银屑病治疗反应的候选生物标志物。

Candidate Biomarkers for Response to Treatment in Psoriatic Disease.

机构信息

R. Offenheim, BSc, O.F. Cruz-Correa, PhD, D. Ganatra, PhD, Psoriatic Arthritis Research Program, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto.

D.D. Gladman, MD, Division of Rheumatology, Faculty of Medicine, University of Toronto, Toronto, Canada.

出版信息

J Rheumatol. 2024 Dec 1;51(12):1176-1186. doi: 10.3899/jrheum.2024-0396.

DOI:10.3899/jrheum.2024-0396

PMID:39218451

Abstract

OBJECTIVE

To determine whether biologic therapy alters serum C-X-C motif chemokine ligand 10 (CXCL10), matrix metalloproteinase 3 (MMP3), S100 calcium-binding protein A8 (S100A8), acid phosphatase 5 (ACP5), and C-C motif chemokine ligand 2 (CCL2) levels in patients with psoriatic arthritis (PsA) and cutaneous psoriasis without arthritis (PsC), and whether baseline levels of these proteins predict response to treatment for PsA.

METHODS

We included (1) patients with PsA taking tumor necrosis factor inhibitors (TNFi), interleukin 17 inhibitors (IL-17i), methotrexate (MTX), and those who were untreated with bDMARDs or csDMARDs; (2) patients with PsC taking bDMARDs; and (3) matched patients with PsC who were not treated with bDMARDs or csDMARDs. Serum samples at baseline and at the 3- to 6-month follow-up visit were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as (1) achieving low disease activity or remission (according to the Disease Activity Index for Psoriatic Arthritis); (2) ≥ 75% reduction in Psoriasis Area and Severity Index; and (3) ≥ 50% reduction in actively inflamed joint count.

RESULTS

In PsA, TNFi reduced serum levels of all 5 proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA ( < 0.05). There were no significant differences between treated or untreated patients with PsC. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (area under the curve > 0.80) for response to biologics in patients with PsA.

CONCLUSION

Treatment with biologics and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in patients with PsA. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.

摘要

目的

确定生物制剂治疗是否会改变银屑病关节炎（PsA）和无关节炎的皮肤银屑病（PsC）患者的血清 C-X-C 基序趋化因子配体 10（CXCL10）、基质金属蛋白酶 3（MMP3）、S100 钙结合蛋白 A8（S100A8）、酸性磷酸酶 5（ACP5）和 C-C 基序趋化因子配体 2（CCL2）水平，以及这些蛋白的基线水平是否可以预测 PsA 的治疗反应。

方法

我们纳入了（1）接受肿瘤坏死因子抑制剂（TNFi）、白细胞介素 17 抑制剂（IL-17i）、甲氨蝶呤（MTX）治疗的 PsA 患者，以及未接受生物 DMARDs 或 csDMARDs 治疗的患者；（2）接受生物 DMARDs 治疗的 PsC 患者；以及（3）未接受生物 DMARDs 或 csDMARDs 治疗的匹配的 PsC 患者。从生物库中检索基线和 3-6 个月随访时的血清样本。使用 Luminex 多重检测法定量蛋白质水平。我们比较了组内随访与基线的蛋白水平以及组间水平的变化。对于生物标志物的预测潜力，我们开发了逻辑回归分类模型。治疗反应定义为（1）达到低疾病活动或缓解（根据银屑病关节炎疾病活动指数）；（2）银屑病面积和严重程度指数减少≥75%；（3）活跃炎症关节计数减少≥50%。

结果

在 PsA 中，TNFi 降低了所有 5 种蛋白的血清水平，IL-17i 增加了 ACP5 和 CCL2，MTX 降低了 MMP3。未治疗的 PsA 与匹配的生物治疗的 PsA 之间 MMP3 和 S100A8 水平的变化有显著差异（<0.05）。接受治疗或未接受治疗的 PsC 患者之间没有显著差异。PsA 患者的 CXCL10、MMP3、S100A8 和 ACP5 的基线水平对生物制剂治疗有良好的预测价值（曲线下面积>0.80）。