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Comprehensive study of oral allergy syndrome: Link between patient clinical course and outcome from ISAC analysis
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Abstracts / Journal of Dermatological Science 84 (2016) e1–e88
in cis-UCA treated group by toluidine blue staining. These results may pave a way for a new therapeutic approach for human AD with topical cis-UCA. http://dx.doi.org/10.1016/j.jdermsci.2016.08.203 P10-19 The histamine released from epidermal keratinocytes is involved in ␣-melanocyte-stimulating hormone-induced itching in mice Kyoko Shimizu 1,∗ , Tsugunobu Andoh 2 , Yoko Yoshihisa 1 , Tadamichi Shimizu 1 1 Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan 2 Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Sunburn, wound repair and chronic renal failure with hemodialysis are usually accompanied by both pigmentation and itching in skin. Recent studies have shown that the ␣-melanocytestimulating hormone (␣-MSH) produced from the precursor, proopiomelanocortin, by external stimuli, such as ultraviolet irradiation, is deeply involved in cutaneous pigmentation. However, it is unclear whether ␣-MSH is also involved in the itching resulting from these stimuli. In this study, we investigated whether ␣-MSH elicits itching in male ICR mice. In one part of this study, male mast cell-deficient mice (WBB6F1-W/Wv) and normal littermates (WBB6F1-+/+) were used. An intradermal injection of ␣-MSH into the rostral part of the skin elicited hind-paw scratching, an itch-related behavior, at the injection site. The ␣-MSH-induced scratching was inhibited by treatment with an H1 histamine receptor antagonist, terfenadine. In contrast, the mast cell deficiency did not inhibit the ␣-MSH-induced scratching, suggesting that mast cells do not play a role in ␣-MSH-induced scratching. L-Histidine decarboxylase (HDC) is a key enzyme required for the production of histamine. Immunohistochemical analysis showed HDC was expressed in not only mast cells, but also keratinocytes. These findings indicate that ␣-MSH may play an important role in itching associated with pigmented cutaneous lesions, and that the histamine released from keratinocytes is involved in this ␣-MSHinduced itching. http://dx.doi.org/10.1016/j.jdermsci.2016.08.204 P10-20 Comprehensive study of oral allergy syndrome: Link between patient clinical course and outcome from ISAC analysis Emi Ono ∗ , Chika Matsumura, Saki Matsui, Shun Kitaba, Hiroyuki Murota, Ichiro Katayama Department of Dermatology, University of Osaka, Osaka, Japan Objective: Oral allergy syndrome (OAS) is perhaps the most common food-related allergy in adults. Even of OAS, pollenfood allergy is important for cross-reactivity to proteins. The ImmunoCAP ISAC allows detection of specific IgE to 112 molecular components from 51 allergenic sources. This new approach helps to clarify the molecular bases of primary sensitization and crossreactivity phenomena. We used this approach to analyze allergen
component comprehensively. Subjective: We retrospectively analyzed sera from 11 patients who had been examined based on suspicion of allergy at the Department of Dermatology of the Osaka University. Of the 11 patients, 10 patients have symptom about pruritus, tingling of the lips, oral mucosa, and throat, 1 patients did not have symptom. Methods: ImmunoCAP ISAC was used for screening allergen component and compared with other tests results such as skin prick test, ELISA, western blot and CAP RAST. Result: All subjects had IgE specific for Japanese cedar and cypress. Prevalence ratio of allergy against Bet v1 and PR10 was 63% and 72%, respectively. When compared with patients clinical course and ISAC outcome, there were difference in number of positive components between patients with and without atopic dermatitis. Conclusion: ImmunoCAP ISAC can analyze cross-reactivity to proteins with similar protein structures. ImmunoCAP ISAC may help to clarify natural history of pollen-food allergy and to predict possibility of future symptoms and preventive intervention. http://dx.doi.org/10.1016/j.jdermsci.2016.08.205 P10-21 Intratumoral CD4+ cell depletion sensitizes poorly immunogenic melanomas to immunotherapy with an OX40 agonist Susumu Fujiwara 1,∗ , Hiroshi Nagai 1 , Noriko Shimoura 1 , Shuntaro Oniki 1 , Takayuki Yoshimoto 2 , Chikako Nishigori 1 1 Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan 2 Intractable Disease Research Center, Tokyo Medical University, Tokyo, Japan
