State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou, China.
Clin Rheumatol. 2024 Nov;43(11):3361-3372. doi: 10.1007/s10067-024-07138-5. Epub 2024 Sep 17.
Psoriasis is a chronic inflammatory skin disease. To date, there are no serum biomarkers for psoriasis that have been validated to diagnose or treat psoriasis.
Peptidase inhibitor 3 (PI3) levels in serum were measured using chemiluminescence immunoassay (CLIA) in two independent cohorts including healthy controls (HC) and patients diagnosed with chronic urticaria (CU), chronic eczema (CE), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis vulgaris (PV). Receiver operating characteristic (ROC) curve analysis determined the diagnostic performance of PI3 in patients with psoriasis. The correlation between PI3 levels and the Psoriasis Area Severity Index (PASI) score was analyzed using the Spearman correlation method. Additionally, the study evaluated PI3 expression and treatment response of PV patients 12 weeks before and after topical treatment with calcipotriol betamethasone and calcipotriol ointment (T#1) or topical therapy plus PSORI-CM01 granules (T#2).
In cohort #1, PI3 levels effectively discriminate PV patients from HC and CU patients, with AUCs of 0.909 and 0.840, respectively. In cohort #2, AUCs for detecting PV patients among HC, CU, CE, SLE, and RA patients were 0.940, 0.926, 0.802, 0.989, and 0.951, respectively. For PsA patients, AUCs were 0.989, 0.986, 0.910, 1.000, and 0.984 compared to HC, CU, CE, SLE, and RA patients, respectively. In both cohorts, PI3 levels correlated significantly with PASI scores in PV patients (cohort #1, r = 0.433; cohort #2, r = 0.634) and PsA patients (cohort #2, r = 0.718). Moreover, univariate logistic regression analyses revealed that PV patients with higher PI3 expression had a significantly higher risk of treatment resistance, with an odds ratio of 3.45 [95% confidence interval (CI) 1.54, 7.74, p = 0.003]. Finally, PI3 levels decreased nearly 35-fold more in the responder than in the non-responder group before and after treatment.
Serological PI3 is a reliable biomarker for PV diagnosis and may have the potential to predict and monitor the progression of PV before and after treatment. Key Points • This study validated PI3's diagnostic performance in two independent psoriasis cohorts using CLIA. • PI3 expression is significantly correlated with the psoriasis severity and with patients who benefited from the treatments. • Serological PI3 is a reliable biomarker for psoriasis diagnosis and may have the potential to monitor the psoriasis progression with and without treatments.
银屑病是一种慢性炎症性皮肤病。迄今为止,尚未有经过验证的血清生物标志物可用于诊断或治疗银屑病。
使用化学发光免疫分析(CLIA)在两个独立的队列中测量了肽酶抑制剂 3(PI3)在血清中的水平,这两个队列包括健康对照(HC)和被诊断为慢性荨麻疹(CU)、慢性湿疹(CE)、系统性红斑狼疮(SLE)、类风湿关节炎(RA)、银屑病关节炎(PsA)或寻常型银屑病(PV)的患者。接受者操作特征(ROC)曲线分析确定了 PI3 在银屑病患者中的诊断性能。使用 Spearman 相关性方法分析了 PI3 水平与银屑病面积严重程度指数(PASI)评分之间的相关性。此外,该研究还评估了在接受钙泊三醇倍他米松和钙泊三醇软膏(T#1)或局部治疗加 PSORI-CM01 颗粒(T#2)治疗 12 周前后,PV 患者的 PI3 表达和治疗反应。
在队列#1 中,PI3 水平可有效区分 PV 患者与 HC 和 CU 患者,AUC 分别为 0.909 和 0.840。在队列#2 中,HC、CU、CE、SLE 和 RA 患者中检测 PV 患者的 AUC 分别为 0.940、0.926、0.802、0.989 和 0.951。对于 PsA 患者,与 HC、CU、CE、SLE 和 RA 患者相比,AUC 分别为 0.989、0.986、0.910、1.000 和 0.984。在两个队列中,PI3 水平与 PV 患者(队列#1,r=0.433;队列#2,r=0.634)和 PsA 患者(队列#2,r=0.718)的 PASI 评分均呈显著相关性。此外,单因素 logistic 回归分析显示,PI3 表达较高的 PV 患者治疗抵抗的风险显著增加,优势比为 3.45(95%置信区间 1.54,7.74,p=0.003)。最后,治疗前后,PI3 水平在应答者中下降了近 35 倍,而非应答者中下降了近 35 倍。
血清 PI3 是一种可靠的 PV 诊断生物标志物,可能具有预测和监测治疗前后 PV 进展的潜力。
关键点
·本研究使用 CLIA 在两个独立的银屑病队列中验证了 PI3 的诊断性能。
·PI3 表达与银屑病的严重程度以及对治疗有反应的患者显著相关。
·血清 PI3 是银屑病诊断的可靠生物标志物,具有监测治疗前后银屑病进展的潜力。