Esparza-Díaz José David Tadeo, Gamez-Nava Jorge Ivan, Gonzalez-Lopez Laura, Saldaña-Cruz Ana Miriam, Machado-Sulbaran Andrea Carolina, Beltrán-Ramírez Alberto, Guillén-Medina Miryam Rosario, Flores-Vargas Ana Gabriela, Pérez-Guerrero Edsaúl Emilio
Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Biomedicines. 2024 Jun 25;12(7):1406. doi: 10.3390/biomedicines12071406.
Around 30-60% of patients with rheumatoid arthritis (RA) present treatment failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Chitinase-like proteins (CLPs) (YKL-40, YKL-39, SI-CLP) might play a role, as they are associated with the inflammatory process. This study aimed to evaluate CLP utility as a biomarker in the treatment failure of csDMARDs. A case-control study included 175 RA patients classified into two groups based on therapeutic response according to DAS28-ESR: responders (DAS28 < 3.2); non-responders (DAS28 ≥ 3.2). CLP serum levels were determined by ELISA. Multivariable logistic regression and receiver operating characteristic (ROC) curves were used to evaluate CLPs' utility as biomarkers of treatment failure. Non-responders presented higher levels of YKL-40, YKL-39, and SI-CLP compared with responders (all: < 0.001). YKL-40 correlated positively with YKL-39 (rho = 0.39, < 0.001) and SI-CLP (rho = 0.23, = 0.011) and YKL-39 with SI-CLP (rho = 0.34, < 0.001). The addition of CLPs to the regression models improves diagnostic accuracy (AUC 0.918) compared to models including only clinical classical variables (AUC 0.806) < 0.001. Non-responders were positive for all CLPs in 35.86%. Conclusions: CLPs could be considered as a useful biomarker to assess treatment failure, due to their association with clinical variables and improvement to the performance of regression models.
约30%-60%的类风湿关节炎（RA）患者对传统合成抗风湿药物（csDMARDs）治疗无效。几丁质酶样蛋白（CLPs）（YKL-40、YKL-39、SI-CLP）可能起作用，因为它们与炎症过程相关。本研究旨在评估CLP作为csDMARDs治疗失败生物标志物的效用。一项病例对照研究纳入了175例RA患者，根据DAS28-ESR治疗反应分为两组：反应者（DAS28<3.2）；无反应者（DAS28≥3.2）。通过酶联免疫吸附测定（ELISA）测定CLP血清水平。采用多变量逻辑回归和受试者工作特征（ROC）曲线评估CLP作为治疗失败生物标志物的效用。与反应者相比，无反应者的YKL-40、YKL-39和SI-CLP水平更高（均P<0.001）。YKL-40与YKL-39呈正相关（rho=0.39，P<0.001），与SI-CLP呈正相关（rho=0.23，P=0.011），YKL-39与SI-CLP呈正相关（rho=0.34，P<0.001）。与仅包含临床经典变量的模型（AUC 0.806，P<0.001）相比，将CLP添加到回归模型中可提高诊断准确性（AUC 0.918）。35.86%的无反应者所有CLP均为阳性。结论：由于CLP与临床变量相关且能改善回归模型的性能，可将其视为评估治疗失败的有用生物标志物。
