类风湿关节炎合并肺间质病变的临床特点及与白介素33及其受体人基质裂解素2的相关性研究

The Clinical Characteristic of Rheumatoid Arthritis-associated Interstitial Lung and the Correlation with IL-33 and ST2

目的探讨类风湿关节炎合并肺间质病变(RA-ILD)患者的临床、实验室特征及与细胞因子白介素33(IL-33)及其受体人基质裂解素2(ST2)的相关性,为RA-ILD的早期诊断提供依据。方法收集我院风湿免疫科初诊为类风湿关节炎(RA)患者114例,进一步分为RA-ILD组(21例)和RA组(93例),观察各组的临床症状及实验室指标,另选取健康体检者30例为对照组。酶联免疫吸附实验(ELISA)法测定以上各组参加者的血清IL-33及其受体ST2水平。结果 (1)RA-ILD在RA患者中的发生率为18.4%(21/114)。(2)与RA组相比,RA-ILD组患者年龄较大,病程较长,晨僵时间长,压痛关节数、肿胀关节数均较多,关节功能分级和手X线分期较严重,差异有统计学意义(P<0.01);且C-反应蛋白(CRP)、红细胞沉降率(ERS)、类风湿因子(RF)、抗环瓜氨酸多肽抗体(ACPA)、疾病活动度评分(DAS28)也均较高,差异有统计学意义(P<0.05);两病例组肺活量(VC)、用力肺活量(FVC)、最大呼气中段流量(MMF)和一氧化碳弥散量(DLCO)四项指标间差异有统计学意义(P<0.01)。(3)与对照组相比,两病例组血清IL-33及ST2水平均增高,差异有统计学意义(P<0.01);且RA-ILD组高于RA组,差异有统计学意义(P<0.01)。(4)IL-33水平与RF、ACPA滴度呈正相关(r值分别为0.817、0.550,P<0.01);与DLCO水平呈负相关(r=-0.801,P<0.01)。结论 RA-ILD易发生于年龄偏大、病程较长的RA患者中,且与疾病活动度及ACPA有关;血清IL-33及ST2参与了RA的发病过程,且可能与RA-ILD的发病有关;IL-33水平增高可能为RA预后不良的因素。

Objective To explore the clinical and laboratory features of patients with rheumatoid arthritis complicate by interstitial lung disease （RA -ILD） and their correlation with interleukin -33 （IL -33） and its receptor or human stromely- sin - 2 （ ST2）, in order to provide the basis for an early diagnosis of RA - ILD. Methods Among 114 patients newly diagnosed as having RA in the rheumatism immune department there were 21 who at the same time had ILD （RA -ILD group）, and 93 who had no ILl） （RA group）. And 30 healthy persons from our examination center were recruited as the controls. The clinical symptoms and laboratory parameters were observed in each group, the levels of serum IL - 33 and its receptor ST2 concentration were determined by ELISA. Results （1） The incidence of ILD in RA patients was 18.4% （21/114）. （2） Compared with RA group, in the RA -ILD group the patients was older in age, their course of disease was longer, their morning stiffness of joints was longer, the numbers of joint with tender and swollen were larger, and their joint dysfunction and lesion of hand X -ray were severer （P 〈0. 01 ）. At the same time their levels of C -reactive protein, erythromycin sedimentation rate, rheumatoid factor （ RF）, anti - citrullinated peptide antibody （ ACPA）, disease activity score （ DAS28 ） were all higher （ P 〈 O. 05 ）. And the differences between the two groups in vital capacity （VC）, forced vital capacity （FVC）, maximum middle expiratory flow （MMF） and carbon monoxide - diffusing capacity （DLCO） were statistically significant （ P 〈 0. 01 ）. （ 3 ） Compared with the control group, in the two groups the levels of IL - 33 and ST2 were significantly increased （ P 〈 0. 01 ）, and the levels were significantly higher in the RA -ILI） group than in the RA group （P 〈0.01）. （4） The level of IL-33 was correlated with levels of RF and ACPA positively （r =0. 817, 0. 550, P 〈0. 01）, and with DLCO negatively （r = -0. 801, P 〈0.01 ）. Conclusion RA - ILD is common in older patients and those whose course is longer; and it is associated with disease activity and ACPA. The plasma IL - 33 and ST2 are involved in the pathogenesis of RA and may participate in the pathogenesis of RA - ILD. And the increased IL -33 may be a risk factor for prognosis of RA.