Pemphigus vulgaris autoimmune globulin induces Src-dependent tyrosine-phosphorylation of plakophilin 3 and its detachment from desmoglein 3

Abstract

The cell adhesion molecule plakophilin 3 (Pkp3) plays an essential role in the maintenance of skin integrity and is targeted in certain autoimmune conditions. In one example, we have shown that Pkp3 is instrumental in mediating the discohesive effects of sera from patients with pemphigus vulgaris (PV), a life-threatening autoimmune disease that targets intercellular adhesion in the epidermis. In the present study, we determine the effect of PV autoimmune globulin (PV IgG) on Pkp3 in an in-vitro model of PV. We demonstrate that Pkp3 becomes tyrosine phosphorylated as early as 30?min upon binding of PV IgG to keratinocyte surface and eventually detaches from its binding partner desmoglein 3 (Dsg3). In parallel, Pkp3 is depleted from the membrane (Triton X-soluble) fraction and accumulates in the cytoplasm within 240?min of incubation with PV IgG. Inhibition of Pkp3 phosphorylation by a Src inhibitor attenuates the discohesive effects of PV IgG. Taken together, the data demonstrate that activation of Src-kinase signalling is crucial for PV acantholysis and acts, at least in part, via phosphorylation of the adaptor protein Pkp3.     

寻常型银屑病患者血清IL-22水平与治疗转归的关系

目的：探究寻常型银屑病患者血清IL-22水平与治疗转归的关系。方法选取寻常型银屑病患者240例,设为观察组,选取健康人240例,设为对照组。用酶联免疫吸附法（ELISA）检测对照组患者,以及观察组治疗前与治疗后2周、4周及6周血清中的IL-22水平;评估观察组患者的疾病严重程度指数（PASI）。应用Pearson直线相关分析对观察组治疗期间IL-22水平与PASI评分进行相关性分析。结果观察组在治疗前血清中IL-22水平显著高于对照组（P＜0.05）,观察组治疗后血清中IL-22水平显著低于治疗前（P＜0.05）。应用Pearson直线相关分析显示血清IL-22水平与PASI评分呈正相关关系（r=0.832,P=0.001）。结论寻常型银屑病患者体内血清IL-22水平与疾病进展程度和预后转归相关性。     

克银合剂治疗血热型白疕疗效及对肿瘤坏死因子-α的影响

目的 研究克银合剂治疗血热型白疕(寻常型银屑病)疗效及对肿瘤坏死因子-α(TNF-α)的影响.方法 选取30例寻常型银屑病血热型患者作为研究对象,进行克银合剂治疗,另选取同期接受健康体检的健康人30例作为对照组,研究克银合剂对TNF-α的影响.结果 治疗前TNF-α水平显著高于健康对照组,进行克银合剂治疗后患者症状、体征评分均显著低于治疗前,各项指标水平已经接近对照组.结论 克银合剂能改善寻常型银屑病血热型患者的临床症状,对TNF-α异常也有一定的改善作用.     

Treatment of verruca vulgaris with topical cidofovir in an immunocompromised patient: a case report and review of the literature

Lesions caused by verrucus vulgaris are commonly refractory to therapy and may become large, painful, or disfiguring in immunocompromised patients. Cidofovir is a potent nucleoside analog antiviral agent shown to have in vitro and in vivo activity against a broad spectrum of DNA viruses. We report a successful use of topical cidofovir to treat verruca vulgaris lesions in a highly immunocompromised patient, who was not considered a candidate for conventional therapy.     

