血清肿瘤标志物对类风湿性关节炎相关间质性肺病的诊断价值研究

Diagnostic value of serum tumor markers for rheumatoid arthritis-associated interstitial lung disease

摘要:

目的 检测血清肿瘤标志物在类风湿性关节炎（RA）患者中的表达，探讨相关肿瘤标志物对类风湿性关节炎并发间质性肺病（RA-ILD）的诊断价值。方法 回顾性分析2021年1月—2023年4月在安徽中医药大学第一附属医院风湿科住院的101例RA患者的病历资料。根据高分辨率CT（HRCT）确诊RA-ILD患者31例（RA-ILD组），类风湿性关节炎不伴间质性肺病（RA-non-ILD）患者70例（RA-non-ILD组）。收集两组患者的病历资料及抗环瓜氨酸肽抗体（anti-CCP）、类风湿因子（RF）、C反应蛋白（CRP）、血细胞沉降率（ESR）等实验室检测数据。采用化学发光法检测甲胎蛋白（AFP）、癌胚抗原（CEA）、糖类抗原125（CA125）、糖类抗原153（CA15-3）、糖类抗原199（CA199）、细胞角蛋白-19片段（CA21-1）和人附睾蛋白4（HE4）的表达。结果 RA-ILD组血清RF、CRP、ESR水平均高于RA-non-ILD组（P <0.05）。RA-ILD组血清CA125、HE4水平均高于RA-non-ILD组（P <0.05）。< 50岁、50～< 60岁、≥ 60岁RA-non-ILD患者血清HE4水平比较，差异无统计学意义（P >0.05）。全年龄段（35～72岁）RA-ILD组HE4水平高于≥ 60岁RA-non-ILD组（P <0.05）。受试者工作特征曲线分析结果显示，HE4、CA125、RF、CRP、ESR诊断RA-ILD的最佳截断值分别为42.45 pmol/L、19.85 u/mL、112.00 KIU/L、18.23 mg/L和54.50 mm/h，曲线下面积（AUC）分别为0.817、0.672、0.668、0.676和0.729，敏感性分别为80.00%、38.71%、64.52%、58.06%和58.06%，特异性分别为74.29%、94.29%、67.14%、77.14%和85.71%。本研究将HE4、CA125分别与RF、CRP、ESR进行联合诊断时发现，HE4与RF、CRP、ESR联合诊断时的AUC为0.874，敏感性和特异性分别为84.29%和80.65%；CA125与RF、CRP、ESR联合诊断时的AUC为0.752，敏感性和特异性分别为74.29%和58.06%。结论 血清肿瘤标志物中HE4对RA-ILD的诊断效能最佳，且与RA活动性指标联合诊断RA-ILD具有良好的临床应用价值。

Abstract:

Objective To detect the serum levels of tumor markers in patients with rheumatoid arthritis (RA), and to explore the diagnostic value of serum tumor markers for RA-associated interstitial lung disease (RA-ILD).Methods We retrospectively analyzed the medical records of 101 patients with RA hospitalized in the Department of Rheumatology of our hospital from January 2021 to April 2023, with 31 patients with RA-ILD diagnosed based on high-resolution CT (HRCT) (RA-ILD group) and 70 RA patients without ILD (RA-non-ILD group). The clinical data and laboratory test data including anti-cyclic citrullinated peptide antibody (anti-CCP antibody), rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) of the two groups of patients were collected. The expressions of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 199 (CA-199), cytokeratin-19 fragment (CA21-1) and human epididymis protein 4 (HE4) were detected by chemiluminescent immunoassay.Results The levels of RF, CRP, and ESR in the RA-ILD group were higher than those in the RA-non-ILD group (P < 0.05). The levels of HE4 and CA125 in the RA-ILD group were higher than those in the RA-non-ILD group (P < 0.05). There was no difference in the serum level of HE4 among patients in the RA-non-ILD group aged < 50 years, aged 50 to < 60 years, and aged ≥ 60 years (P > 0.05). The levels of HE4 in patients of the RA-ILD group across the entire age range (35 to 72 years old) were higher than those of the RA-non-ILD group aged ≥ 60 years (P < 0.05). The ROC curve analysis showed that optimal cut-off values of HE4, CA125, RF, CRP and ESR for diagnosing RA-ILD were 42.45 pmol/L, 19.85 u/mL, 112.00 KIU/L, 18.23 mg/L, 54.50 mm/h, with the areas under the ROC curves (AUCs) being 0.817, 0.672, 0.668, 0.676, and 0.729, the sensitivities being 80.00%, 38.71%, 64.52%, 58.06%, and 58.06%, and the specificities being 74.29%, 94.29%, 67.14%, 77.14%, and 85.71%, respectively. We combined HE4 or CA125 with RF, CRP, and ESR for diagnosis and found that the combined detection of HE4, RF, CRP, and ESR yielded an AUC of 0.874, with the sensitivity and specificity being 84.29% and 80.65%, respectively, and that the combined detection of CA125, RF, CRP, and ESR yielded an AUC of 0.752, with the sensitivity and specificity being 74.29% and 58.06%, respectively.Conclusion Among the serum tumor markers, HE4 has the best diagnostic efficacy for RA-ILD, and its combination with activity indicators of RA holds significant clinical value for the diagnosis of RA-ILD.