Br J Dermatol:Brodaluma阻断 IL-17RA可减少化脓性汗腺炎皮肤和血清中的炎症通路

2022-03-09 医路坦克 MedSci原创

化脓性汗腺炎(HS)是一种复杂的炎症性皮肤病,本文研究Brodaluma在HS皮肤和血清中的分子反应特征,并确定治疗反应的生物标志物。

化脓性汗腺炎(HS)是一种复杂的炎症性皮肤病,伴有疼痛的结节和脓肿,并发展为恶臭的引流隧道。与其他全身性皮肤病相比,HS具有显着的疾病负担,对患者的生活质量影响更为深远。有效的治疗方法仍然有限,TNF抑制剂阿达木单抗是美国食品药品管理局(FDA)批准的唯一一种用于该疾病的生物制剂,但仅达到42-59%的临床反应(HiSCR)反应。尽管过去几年的研究进展不断增加,但由于我们对HS5的分子发病机制的了解相对不完整,新疗法的发现和开发仍然受到阻碍。疾病的形态异质性(包括结节、脓肿、隧道和纤维化区域),以及在治疗研究中评估分子反应(即,哪些区域需要活检)方面缺乏标准化共识,增加了HS研究的挑战。此外,疾病活动性的分子和细胞生物标记物在HS中仍然难以捉摸。一项研究发现,在阿达木单抗治疗后,HS皮损活检组织中转录B细胞签名明显减少,B细胞趋化因子CXCL13减少,而另一项研究发现辅助性T细胞(Th)17细胞的频率降低。然而,其他关于apremilast和ustekinumab的研究没有发现治疗反应的生物标记物,尽管临床有效。

最近的工作发现在HS 11-18 19中IL-17A和IL-17C的表达增加,Th17细胞浸润增多。考虑到IL-17信号在疾病发病机制中的作用的证据,我们在本研究中探索了在HS中IL-17A通路的治疗靶点。最近一项针对IL-17A和IL-17F的单克隆抗体Bimekizumab的II期双盲安慰剂对照随机试验也显示出疗效,46%的接受治疗的患者在12周和24周达到HISCR75。考虑到HS中IL-17A/C水平的升高,靶向IL-17受体A(IL-17RA)(受体复合体的一个共有亚单位)是另一个有吸引力的治疗途径。我们最近在HS中进行了一项针对IL-17RA的人源性单克隆抗体Brodalab的临床研究,并报告了令人振奋的临床结果,100%的参与者达到了HiScR31-34。没有2/3级的不良事件,治疗耐受性良好,尽管之前有克罗恩病恶化和与感染发展有关的报道)

     在这里,我们用一种途径的方法来研究IL-17RA拮抗在HS中的分子影响。这是第一项在治疗干预的背景下系统比较皮损、皮损周围和非皮损HS皮肤治疗反应的研究。

     10名参与者在0周、1周、2周、4周和每隔2周皮下注射210 mg/1.5ml Brodalumab,纳入这项分子图谱研究(NCT03960268)。评估非皮损、皮损周围和皮损HS皮肤活检的RNA测序和免疫组织化学,以及基线、4周和12周血清的Olink高通量蛋白质组学。

     在第12周,Brodalumab导致总体炎症减轻,并改善了银屑病、角质形成细胞和中性粒细胞相关的途径。尽管皮损周围和皮损皮肤在基线上没有差异表达的基因,但对皮损周围皮肤的治疗反应进行了最好的评估。在血清中,Brodalumab治疗减少了涉及中性粒细胞炎症的途径。在第12周,皮肤中性粒细胞相关脂钙蛋白-2(Lcn2)和血清IL-17A的基线表达较高的患者在皮肤活检中显示出与HS相关的炎性细胞因子的下降幅度更大。

     综上所述,Brodalumab可以抑制IL-17RA影响HS中的几种致病性炎症轴。Perilesional可以提供有效和强大的治疗反应评估。LCN2在皮肤中的表达和血清中的IL-17A可以用作生物标志物来筛选可能对brodalumab具有良好治疗反应的患者。

文献来源:Navrazhina K,  Frew JW,  Grand D, IL-17RA blockade by brodalumab decreases inflammatory pathways in hidradenitis suppurativa skin and serum.Br J Dermatol 2022 Feb 22;

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    2022-03-09 医鸣惊人

    认真学习了

    0

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    2022-03-06 fzwish20000
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    2022-03-06 jjjiang0202

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Eur J Dermatol:强脉冲光或是治疗轻中度化脓性汗腺炎的一种有效疗法

化脓性汗腺炎(HS)是一种皮肤间质的慢性炎症性疾病。HS影响毛囊,造成毛囊周围炎症,形成结节和疼痛的脓肿。强脉冲光(IPL)采用选择性的光热作用来破坏毛囊。发表于Eur J Dermatol的一项单盲

Br J Dermatol:化脓性汗腺炎中一个独特的促炎因子——IL-36

背景:白细胞介素(IL)- 36家族可能参与炎症性疾病的治疗。大汗腺感染后在皮内和皮下组织反复发作,广泛蔓延,形成范围较广的慢性炎症、小脓肿、复杂性窦道和瘘管,称为化脓性汗腺炎(suppurative hidrosadenitis)。发病部位多在大汗腺分布区,如腑下、肛门、生殖器、臀部、股部、腹股沟、乳晕、脐部和外耳道,发生于肛门周围者称为肛周化脓性汗腺炎。在中医学中属蜂窝漏、串臀瘘的范畴。20~