OX40 which belongs to the TNF receptor superfamily and is expressed by activated T cells, have potent antitumor activities in preclinical models. However, previous studies have shown that the antitumor effects of OX40 agonists depend on the immunogenicity of the tumor and that poorly immunogenic tumors such as B16F10 melanomas do not respond to OX40 agonist treatment. In this study, we have shown that intratumoral administration of an antiCD4 mAb (for CD4+ cell depletion) sensitized poorly immunogenic B16F10 melanomas to immunotherapy with an OX40 agonist. CD4+ cell depletion markedly enhanced the infiltrations of both CD8+ T cells and natural killer (NK) cells into tumor tissues. Cytokines with antitumor activities, such as IFN-␥, TNF-␣, IL-2, and IL-12, were significantly upregulated by CD4+ cell depletion. However, unexpectedly, the number of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) within tumor tissues also significantly increased as a result of CD4+ cell depletion. As a countermeasure against CD8+ T cell accumulation, CCR2-positive CD11b+Gr-1int (monocytic) MDSCs predominantly increased. Treatment with an OX40 agonist under CD4+ cell depletion neither reduced MDSCs nor increased CD8+ T cells and NK cells, but further enhanced the expression of cytotoxic molecules from tumor-infiltrating effector cells. Our results suggest that combined immunotherapy using both an OX40 agonist and CD4+ cell depletion in situ could be a promising therapeutic strategy for poorly immunogenic tumors and might be more effective if further combined with a therapeutic strategy targeting MDSCs. http://dx.doi.org/10.1016/j.jdermsci.2016.08.206
Abstracts / Journal of Dermatological Science 84 (2016) e1–e88
in cis-UCA treated group by toluidine blue staining. These results may pave a way for a new therapeutic approach for human AD with topical cis-UCA. http://dx.doi.org/10.1016/j.jdermsci.2016.08.203 P10-19 The histamine released from epidermal keratinocytes is involved in ␣-melanocyte-stimulating hormone-induced itching in mice Kyoko Shimizu 1,∗ , Tsugunobu Andoh 2 , Yoko Yoshihisa 1 , Tadamichi Shimizu 1 1 Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan 2 Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Sunburn, wound repair and chronic renal failure with hemodialysis are usually accompanied by both pigmentation and itching in skin. Recent studies have shown that the ␣-melanocytestimulating hormone (␣-MSH) produced from the precursor, proopiomelanocortin, by external stimuli, such as ultraviolet irradiation, is deeply involved in cutaneous pigmentation. However, it is unclear whether ␣-MSH is also involved in the itching resulting from these stimuli. In this study, we investigated whether ␣-MSH elicits itching in male ICR mice. In one part of this study, male mast cell-deficient mice (WBB6F1-W/Wv) and normal littermates (WBB6F1-+/+) were used. An intradermal injection of ␣-MSH into the rostral part of the skin elicited hind-paw scratching, an itch-related behavior, at the injection site. The ␣-MSH-induced scratching was inhibited by treatment with an H1 histamine receptor antagonist, terfenadine. In contrast, the mast cell deficiency did not inhibit the ␣-MSH-induced scratching, suggesting that mast cells do not play a role in ␣-MSH-induced scratching. L-Histidine decarboxylase (HDC) is a key enzyme required for the production of histamine. Immunohistochemical analysis showed HDC was expressed in not only mast cells, but also keratinocytes. These findings indicate that ␣-MSH may play an important role in itching