Wang Xing, Kaiser Hannah, Kvist-Hansen Amanda, McCauley Benjamin D, Skov Lone, Hansen Peter Riis, Becker Christine
Department of Medicine, Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Cardiology, University Hospital-Herlev and Gentofte, 2900 Hellerup, Denmark.
Int J Mol Sci. 2022 Jan 5;23(1):555. doi: 10.3390/ijms23010555.
Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment and their relationship to CVD. We found that systemically well-treated patients (PASI < 3.0, = 36) had lower circulating levels of IL-17 pathway proteins compared to untreated patients (PASI > 10, = 23). Notably, IL-17C and PI3 were decreased with all four examined systemic treatment types. Furthermore, in patients without CVD, we observed strong correlations among IL-17C/PI3/PASI (r ≥ 0.82, ≤ 1.5 × 10) pairs or between IL-17A/PASI (r = 0.72, = 9.3 × 10). In patients with CVD, the IL-17A/PASI correlation was abolished (r = 0.2, = 0.24) and the other correlations were decreased, e.g., IL-17C/PI3 (r = 0.61, = 4.5 × 10). Patients with moderate-to-severe psoriasis and CVD had lower levels of IL-17A compared to those without CVD (normalized protein expression [NPX] 2.02 vs. 2.55, = 0.013), and lower IL-17A levels (NPX < 2.3) were associated with higher incidence of CVD (OR = 24.5, = 0.0028, 95% CI 2.1-1425.1). As a result, in patients with moderate-to-severe psoriasis, we propose circulating IL-17C and PI3 as potential biomarkers of effective systemic anti-psoriatic treatment, and IL-17A as potential marker of CVD.
银屑病是一种与动脉粥样硬化性心血管疾病（CVD）相关的慢性炎症性疾病。系统性抗银屑病治疗主要包括甲氨蝶呤以及靶向肿瘤坏死因子（TNF）、白细胞介素-12/23（IL-12/23）和白细胞介素-17A（IL-17A）的生物疗法。我们对中重度银屑病患者的血浆蛋白进行了分析，以探索有效全身治疗的潜在生物标志物及其与心血管疾病的关系。我们发现，与未治疗的患者（银屑病面积和严重程度指数 [PASI] > 10，n = 23）相比，系统治疗良好的患者（PASI < 3.0，n = 36）循环中IL-17通路蛋白水平较低。值得注意的是，所有四种检测的全身治疗类型均使IL-17C和PI3降低。此外，在无心血管疾病的患者中，我们观察到IL-17C/PI3/PASI（r≥0.82，p≤1.5×10⁻⁶）各对之间或IL-17A/PASI（r = 0.72，p = 9.3×10⁻⁵）之间存在强相关性。在患有心血管疾病的患者中，IL-17A/PASI相关性消失（r = 0.2，p = 0.24），其他相关性降低，例如IL-17C/PI3（r = 0.61，p = 4.5×10⁻⁴）。与无心血管疾病的患者相比，中重度银屑病合并心血管疾病的患者IL-17A水平较低（标准化蛋白表达 [NPX] 2.02对2.55，p = 0.013），且较低的IL-17A水平（NPX < 2.3）与较高的心血管疾病发病率相关（比值比 [OR] = 24.5，p = 0.0028，95%置信区间2.1 - 1425.1）。因此，在中重度银屑病患者中，我们提出循环中的IL-17C和PI3作为有效全身抗银屑病治疗的潜在生物标志物，而IL-17A作为心血管疾病的潜在标志物。
