Anti-E-selectin is ineffective in the treatment of psoriasis: a randomized trial.

BACKGROUND: Skin-homing, memory T lymphocytes play an important role in the pathogenesis of psoriasis by interacting with the vascular addressin, E-selectin and trafficking into lesional skin. Thus an attractive option for targeted therapy of the disease would be blockade of skin-homing T cells with an antibody directed at E-selectin. OBJECTIVE: We performed a multicentre, randomized, placebo-controlled trial to investigate the clinical efficacy and side-effect profile of a humanized monoclonal antibody to E-selectin, CDP850, in the treatment of moderate to severe chronic plaque psoriasis. METHODS: Patients with moderate/severe chronic plaque psoriasis were selected for study. Nine male subjects (mean age 37 years, range 25-47) were given 20 mg kg-1 CDP850 intravenously as a single dose and four subjects (three males, one female; mean age 40 years, range 23-50) received placebo infusion. Clinical response to treatment was assessed using the psoriasis area and severity index (PASI). Skin biopsies were taken for immunohistochemical analysis at the baseline, pretreatment, visit and also at day 2 and weeks 1 and 4 postinfusion. RESULTS: The treatment was well-tolerated with a minimal side-effect profile. Plasma E-selectin levels were significantly decreased in those subjects who received CDP850 compared with those who had placebo for the entire study period. At the end of study (8 weeks postinfusion), there was no significant reduction in PASI from baseline for either the CDP850 or placebo-treated groups. Immunohistochemical analysis of biopsies taken from lesional psoriatic skin showed that 2 days after dosing with CDP850, staining for E-selectin was decreased, although not absent, on dermal vascular endothelial cells when compared with baseline (P < 0.01). This decrease in E-selectin expression was maintained 4 weeks after infusion (P < 0.05). It was not, however, accompanied by a significant reduction in numbers of neutrophils or lymphocytes in the dermis. There was a statistically significant increase in CD1a-positive epidermal Langerhans cells compared with pre-dose levels at week 1 (P < 0.05). CONCLUSIONS: This clinicopathological study shows that anti-E-selectin (CDP850), although a well-tolerated, logical and safe therapy, does not appear to possess a therapeutic role in the treatment of chronic plaque psoriasis.

Impaired secretory immunity in dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa is a congenital disorder characterized by blistering of the skin and oral mucosa. This study investigated the hypothesis that children with dystrophic epidermolysis bullosa have impaired oral secretory immunity. Immunoglobulin A (IgA), secretory IgA and IgG concentrations, and IgA and secretory IgA antibody levels to Candida albicans, Lactobacillus casei and Streptococcus mutans were measured in whole saliva from 22 children with dystrophic epidermolysis bullosa and 22 matched controls. Salivary total IgA and total IgG concentrations were significantly raised in dystrophic epidermolysis bullosa due to serum leakage from oral blistering, but the converse was seen with secretory IgA. This suggestion of a mucosal immune defect was supported by decreased secretory IgA antibody responses to all three microorganisms tested. This apparent defect in secretory immunity in dystrophic epidermolysis bullosa may be due to mucosal involvement and damage resulting in impaired antigen sampling in mucosal associated lymphoid tissue or to impaired transport of secretory IgA across the salivary gland mucosa.