Mechanisms of synergy of autoantibodies to M3 muscarinic acetylcholine receptor and secretory pathway Ca2+/Mn2+-ATPase isoform 1 in patients with non-desmoglein pemphigus vulgaris

Pemphigus vulgaris (PV) is a potentially lethal mucocutaneous blistering disease characterized by IgG autoantibodies (AuAbs) binding to epidermal keratinocytes and inducing a devastating blistering disease affecting oral and/or esophageal surfaces and, sometimes, also the skin. Anti-keratinocyte AuAbs developed by the desmoglein (Dsg) 1/3 AuAb-negative acute PV patients are pathogenic, as they induced acantholysis and epidermal split in the experimental models of PV in vitro and in vivo. These PV patients have various combinations of AuAbs to keratinocyte muscarinic acetylcholine receptor subtype M3 (M3AR), the secretory pathway Ca²⁺/Mn²⁺-ATPase isoform 1 (SPCA1), and desmocollin 3 whose relative concentrations correlate with the disease activity. In this study, we identified new molecular mechanisms of the synergistic cooperation of AuAbs to M3AR and SPCA1 in inducing acantholysis in the anti-Dsg 1/3 AuAb-negative PV patients. Anti-M3AR AuAb was found to play an important role in determining the level of intraepidermal split just above the basal cells, caspase to mediate early pro-apoptotic events triggered by anti-SPCA1 AuAb, and the neonatal Fc receptor (FcRn) to contribute to the pathobiological actions of both anti-M3AR and anti-SPCA1 AuAbs. Altogether, these novel results support our original hypothesis that pemphigus acantholysis is a complex disease process (also known as apoptolysis) initiated by AuAbs directed against different keratinocyte proteins that play important roles in supporting cell viability and regulating vital cell functions.     

ANTI-ALLERGIC EFFECTS OF SANGUISORBA OFFICINALIS ON ANIMAL MODELS OF ALLERGIC REACTIONS

ABSTRACT

We investigated the effect of aqueous extract of Sanguisorba officinalis L.(Rosaceae) root (SOAE) on the immediate-type allergic reactions in vivo and in vitro. SOAE (0.01 to 1 g/kg) inhibited systemic allergic reaction induced by compound 48/80. When SOAE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. SOAE (0.001 to 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE. SOAE (0.001 to 1 mg/mL) also dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP (cAMP) in RPMC, When SOAE was added, significantly increased compared with that of normal control. Moreover, SOAE (0.01 to 1 mg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-α (TNF-α) production. These results suggest that SOAE may be beneficial in the regulation of immediate-type allergic reaction.     

415 nm蓝光联合5%过氧苯甲酰凝胶治疗轻中度寻常性痤疮的疗效

 目的 观察415 nm蓝光联合5%过氧苯甲酰凝胶治疗轻中度寻常性痤疮的临床疗效与安全性。方法 选取武警湖北总队医院2019-03至2020-09轻中度寻常性痤疮90例,随机分为3组,每组30例。联合组同时予415 nm蓝光照射联合5%过氧苯甲酰凝胶外用;蓝光组和药物组分别予415 nm蓝光照射和5%过氧苯甲酰凝胶外用。3组均在治疗8周后判定疗效。结果 治疗8周后联合组有效率为83.3％。蓝光组和药物组有效率分别为30％和56.7％,与联合组有效率比较,差异均有统计学意义。治疗过程中不良反应少见且患者均可耐受。结论 415 nm蓝光联合5%过氧苯甲酰凝胶治疗轻中度寻常性痤疮疗效显著,不良反应少。     

艾拉光动力联合咪喹莫特乳膏治疗扁平疣的疗效

目的：观察艾拉光动力联合5%咪喹莫特乳膏治疗扁平疣的临床疗效。方法选取2010年5月至2014年10月收治的81例扁平疣患者,随机分为观察组41例与对照组40例。对照组患者仅给予5-氨基酮戊酸光动力疗法,而观察组患者在光动力治疗基础上再于患处涂抹5%咪喹莫特乳膏8周。治疗结束后连续3个月观察两组患者的临床疗效与复发情况并比较分析。结果观察组患者的总有效率为100.00%,高于对照组的92.50%,两组差异无统计学意义（ P ﹥0.05）;②观察组患者复发率为5.26%,而对照组患者复发率为28.57%,两组比较差异有统计学意义（P ﹤0.05）。结论艾拉光动力联合5%咪喹莫特乳膏治疗扁平疣可以有效提高临床疗效,降低复发率。