Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Nat Commun. 2022 Jun 6;13(1):3140. doi: 10.1038/s41467-022-30615-x.
Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids. An imprecise understanding of the immunologic changes underlying sarcoidosis has limited therapeutic progress. Here in this open-label trial (NCT03910543), 10 patients with cutaneous sarcoidosis are treated with tofacitinib, a Janus kinase inhibitor. The primary outcome is the change in the cutaneous sarcoidosis activity and morphology instrument (CSAMI) activity score after 6 months of treatment. Secondary outcomes included change in internal organ involvement, molecular parameters, and safety. All patients experience improvement in their skin with 6 patients showing a complete response. Improvement in internal organ involvement is also observed. CD4 T cell-derived IFN-γ is identified as a central cytokine mediator of macrophage activation in sarcoidosis. Additional type 1 cytokines produced by distinct cell types, including IL-6, IL-12, IL-15 and GM-CSF, also associate with pathogenesis. Suppression of the activity of these cytokines, especially IFN-γ, correlates with clinical improvement. Our results thus show that tofacitinib treatment is associated with improved sarcoidosis symptoms, and predominantly acts by inhibiting type 1 immunity.
结节病是一种特发性炎症性疾病，通常采用糖皮质激素治疗。由于对结节病潜在免疫变化的认识不明确，限制了治疗进展。在此项开放性标签试验（NCT03910543）中，10 例皮肤结节病患者接受了 JAK 抑制剂托法替布治疗。主要结局是治疗 6 个月后皮肤结节病活动和形态学仪器（CSAMI）活动评分的变化。次要结局包括内部器官受累、分子参数和安全性的变化。所有患者的皮肤均有改善，6 例患者出现完全缓解。还观察到内部器官受累的改善。CD4 T 细胞衍生的 IFN-γ 被鉴定为结节病中巨噬细胞活化的中心细胞因子介质。其他细胞类型产生的额外的 1 型细胞因子，包括 IL-6、IL-12、IL-15 和 GM-CSF，也与发病机制相关。这些细胞因子（尤其是 IFN-γ）活性的抑制与临床改善相关。因此，我们的结果表明托法替布治疗与改善的结节病症状相关，主要通过抑制 1 型免疫起作用。
