炎症因子及活动度在类风湿关节炎患者干眼中的表达变化及其意义

Expression and the value of inflammatory factors and diseaseactivity in dry eyes of patients with rheumatoid arthritis

目的研究炎症因子及活动度在RA患者干眼中的表达变化及其意义。方法收集2017年3月至2019年11月在我院风湿免疫科确诊并治疗的RA合并干眼患者78例,眼科门诊就诊的单纯性干眼患者80例和健康志愿者80名。所有研究对象均接受干眼相关指标检测:眼表疾病指数(OSDI)问卷评分、泪膜破裂时间(BUT)、泪液分泌试验(SIT)及角膜荧光素染色(FL)评分。采集类风湿活动度相关的指标:ESR、CRP、RF。采用双抗体夹心ELISA检测泪液中炎症因子:IL-1β、TNF-α、趋化因子3(CCL3)、CCL4、CCL5及血管内皮生长因子(VEGF)的浓度。3组间各项相关指标使用单因素方差分析,多重比较采用LSD-t法。采用Pearson方法分析RA活动度相关指标与干眼相关各项指标的相关性。结果3组间OSDI[(44±9)分和(44±9)分和(24±7)分]、SIT[(3.3±2.2)mm/5 min和(3.6±2.1)mm/5 min和(11.7±1.6)mm/5 min]、BUT[(4.3±1.8)s和(5.9±1.9)s和(10.4±2.0)s]、FL[(7.3±3.1)分和(5.7±2.8)分和(1.6±1.6)分]比较,差异均有统计学意义(F=154.22,P<0.01;F=470.49,P<0.01;F=217.72,P<0.01;F=101.99,P<0.01)。3组间患者泪液中IL-1β[(1.92±0.14)和(1.28±0.18)和(0.64±0.15)ng/L]、IL-6[(38.2±0.7)ng/L和(36.3±0.8)ng/L和(30.4±0.9)ng/L]、TNF-α[(0.78±0.03)ng/L和(0.67±0.03)ng/L和(0.56±0.02)ng/L]、CCL3[(91±25)ng/L和(83±21)ng/L和(24±18)ng/L]、CCL4[(187±76)ng/L和(137±64)ng/L和(37±5)ng/L]、CCL5[(259±70)ng/L和(182±42)ng/L和(135±34)ng/L]及VEGF[(172±25)ng/L和(152±22)ng/L和(41±21)ng/L]的浓度相比,3组间差异均有统计学意义(F=1300.15,P<0.01;F=2036.37,P<0.01;F=1305.89,P<0.01;F=764.01,P<0.01;F=225.47,P<0.01;F=138.48,P<0.01;F=121.04,P<0.01)。3组间风湿活动度指标(ESR、CRP、RF)比较,RF阳性率[(100%)和(5%)和(4%)]在RA干眼组高于其余2组,差异有统计学意义(χ^2=127.38,P<0.01)。3组间ESR[(51±23)mm/1 h和(9±4)mm/1 h和(8±5)mm/1 h]、CRP[(44±23)g/L和(5±4)g/L和(6±4)g/L]比较,总体差异均有统计学意义(F=253.18,P<0.01;F=222.36,P<0.01)。RA干眼组中BUT与活动度指标(ESR、CRP、RF)均呈负相关(r=-0.398,P=0.005;r=-0.353,P=0.010;r=-0.302,P=0.038),FL与活动度指标(ESR、CRP、RF)均呈正相关(r=0.345,P=0.014、r=0.385,P=0.007;r=0.412、P=0.003),SIT、OSDI与活动度指标(ESR、CRP、RF)无相关性(r=-0.265,P=0.060;r=-0.156,P=0.318、r=0.275,P=0.070);(r=-0.087,P=0.582;r=-0.065,P=0.664;r=-0.045,P=0.768)。结论炎症因子和风湿活动性指标在RA干眼患者中高表达,RA的疾病活动度与干眼之间呈相关性,具有临床指导意义。

