白细胞介素-4、C-反应蛋白与特应性皮炎及度普利尤单抗治疗效果的关系^*

The Relationship Between Interleukin-4, C-reactive Protein, Atopic Dermatitis, and the Therapeutic Effect of Dupilumab

摘要

目的 分析白细胞介素（interleukin, IL）-4、C-反应蛋白（C-reactive protein, CRP）与特应性皮炎发病、病情严重程度及度普利尤单抗治疗疗效的关系。方法 回顾性选取2022年2月–2023年11月就诊的106例特应性皮炎患者作为研究组，另选同期健康志愿者50例作为对照组，检测研究组不同分期（急性期、亚急性期、慢性期）、不同病情严重程度（轻、中、重）与对照组的IL-4、CRP水平，使用受试者工作特征（receiver operating characteristic，ROC）曲线分析IL-4、CRP对特应性皮炎的诊断价值。使用Spearman分析特应性皮炎患者病情严重程度与IL-4、CRP水平的关系。所有特应性皮炎患者均接受规范16周的度普利尤单抗治疗，分为治疗有效组与治疗无效组，比较患者治疗前及治疗4周、8周、12周、16周的IL-4、CRP水平变化，分析治疗后各时间点的IL-4、CRP与疗效的相关性。结果 IL-4、CRP水平均为慢性期<亚急性期<急性期（P<0.05），轻度组<中度组<重度组（P<0.05）；治疗前研究组IL-4、CRP水平分别为（14.88±3.91） pg/mL、（6.07±3.02） mg/L，高于对照组的（8.27±1.09） pg/mL、（1.06±0.31） mg/L，差异有统计学意义（P<0.05）。IL-4、CRP及二者联合诊断特应性皮炎的曲线下面积分别为0.831〔95%置信区间（confidence interval, CI）：0.763～0.886〕、0.776（95%CI：0.702～0.839）、0.882（95%CI：0.821～0.928）（P<0.05）；Spearman分析显示，特应性皮炎患者IL-4、CRP水平与病情严重程度均呈正相关（r=0.643、0.659，P<0.05）；随着治疗时间的增加，IL-4、CRP水平逐渐降低，有效组与治疗无效组间差异有统计学意义（P<0.05）；治疗有效组患者治疗前后各时点的IL-4、CRP水平均低于治疗无效组同期（P<0.05）；Spearman分析显示，特应性皮炎患者IL-4、CRP水平与治疗12周（r=0.267、0.280，P<0.05）、治疗16周的疗效均呈正相关（r=0.214、0.377，P<0.05）。结论 IL-4、CRP与特应性皮炎的发生、发展存在相关性，度普利尤单抗治疗后患者IL-4、CRP水平显著下降，且IL-4、CRP在特应性皮炎诊断中具有一定价值。

Abstract

Objective To analyze the relationship between interleukin-4 (IL-4), C-reactive protein (CRP), and the incidence, severity, and therapeutic efficacy of Dupilumab in atopic dermatitis. Methods A total of 106 patients with atopic dermatitis treated from February 2022 to November 2023 were retrospectively selected as the study group, and 50 healthy volunteers from the same period were selected as the control group. The levels of IL-4 and CRP were measured at different stages (acute, subacute, chronic) and severities (mild, moderate, severe) in both the study and control groups. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of IL-4 and CRP in atopic dermatitis. Spearman analysis was used to assess the relationship between the severity of atopic dermatitis and the levels of IL-4 and CRP in patients. All patients with atopic dermatitis received standardized 16-week treatment with pembrolizumab and were divided into effective and ineffective treatment groups. Changes in IL-4 and CRP levels before treatment and at 4, 8, 12, and 16 weeks of treatment were compared, and the correlation between IL-4, CRP, and treatment efficacy at each time point after treatment was analyzed. Results The levels of IL-4 and CRP were lowest in the chronic phase, higher in the subacute phase, and highest in the acute phase (P < 0.05), with the mild group showing lower levels than the moderate group, and the moderate group lower than the severe group ( P < 0.05). Before treatment, the levels of IL-4 and CRP in the study group were (14.88 ± 3.91) pg/mL and (6.07 ± 3.02) mg/L, respectively, both significantly higher than those in the control group, which were (8.27 ± 1.09) pg/mL and (1.06 ± 0.31) mg/L ( P < 0.05). The areas under the curve for IL-4, CRP, and their combined diagnosis of atopic dermatitis were 0.831 (95% CI: 0.763-0.886), 0.776 (95% CI: 0.702-0.839), and 0.882 (95% CI: 0.821-0.928), respectively ( P < 0.05). Spearman analysis showed that IL-4 and CRP levels in patients with atopic dermatitis were positively correlated with disease severity ( r = 0.643, 0.659, P < 0.05). As treatment time increased, IL-4 and CRP levels gradually decreased, with a statistically significant difference between the effective and ineffective groups ( P < 0.05). At all time points before and after treatment, IL-4 and CRP levels in the effective treatment group were lower than those in the ineffective treatment group ( P < 0.05). Spearman analysis also showed that IL-4 and CRP levels in patients with atopic dermatitis were positively correlated with treatment efficacy at 12 weeks ( r = 0.267, 0.280, P < 0.05) and 16 weeks ( r = 0.214, 0.377, P < 0.05). Conclusion IL-4 and CRP are correlated to the occurrence and development of atopic dermatitis. After treatment with Dupilumab, the levels of IL-4 and CRP in patients significantly decreased. IL-4 and CRP have diagnostic value for atopic dermatitis.

关键词

白细胞介素-4 / C-反应蛋白 / 特应性皮炎 / 度普利尤单抗治疗 / 临床疗效

Key words

Interleukin-4 / C-reactive protein / Atopic dermatitis / Dupilumab treatment / Clinical curative effect

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基金资助

*邢台市重点研发计划自筹项目(2022ZC178)