title: Detection of cytotoxic anti-LEDGF autoantibodies in atopic dermatitis.
abstract: 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 (LEDGF) is a newly isolated survival factor. In the presence of LEDGF, LECs survive well and in the absence of LEDGF, they become highly susceptible to stress. We investigated (1) whether auto-antibody (auto-Ab) to LEDGF is present in sera of AD patients and (2) whether depletion of LEDGF by the auto-Ab kills LECs. In sera from 26 patients with AD using ELISA, we found significantly higher levels of auto-Ab to LEDGF than that in a normal control group. Affinity purified auto-Ab to LEDGF 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 LEDGF, histamine, prostaglandin E2 (PGE2), 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 LEDGF into the privileged compartment, thus, reducing LEDGF levels, resulting in damage to LECs, and cataract formation.
authors.affiliation: Center for Ophthalmic Research, Brigham and Women's Hospital, Department of Ophthalmology, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ayaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohoguro
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Azuma
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Majima
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Yata
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ibaraki
authors.forename: Dhirendra P
authors.initials: DP
authors.lastname: Singh
authors.forename: Vincent
authors.initials: V
authors.lastname: Ko
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Shinohara
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002386:Cataract / Q000097:blood / Q000150:complications / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003876:Dermatitis, Atopic / Q000097:blood / Q000150:complications / Q000276:immunology*; D015232:Dinoprostone / Q000097:blood; D004804:Eosinophils; D004847:Epithelial Cells / Q000276:immunology; D006632:Histamine / Q000097:blood; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D007908:Lens, Crystalline / Q000276:immunology; D051379:Mice
chemical_list: D001323:Autoantibodies; D007136:Immunoglobulins; D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor; D006632:Histamine; D015232:Dinoprostone