Objective To study the expression and value of inflammatory factors and disease activity in dry eyes of rheumatoid arthritis patients.Methods From March 2017 to November 2019,78 patients with rheumatoid arthritis complicated with dry eye diagnosed by the rheumatology department of our hospital,80 patients with simple dry eye treated in the ophthalmology clinic and 80 normal volunteers were collected.All subjects were examined for OSDI questionnaire scores,tear film rupture time(BUT),tear secretion test(SIT),and corneal fluorescein staining(FL)scores.Erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),rheumatoid factor(RF)and other disease activity-related indicators were collected.The concentrations of interleukin-1b(il-1b),tumor necrosis factor-a(tnf-a),chemokine 3(CCL3),CCL4,CCL5,and vascular endothelial growth factor(VEGF)in the collected tears were detected by double-antibody sandwich enzyme-linked immunosorbent assay(ELISA).One-way Anova was used to analyze the correlative indexes among the three groups,LSD-t method was used for multiple comparison.Pearson's method was used to analyze the correlation between Ra activity and dry eye.Results The results of OSDI[(44±9)points vs(44±9)points vs(24±7)points],SIT[(3.3±2.2)mm/5 min vs(3.6±2.1)mm/5 min vs(11.7±1.6)mm/5 min],BUT[(4.3±1.8)s vs(5.9±1.9)s vs(10.4±2.0)s],FL[(7.3±3.1)points vs(5.7±2.8)points vs(1.6±1.6)points]were com-pared among the three groups.There were significant differences among the three groups(F=154.22,P<0.01;F=470.49,P<0.01;F=217.72,P<0.01;F=101.99,P<0.01).The concentrations of IL-1β[(1.92±0.14)ng/L vs(1.28±0.18)ng/L vs(0.64±0.15)ng/L],IL-6[(38.24±0.69)ng/L vs(36.31±0.82)ng/L vs(30.43±0.87)ng/L]、TNF-α[(0.78±0.03)ng/L vs(0.67±0.03)ng/L vs(0.56±0.02)ng/L],CCL3[(91±25)ng/L vs(83±21)ng/L vs(24±18)ng/L],CCL4[(187±76)ng/L vs(137±64)ng/L vs(37±5)ng/L],CCL5[(259±70)ng/L vs(182±42)ng/L vs(135±34)ng/L]and VEGF[(172±25)ng/L vs(152±22)ng/L vs(41±21)ng/L]in the tears of the three groups were significantly different(F=1300.15,P<0.01;F=2036.37,P<0.01;F=1305.89,P<0.01;F=764.01,P<0.01;F=225.47,P<0.01;F=138.48,P<0.01;F=121.04,P<0.01).The indexes of disease activity(ESR,CRP,RF)were compared among the three groups.The positive rate of RF[(100%)vs(5%)vs(4%)]was significantly higher in Ra dry eye group than in the other two groups(χ^2=127.38,P<0.01)There were significant differences in ESR[(51±23)mm/1 h vs(9±4)mm/1 h vs(8±5)mm/1 h]and CRP[(44±23)g/L vs(5±4)g/L vs(6±4)g/L]among the three groups(F=253.18,P<0.01;F=222.36,P<0.01).BUT was negatively correlated with the activity index(ESR,CRP,RF)in rheumatoid arthritis dry eye group(r=-0.398,P=0.005;r=-0.353,P=0.010;r=-0.302,P=0.038),FL was positively correlated with activity index(ESR,CRP,RF)(r=0.345,P=0.014;r=0.385,P=0.007;r=0.412,P=0.003).There was no correlation between SIT,OSDI and activity index(ESR,CRP,RF)(r=-0.265,P=0.060;r=-0.156,P=0.318;r=-0.275,P=0.070);(r=-0.087,P=0.582、r=-0.065,P=0.664;r=-0.045,P=0.768).Conclusion Inflammatory factors and disease activity indexes are highly expressed in rheumatoid arthritis patients with dry eye of disease,and there is a correlation between disease activity of rheumatoid arthritis and dry eye,which has some clinical meaing.