HMGB1 Inhibitor Effectively Alleviates Psoriasis-Like Lesions and Inflammatory Cytokines in K14-VEGF Transgenic Mice

Objective:Anti-high-mobility group box 1(HMGB1)is involved in the pathogenesis of many inflammatory and autoimmune diseases,including psoriasis.The present study aimed to investigate the therapeutic effects of HMGB1 monoclonal antibody(mAb)in keratin 14(K14)-vascular endothelial growth factor(VEGF)transgenic homozygous mice.Methods:Twelve VEGF transgenic mice were randomly divided into two groups of six mice each:the anti-HMGB1 mAb group and the immune complex(IC)mAb group.The mice underwent intraperitoneal injection of anti-HMGB1 mAb or IC mAb once every 2 days for a total of three treatments.Compare the lesions on the ears of the mice and evaluate the severity of the lesions using the baseline and clinical scores on the last day of treatment.The changes in psoriasis-like lesions,cellular infiltration of T cells,dendritic cells,and neutrophils were detected by hematoxylin-eosin staining and immunohistochemistry.The mRNA expression of the inflammatory cytokines,including interleukin(IL)-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the lesions were assessed by real-time quantitative polymerase chain reaction.The number ofγδT cells in the lesions of two groups were detected by flow cytometry.Thet test was used to compare their differences.Results:The anti-HMGB1 mAb effectively ameliorated the clinical skin lesions.The clinical scores in the anti-HMGB1 mAb group were lower than those in the IC mAb group(6.00±0.52vs.10.83±0.48,P<0.001).Histopathologic changes and improvements in the K14-VEGF transgenic homozygous mice were evident after three treatments.The scores of mice in the anti-HMGB1 mAb group were significantly lower than those in the IC mAb group(3.25±0.71vs.6.95±0.83,P=0.0033).The average epidermal thickness in the anti-HMGB1 mAb group was reduced by about 45%when compared with that in the IC mAb group(32.15±7.08vs.64.69±7.93,P=0.0054).Moreover,anti-HMGB1 mAb also decreased the number of infiltrating CD3+T cells,myeloperoxidase-positive neutrophils,and CD11c+dendritic cells.The ratio of ear skinγδT cells was reduced in anti-HMGB1 mAb treated group.The mRNA expression of IL-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the anti-HMGB1 mAb group were significantly reduced when compared with IC mAb group(0.36±0.070vs.1.98±0.62,P=0.0148;6.43±1.37vs.13.80±1.33,P=0.0006;2.62±0.83vs.7.77±1.32,P=0.0026;4.69±1.13vs.11.41±1.92,P=0.0054).Conclusion:HMGB1 blockade(anti-HMGB1 mAb)reduced leukocyte infiltration and suppressed inflammatory cytokine expression in this K14-VEGF transgenic mouse model,markedly reducing the severity of the psoriasis-like lesions.HMGB1 blockade might serve as a potential target for the treatment of psoriasis.

Clinical Features of Adult/Adolescent Atopic Dermatitis and Chinese Criteria for Atopic Dermatitis

Background： Atopic dermatitis （AD） is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczemaJAD and to propose Chinese diagnostic criteria for adult/adolescent AD. Methods： A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients （12 years and over） with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and-investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. Results： A total of 2662 valid questionnaires were collected （1369 male and 1293 female）. Of all 2662 patients, 2062 （77.5%） patients had the disease after 12 years old, while only 600 （22.5%） patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine （80.4%） patients had the disease for more than 6 months. One thousand one hundred and forty-four （43.0%） patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight （58.2%） patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. Conclusion： Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis

Background:Psoriasis is a chronic inflammatory skin disease,affecting about 0.6%of the Chinese population.Many patients are not well controlled by conventional treatments,thus there is need for new treatment regimens.In this study,we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.Methods:This study was a 52-week,multicentre,randomized,double-blind,placebo-controlled,parallel-group,Phase 3 trial.A sub-population of study participants(≥18 years)of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab,or placebo.The co-primary endpoints were psoriasis area severity index(PASI)75 and Investigator’s Global Assessment(IGA)0/1 at Week 12.Results:A total of 441 Chinese patients were enrolled in this study.Co-primary outcomes were achieved;300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75(97.7%and 87.2%vs.3.7%,respectively;P<0.001),and IGA 0/1(82.3%and 69.7%vs.2.7%;P<0.001)at Week 12.Treatment efficacy was maintained until Week 52.There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.Conclusion:Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.