Ziolkowska-Banasik Dominika, Pastuszczak Maciej, Zawadzinska-Halat Kamila, Hadas Ewa, Bozek Andrzej
Department of Internal Diseases, Dermatology and Allergology, Medical University of Silesia, 40-055 Katowice, Poland.
Int J Mol Sci. 2025 Jul 3;26(13):6432. doi: 10.3390/ijms26136432.
Identifying immunologic predictors of clinical responses remains an unmet need in the era of biologic therapy for psoriasis. Super responders (SRs), defined as patients achieving complete skin clearance within weeks of treatment initiation, represent an emerging clinical endotype; however, their immunological profiles remain insufficiently characterized. We conducted a prospective observational study to characterize serum cytokine profiles associated with SR status in biologic-naïve patients with moderate-to-severe plaque psoriasis treated with secukinumab, an IL-17A inhibitor. Twenty-eight patients were enrolled and stratified at week 12 into SR (PASI = 0; = 9) and non-super responder (NSR; PASI > 0; = 19) groups. Serum concentrations of 19 cytokines were analyzed at baseline and after 12 weeks of treatment. SRs displayed a distinct immunological signature characterized by significantly higher IL-13 and lower IL-18 baseline levels compared to NSRs ( = 0.002 and = 0.007, respectively), alongside reduced baseline monocyte counts. L1-regularized logistic regression confirmed IL-13 and IL-18 as strong independent predictors of SR status (AUC = 0.91). Moreover, the IL-18/IL-13 ratio emerged as a highly discriminative biomarker ( = 0.00001, AUC = 0.86). Notably, SRs exhibited a more pronounced decline in IL-18 and IL-23 during treatment. Our findings provide novel insights into the immunopathogenesis of super response and suggest that an immunological milieu favoring Th2 polarization may promote superior outcomes with IL-17A blockade. Incorporating IL-13, IL-18, and their ratio into clinical algorithms may facilitate precision-guided biologic therapy in psoriasis.
在银屑病生物治疗时代，确定临床反应的免疫预测指标仍是一项未满足的需求。超级反应者（SRs）被定义为在治疗开始数周内实现皮肤完全清除的患者，代表了一种新出现的临床亚型；然而，他们的免疫特征仍未得到充分描述。我们进行了一项前瞻性观察研究，以描述在使用IL-17A抑制剂司库奇尤单抗治疗的中度至重度斑块状银屑病初治患者中，与SR状态相关的血清细胞因子谱。28例患者入组，并在第12周分层为SR组（银屑病面积和严重程度指数[PASI]=0；n=9）和非超级反应者（NSR；PASI>0；n=19）组。在基线和治疗12周后分析19种细胞因子的血清浓度。与NSR相比，SRs表现出独特的免疫特征，其特征是IL-13基线水平显著更高，IL-18基线水平更低（分别为P=0.002和P=0.007），同时基线单核细胞计数减少。L1正则化逻辑回归证实IL-13和IL-18是SR状态的强独立预测指标（曲线下面积[AUC]=0.91）。此外，IL-18/IL-13比值成为一个高度有鉴别力的生物标志物（P=0.00001，AUC=0.86）。值得注意的是，SRs在治疗期间IL-18和IL-23的下降更为明显。我们的研究结果为超级反应的免疫发病机制提供了新的见解，并表明有利于Th2极化的免疫环境可能促进IL-17A阻断的更好疗效。将IL-13、IL-18及其比值纳入临床算法可能有助于银屑病的精准指导生物治疗。
