RA伴肺间质病变患者血清KL-6水平及与T淋巴细胞亚群的关系

Serum KL-6 Level and Its Relationship with T Lymphocyte Subsets in RA Patients with Interstitial Lung Disease

目的:探究类风湿关节炎(RA)伴肺间质病变(ILD)患者血清涎液化糖链抗原-6(KL-6)水平及与T淋巴细胞亚群的关系。方法:选取2020年9月至2021年9月我院RA伴ILD患者75例,作为研究组,根据1∶1匹配病例对照原则选取同期单纯RA患者75例,作为对照组。比较两组一般资料,酶联免疫吸附法检测血清KL-6水平、流式细胞仪检测T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+))、采用28处关节疾病活动度(Disease activity score 28,DSA 28)评估RA活动度,并比较研究组不同肺通气障碍程度、肺弥散功能障碍程度患者血清KL-6水平,分析研究组血清KL-6水平与T淋巴细胞亚群、RA活动度、肺通气障碍程度、肺弥散功能障碍程度的相关性。研究组患者均行对症治疗,治疗6个月后评估疗效情况,比较不同疗效患者治疗前、治疗1个月、3个月、6个月血清KL-6水平,通过受试者工作特征(ROC)曲线评价血清KL-6预测疗效的价值。结果:研究组血清KL-6水平、DSA 28评分均高于对照组,(819.65±85.34 vs 418.93±52.67,t=34.605,P<0.001;3.46±0.85 vs 2.59±0.77,t=6.569,P<0.001),CD3^(+)、CD4^(+)、CD8^(+)水平低于对照组(41.69±5.39 vs 44.86±5.72,t=3.493,P=0.001;17.82±3.24 vs 23.69±3.86,t=10.087,P<0.001;18.05±2.81 vs 25.73±3.42,t=15.026,P<0.001);肺通气障碍、肺弥散功能障碍重度患者血清KL-6水平均高于中度、轻度患者,中度患者血清KL-6水平均高于轻度患者(P<0.05);研究组血清KL-6水平与CD4^(+)、CD8^(+)水平呈负相关(r=-0.526,P<0.001,r=-0.713,P<0.001),与DSA 28评分、肺通气障碍程度、肺弥散功能障碍程度呈正相关(r=0.429,P<0.001,r=0.802,P<0.001,r=0.851,P<0.001);疗效不良患者治疗前、治疗1个月、3个月、6个月血清KL-6水平均高于疗效良好患者(P<0.05);治疗前血清KL-6水平预测RA伴ILD患者疗效为不良的曲线下面积(AUC)为0.838,预测敏感度、特异度分别为75.02%、88.14%。结论:RA伴ILD患者血清KL-6水平明显升高,其水平与T淋巴细胞亚群异常密切相关,且能辅助临床评估患者病情及预测疗效,具有较高应用价值。

Objective:To investigate the serum salivary liquefied carbohydrate antigen-6(KL-6)level and its relationship with T lymphocyte subsets in patients with rheumatoid arthritis(RA)with interstitial lung disease(ILD).Methods:Seventy-five patients with RA with ILD in our hospital from September 2020 to September 2021 were selected as the study group,and 75 patients with RA alone in the same period were selected as the control group according to the 1∶1 matching case-control principle.The general data of the two groups were compared,the serum KL-6 level was detected by enzyme-linked immunosorbent assay,the T lymphocyte subsets(CD3^(+),CD4^(+),CD8^(+))were detected by flow cytometry,and RA activity was assessed using the Disease activity score 28(DSA 28),and the patients with different degrees of pulmonary ventilation disturbance and pulmonary diffusion dysfunction in the study group were compared.Serum KL-6 level,and the correlation between serum KL-6 level and T lymphocyte subsets,RA activity,degree of pulmonary ventilation disturbance,and degree of pulmonary diffusion dysfunction in the study group were analyzed.All patients in the study group received symptomatic treatment,and the curative effect was evaluated after 6 months of treatment.The serum KL-6 levels before treatment,1 month,3 months,and 6 months of treatment in patients with different curative effects were compared,and the value of serum KL-6 in predicting curative effect was evaluated by receiver operating characteristic(ROC)curve.Results:The serum KL-6 level and DSA 28 score of the study group were higher than those of the control group(819.65±85.34 vs 418.93±52.67,t=34.605,P<0.001;3.46±0.85 vs 2.59±0.77,t=6.569,P<0.001),and the levels of CD3^(+),CD4^(+)and CD8^(+)were lower than those of the control group(41.69±5.39 vs 44.86±5.72,t=3.493,P=0.001;17.82±3.24 vs 23.69±3.86,t=10.087,P<0.001;18.05±2.81 vs 25.73±3.42,t=15.026,P<0.001).The serum KL-6 level in the moderate patients was higher than that in the mild patients(P<0.05);the serum KL-6 level in the study group was negatively correlated with the levels of CD4^(+)and CD8^(+)(r=-0.526,P<0.001,r=-0.713,P<0.001),and with the DSA 28 score,the degree of pulmonary ventilation disorder,and the degree of pulmonary diffusion dysfunction were positively correlated(r=0.429,P<0.001,r=0.802,P<0.001,r=0.851,P<0.001);the serum KL-6 levels in patients with poor efficacy before treatment 1 month,3 months and 6 months of treatment were higher than those in patients with good efficacy(P<0.05);the area under the curve(AUC)of serum KL-6 level before treatment for predicting poor efficacy in patients with RA and ILD was 0.838,and the predictive sensitivity and specificity were 75.02% and 88.14%,respectively.Conclusion:The level of serum KL-6 in RA patients with ILD is significantly increased,and its level is closely related to the abnormality of T lymphocyte subsets,and it can assist in clinical evaluation of patients'condition and predict curative effect,and has high application value.