Topical skin treatment with Fab fragments of an allergen-specific IgG1 monoclonal antibody suppresses allergen-induced atopic dermatitis-like skin lesions in mice

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• 作者：Chutha Sae-Wong^a ; ^b ; Nobuaki Mizutani^a ; ^{mizutani@kobepharma-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Sureeporn Kangsanant^a ; Shin Yoshino^a
• 关键词：AD ; Atopic Dermatitis ; AUC ; Area under the Response Curve ; H&E ; Hematoxylin and Eosin ; HPF ; High-Power Field ; mAb ; Monoclonal Antibody ; MLNs ; Mandibular Lymph Nodes ; OVA ; Ovalbumin ; OE-1 ; OVA-Specific IgE MAb ; O1-10 ; OVA-Specific IgG1 MAb
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 May 2016
• 年：2016
• 卷：779
• 期：Complete
• 页码：131-137
• 全文大小：7558 K

文摘

Fab fragments (Fabs), which lack effector functions due to the absence of the Fc portion, maintain the ability to bind to specific allergens. In the present study, we examined whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) were able to regulate allergen-induced atopic dermatitis-like skin lesions in mice. BALB/c mice passively sensitized with ovalbumin (OVA)-specific IgE mAb were repeatedly challenged with OVA applied to the skin after sodium dodecyl sulfate treatment. Fabs prepared by the digestion of anti-OVA IgG1 mAb (O1-10) with papain were applied to the skin 30 min before the OVA challenges followed by measurement of clinical symptoms including erythema/hemorrhage, edema, scarring/dryness, and excoriation/erosion of the skin. Treatment with O1-10 Fabs, but not intact O1-10, showed inhibition of clinical symptoms (P<0.01) induced by the repeated OVA challenges in the sensitized mice; O1-10 Fabs suppressed histological changes such as epidermal hyperplasia (P<0.01) and the accumulation of mast cells (P<0.01) and neutrophils (P<0.01). Furthermore, treatment with O1-10 Fabs inhibited the increase in levels of IL-13 (P<0.01) and IL-17A production (P<0.05) in the lymph nodes of the sensitized mice. Additionally, the increased level of OVA in serum following the repeated OVA challenges in the sensitized mice was reduced by the treatment (P<0.05). These results suggest that topical application of pathogenic allergen-specific IgG1 mAb Fabs to the skin of mice is effective in suppressing allergen-induced atopic dermatitis-like skin lesions, suggesting that allergen-specific mAb Fabs could be used as a tool to regulate allergen-induced atopic dermatitis.