associated with pigmented cutaneous lesions, and that the histamine released from keratinocytes is involved in this ␣-MSHinduced itching. http://dx.doi.org/10.1016/j.jdermsci.2016.08.204 P10-20 Comprehensive study of oral allergy syndrome: Link between patient clinical course and outcome from ISAC analysis Emi Ono ∗ , Chika Matsumura, Saki Matsui, Shun Kitaba, Hiroyuki Murota, Ichiro Katayama Department of Dermatology, University of Osaka, Osaka, Japan Objective: Oral allergy syndrome (OAS) is perhaps the most common food-related allergy in adults. Even of OAS, pollenfood allergy is important for cross-reactivity to proteins. The ImmunoCAP ISAC allows detection of specific IgE to 112 molecular components from 51 allergenic sources. This new approach helps to clarify the molecular bases of primary sensitization and crossreactivity phenomena. We used this approach to analyze allergen
component comprehensively. Subjective: We retrospectively analyzed sera from 11 patients who had been examined based on suspicion of allergy at the Department of Dermatology of the Osaka University. Of the 11 patients, 10 patients have symptom about pruritus, tingling of the lips, oral mucosa, and throat, 1 patients did not have symptom. Methods: ImmunoCAP ISAC was used for screening allergen component and compared with other tests results such as skin prick test, ELISA, western blot and CAP RAST. Result: All subjects had IgE specific for Japanese cedar and cypress. Prevalence ratio of allergy against Bet v1 and PR10 was 63% and 72%, respectively. When compared with patients clinical course and ISAC outcome, there were difference in number of positive components between patients with and without atopic dermatitis. Conclusion: ImmunoCAP ISAC can analyze cross-reactivity to proteins with similar protein structures. ImmunoCAP ISAC may help to clarify natural history of pollen-food allergy and to predict possibility of future symptoms and preventive intervention. http://dx.doi.org/10.1016/j.jdermsci.2016.08.205 P10-21 Intratumoral CD4+ cell depletion sensitizes poorly immunogenic melanomas to immunotherapy with an OX40 agonist Susumu Fujiwara 1,∗ , Hiroshi Nagai 1 , Noriko Shimoura 1 , Shuntaro Oniki 1 , Takayuki Yoshimoto 2 , Chikako Nishigori 1 1 Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan 2 Intractable Disease Research Center, Tokyo Medical University, Tokyo, Japan
OX40 which belongs to the TNF receptor superfamily and is expressed by activated T cells, have potent antitumor activities in preclinical models. However, previous studies have shown that the antitumor effects of OX40 agonists depend on the immunogenicity of the tumor and that poorly immunogenic tumors such as B16F10 melanomas do not respond to OX40 agonist treatment. In this study, we have shown that intratumoral administration of an antiCD4 mAb (for CD4+ cell depletion) sensitized poorly immunogenic B16F10 melanomas to immunotherapy with an OX40 agonist. CD4+ cell depletion markedly enhanced the infiltrations of both CD8+ T cells and natural killer (NK) cells into tumor tissues. Cytokines with antitumor activities, such as IFN-␥, TNF-␣, IL-2, and IL-12, were significantly upregulated by CD4+ cell depletion. However, unexpectedly, the number of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) within tumor tissues also significantly increased as a result of CD4+ cell depletion. As a countermeasure against CD8+ T cell accumulation, CCR2-positive CD11b+Gr-1int (monocytic) MDSCs predominantly increased. Treatment with an OX40 agonist under CD4+ cell depletion neither reduced MDSCs nor increased CD8+ T cells and NK cells, but further enhanced the expression of cytotoxic molecules from tumor-infiltrating effector cells. Our results suggest that combined immunotherapy using both an OX40 agonist and CD4+ cell depletion in situ could be a promising therapeutic strategy for poorly immunogenic tumors and might be more effective if further combined with a therapeutic strategy targeting MDSCs. http://dx.doi.org/10.1016/j.jdermsci.2016.08.206