血清P-糖蛋白和单体C反应蛋白在大动脉炎中升高。

Serum p-Glycoprotein and Monomeric C-Reactive Protein are Elevated in Takayasu Arteritis.

作者信息

Thakare Darpan Radheshyam, Singh Kritika, Qamar Tooba, Singh Deeksha, Balakrishnan Sandeep, Rathore Upendra, Jain Neeraj, Ora Manish, Misra Durga Prasanna

机构信息

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India.

Department of Clinical Immunology and Rheumatology, King George Medical University (KGMU), Lucknow, Uttar Pradesh, India.

出版信息

J Inflamm Res. 2024 Nov 11;17:8695-8712. doi: 10.2147/JIR.S490958. eCollection 2024.

PURPOSE

Existing biomarkers including C-reactive protein (CRP) do not adequately distinguish active and inactive TAK. We compared serum p-glycoprotein (p-gp)/Multidrug Resistance Protein 1 (MDR1), monomeric CRP (mCRP), CRP, and mCRP:CRP ratio in Takayasu arteritis (TAK) and healthy controls and their relationship with disease activity.

PATIENTS AND METHODS

Serum p-gp mCRP (ELISA) and CRP (nephelometry) were compared between consecutive adults with TAK (>18 years) enrolled from a prospective cohort (n = 92) and healthy controls (n = 29), and between active vs inactive TAK (n = 46 each). In a subset of active immunosuppressive-naïve TAK (n = 29), correlation was assessed between serum p-gp and p-gp expression on circulating T helper lymphocyte populations: overall (CD4+), Th17 (CD4+IL-17+), Th17.1 (CD4+IL-17+IFN-γ+) lymphocytes [normalized to Tregs (CD4+CD25+FoxP3+)]. Changes in serum p-gp, mCRP, CRP, and mCRP:CRP were compared before and after immunosuppression (n = 29). Data was represented using median (Q1-Q3). Receiver operating characteristics (ROC) curves were generated for TAK vs controls, and active vs inactive TAK with serum p-gp, mCRP, CRP, and mCRP:CRP. Multivariable-adjusted linear regression was used to predict active disease with serum p-gp, mCRP, CRP, or mCRP:CRP.

RESULTS

Serum p-gp (11.19 vs 8.05 ng/mL), mCRP (1.61 vs 1.25 µg/L), and CRP (5.40 vs 2.1 mg/L) were elevated in TAK vs controls (p <0.05 for all). CRP was higher and mCRP:CRP ratio was lower in active vs inactive TAK (p < 0.001). ROC curves identified moderate prediction for active disease with CRP and inactive disease with serum p-gp (area under ROC curve 0.705 and 0.392, respectively). Multivariable-adjusted linear regression confirmed association of CRP with active disease (p = 0.009) and serum p-gp with inactive disease (p = 0.041). In treatment-naïve TAK, serum p-gp negatively correlated with p-gp+Th17.1 lymphocytes (Spearman's rho=-0.39, p = 0.046). CRP and serum p-gp were significantly lowered following immunosuppressive therapy in treatment-naïve TAK (p < 0.05).

CONCLUSION

Serum p-gp and mCRP are elevated in TAK. Serum p-gp is associated with inactive disease.

目的

包括C反应蛋白（CRP）在内的现有生物标志物无法充分区分活动期和非活动期的高安动脉炎（TAK）。我们比较了高安动脉炎患者和健康对照者血清中的P-糖蛋白（p-gp）/多药耐药蛋白1（MDR1）、单体CRP（mCRP）、CRP以及mCRP:CRP比值，并研究了它们与疾病活动度的关系。

患者与方法

比较了来自前瞻性队列的连续成年TAK患者（>18岁，n = 92）和健康对照者（n = 29）的血清p-gp、mCRP（酶联免疫吸附测定法）和CRP（散射比浊法），以及活动期与非活动期TAK患者（各n = 46）的上述指标。在一组未接受过免疫抑制治疗的活动期TAK患者（n = 29）中，评估了血清p-gp与循环T辅助淋巴细胞群体（总体（CD4+）、Th17（CD4+IL-17+）、Th17.1（CD4+IL-17+IFN-γ+）淋巴细胞[以调节性T细胞（CD4+CD25+FoxP3+）为参照进行标准化]）上p-gp表达之间的相关性。比较了免疫抑制治疗前后（n = 29）血清p-gp、mCRP、CRP和mCRP:CRP的变化。数据以中位数（Q1-Q3）表示。绘制了TAK与对照者、活动期与非活动期TAK患者的血清p-gp、mCRP、CRP和mCRP:CRP的受试者工作特征（ROC）曲线。采用多变量调整线性回归分析，以血清p-gp、mCRP、CRP或mCRP:CRP预测活动期疾病。

结果

与对照者相比，TAK患者的血清p-gp（11.19 vs 8.05 ng/mL）、mCRP（1.61 vs 1.25 μg/L）和CRP（5.40 vs 2.1 mg/L）均升高（所有p < 0.05）。与非活动期TAK相比，活动期TAK的CRP更高，mCRP:CRP比值更低（p < 0.001）。ROC曲线显示，CRP对活动期疾病有中度预测价值，血清p-gp对非活动期疾病有中度预测价值（ROC曲线下面积分别为0.705和0.392）。多变量调整线性回归证实CRP与活动期疾病相关（p = 0.009），血清p-gp与非活动期疾病相关（p = 0.041）。在未接受过治疗的TAK患者中，血清p-gp与p-gp+Th17.1淋巴细胞呈负相关（斯皮尔曼等级相关系数=-0.39，p = 0.046）。在未接受过治疗的TAK患者中，免疫抑制治疗后CRP和血清p-gp显著降低（p < 0.05）。