Detection of cytotoxic anti-LEDGF autoantibodies in atopic dermatitis

In the last two decades, atopic dermatitis (AD) has been of increasing clinical significance in Japan. Eight-20% of patients with AD developed progressive cataracts (cataract-AD) and lens epithelial cells (LECs) were severely damaged. Lens epithelium-derived growth factor (LEDGE) is a newly isolated survival factor. In the presence of LEDGE, LECs survive well and in the absence of LEDGE, they become highly susceptible to stress. We investigated (1) whether auto-antibody (auto-Ab) to LEDGE is present in sera of AD patients and (2) whether depletion of LEDGE by the auto-Ab kills LECs. In sera from 26 patients with AD using ELISA, we found significantly higher levels of auto-Ab to LEDGE than that in a normal control group. Affinity purified auto-Ab to LEDGE from these sera killed LECs without complement activation. Levels of histamine in the AD group were significantly higher and levels of prostaglandin E2 were significantly lower than in the normal group. However, statistically there are no differences between sera from AD and cataract-AD in levels of Ab to LEDGE, histamine, prostaglandin E-2 (PGE(2)), immunoglobulin E (IgE) and eosinophiles. We speculate that cataract-AD may be induced, in part, by a combination of high levels of serum histamine and eye rubbing which could break the blood-aqueous barrier to allow the entry of Ab to LEDGE into the privileged compartment, thus, reducing LEDGE levels, resulting in damage to LECs, and cataract formation.