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 (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.
Ayaki
Masahiko
M
Center for Ophthalmic Research, Brigham and Women's Hospital, Department of Ophthalmology, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
Ohoguro
Nobuyuki
N
Azuma
Noriyuki
N
Majima
Yoshinao
Y
Yata
Kiyomi
K
Ibaraki
Nobuhiro
N
Singh
Dhirendra P
DP
Ko
Vincent
V
Shinohara
Toshimichi
T
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
D001323:Autoantibodies; D007136:Immunoglobulins; D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor; D006632:Histamine; D015232:Dinoprostone