Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis
Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis
复制标题
DOI：
10.1172/jci.insight.139930
复制
发表时间：
2020-10-02
期刊：
影响因子：
8
通讯作者：
Prens, Errol P.
中科院分区：
文献类型：
--
作者：
Gudjonsson, Johann E.;Tsoi, Lam C.;Prens, Errol P.
化脓性汗腺炎（HS）是一种使人衰弱的慢性炎症性皮肤病，其特征是慢性脓肿形成和腹股沟、腋窝和会阴部多个引流窦道的发展。使用蛋白质组学和转录组学方法，我们深入表征了HS中的炎症反应，揭示了以IFN-γ、IL-36和TNF为中心的免疫反应，IL-17 A的贡献较小。我们进一步确定了B细胞和浆细胞，以及相关的免疫球蛋白产生和补体激活的增加，作为HS发病机制的关键参与者，其中布鲁顿酪氨酸激酶（BTK）和脾酪氨酸激酶（SYK）途径激活作为HS中的中心信号转导网络。这些数据提供了临床前证据，可加速针对中重度HS中BTK和SYK信号传导的临床试验。
Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-gamma, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton's tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS.