diseases offers great promise, not only for effective management but also for providing insights into aetiopathogenesis.