Bath-PUVA therapy improves impaired resting regulatory T cells and increases circulating activated regulatory T cells in psoriasis

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Abstracts / Journal of Dermatological Science 84 (2016) e89–e180

and telaprevir, we searched the gene which is induced both by trichloroethylene and telaprevir in normal human keratinocytes. Microarray analysis revealed that the expression of S100 calcium-binding protein A2 gene mRNA (S100A2) is up-regulated by both trichloroethylene and telaprevir in cultured normal human keratinocytes. A real-time PCR analysis confirmed this induction of expression of S100A2 by trichloroethylene and telaprevir in cultured normal human keratinocytes. Immunohistochemical observation revealed that S100A2 protein expression is aberrantly expressed in a spinous layer of the epidermis in severe-type drug eruptions due to telaprevir, while expression of S100A2 is limited in a basal layer of the epidermis in normal subjects. Microarray analysis revealed that the expression of microRNA 132 (miR-132), which binds to S100A2 mRNA, is down-regulated by telaprevir in normal human keratinocytes. Taken together, S100A2 may be a good epidermal marker for toxic systemic drug eruptions and contact dermatitis, while decrease in the expression of miR-132 by telaprevir administration may inversely increase the expression of S100A2 in a spinous layer. http://dx.doi.org/10.1016/j.jdermsci.2016.08.354 P04-09[C12-02] Bath-PUVA therapy improves impaired resting regulatory T cells and increases circulating activated regulatory T cells in psoriasis Ryoji Kubo 1,∗ , Shinnosuke Muramatsu 1 , Yoko Sagawa 1 , Chiyo Saito 1 , Saori Kasuya 1 , Akiko Nishioka 1 , Emi Nishida 1 , Sayuri Yamazaki 2 , Akimichi Morita 1 1 Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 2 Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Bath-PUVA therapy is applied for the treatment of psoriasis due to its efficacy, safety profile, and low cost. The pathogenesis of psoriasis might be an imbalance of Th17 cells and regulatory T cells (Treg). We previously evaluated the effects of bath-PUVA therapy on Th17/Treg balance in peripheral blood obtained from patients with psoriasis. Bath- PUVA therapy significantly reduces the number of Th17 cells. The Treg Functional Ratio (%), defined as %suppression of responder cell proliferation by Treg, is significantly lower in patients (72.1 ± 24.8% n = 15) than in controls (94.4 ± 4.3% n = 9, p = 0.015). The Treg Functional Ratio is significantly increased, and Treg function is restored to almost normal levels. The Treg Functional Ratio is inversely correlated with the Psoriasis Area and Severity Index score (r = −0.407, p = 0.084). These findings confirm that Treg are dysfunctional in psoriasis patients, and that bath-PUVA therapy restores Treg function in most patients. In the present study, we examined three distinct Treg subsets: activated Treg (aTreg), resting Treg (rTreg), and cytokine-secreting non-suppressive Treg (non- Treg). aTreg is considered to have the strongest suppressive activity among the three subsets. We examined these subsets from the peripheral blood before and at each of the 5 sessions of bath-PUVA therapy in 10 psoriasis patients. aTreg levels were significantly increased in the early sessions of bathPUVA therapy and later diminished afterward. The psoriasis lesions improved concomitantly with the increase in aTreg. The improvement was negatively correlated with the Psoriasis Area and Severity

Score. Bath-PUVA therapy resolves the Th17 and Treg imbalance in patients with psoriasis and induces aTreg. http://dx.doi.org/10.1016/j.jdermsci.2016.08.355 P04-10[C02-07] High-incidence of Kaposi’s sarcoma in Miyako Island can be contributed by both high prevalence of HHV8 and male specific susceptibility gene Ryoko Awazawa 1,∗ , Harutaka Katano 2 , Daisuke Utsumi 1 , Kentaro Hayashi 1 , Hiroshi Uezato 1 , Kenzo Takahashi 1 1 Department of Dermatology, University of the Ryukyus, Okinawa, Japan 2 Department of Pathology, National Institute of Infectious Disease, Tokyo, Japan

In Japan, Kaposi’s sarcoma is mostly occurred as a symptom of AIDS, and classic type of Kaposi’s sarcoma is very rare. Indeed, only 79 cases of classic and iatrogenic Kaposi’s sarcoma without AIDS (non-AIDS KS) have been reported over three decades in mainland Japan. However, Okinawa prefecture with a population of 1.39 million is exceptionally endemic area of non-AIDS KS, and 58 cases occurred during a recent 31-year period. Patients ranged from 56 to 93 years old, mean at 77.8-old, and male to female ratio was 2.2–1. It is noteworthy that half of the patients were originate from Miyako Islands with a population of merely 53 thousands, located 300 km southwest of mainland Okinawa. Incidence rate among Miyako Islanders over 50-years old was 4.57/100,000 persons/year, that is roughly 25 and 800 times higher than those of mainland Okinawa and Japan, respectively. To investigate the reason of the high incidence of Kaposi’s sarcoma in Miyako islands, we have carried out the epidemiological survey of human herpes virus 8 (HHV8) infection: the pathogen of Kaposi’s sarcoma. The overall seroprevalence of HHV8 was 15.4% in the Miyako islander, about 11 times higher than those of mainland Okinawa and total Japanese. Meanwhile, the expected incidence of non-AIDS KS in men was about 37 times higher in Miyako Islands than mainland Okinawa, though it was exclusively 9 times in women. The incidence in female Miyako islander can be explainable simply by the high HHV8 infection rate; however, the presence of additional susceptibility factor should be assumed for exceptionally high male incidence. We are now analyzing both virus and host sides’ causality, including the putative HHV8 Miyako variants and the ethnological genomic variants in Miyako natives located at sex chromosomes. http://dx.doi.org/10.1016/j.jdermsci.2016.08.356