泛素羧基末端水解酶-1抗原表位自身抗体在干燥综合征筛查诊断中的临床意义

Clinical significance of autoantibodies against ubiquitin carboxyl hydrolase L1 epitopes in the screening and diagnosis of Sjögren syndrome

目的研究泛素羧基末端水解酶-1(UCH-L1)抗原表位自身抗体在干燥综合征(SS)筛查诊断中的临床意义。方法用ELISA检测2017年1月至2020年1月于郑州大学第五附属医院和北京大学人民医院就诊的98例SS患者[男17例,女81例,年龄(49.1±12.3)岁]和37名体检健康志愿者[对照组,男6名,女31名,年龄(46.3±5.8)岁]血清UCH-L1抗原表位自身抗体的水平。分析与合成UCH-L1三种潜在的抗原表位肽段,最终抗UCH-L1^(203-214)抗体和抗UCH-L1^(58-69)抗体进入研究,比较两组抗UCH-L1抗体水平,并使用Pearson相关分析UCH-L1与患者临床资料的相关性。结果SS组血清中抗UCH-L1^(203-214)抗体水平显著高于健康对照组(108.2±54.3比78.9±25.8,P<0.001)。SS组血清中抗UCH-L1^(58-69)抗体水平显著高于健康对照组(86.8±33.3比60.4±21.5,P<0.001)。SS患者血清中抗UCH-L1^(203-214)抗体及抗UCH-L1^(58-69)抗体阳性率分别为27.6%(27/98)和25.5%(25/98),健康对照组分别为2.7%(1/37)和5.4%(2/37)。在血清抗UCH-L1^(58-69)抗体阳性的SS患者中,血清IgG、γ球蛋白及类风湿因子(RF)水平及抗SS相关抗原B(SSB)抗体阳性率均高于抗UCH-L1^(58-69)抗体阴性患者,差异均有统计学意义(均P<0.05)。SS组,在抗核抗体(ANA)、抗RNA结合蛋白(RNP)抗体、抗SSA抗体、抗SSB抗体阴性患者中抗UCH-L1^(203-214)抗体阳性率分别为32.1%(9/28)、27.2%(25/92)、36.4%(12/33)、28.6%(18/63);抗UCH-L1^(58-69)抗体阳性率分别为21.4%(6/28)、30.4%(28/92)、30.3%(10/33)、20.6%(13/63)。血清抗UCH-L1^(203-214)抗体水平与SS患者血清IgA水平呈正相关(r=0.21,P=0.024);抗UCH-L1^(58-69)抗体水平与SS患者血清γ球蛋白、IgG、RF水平均呈正相关(r=0.35、0.33、0.32,均P<0.01)。结论UCH-L1抗原表位自身抗体与SS患者某些临床指标具有相关性,对SS的筛查及诊断具有一定意义。

Objective To study the clinical significance of autoantibodies against different ubiquitin carboxyl hydrolase L1(UCH-L1)epitopes in Sjogren syndrome(SS).Methods The serum levels of different UCH-L1 epitope autoantibodies in 98 SS patients[SS group,17 males and 81 females,aged(49.1±12.3)years]in the Fifth Affiliated Hospital of Zhengzhou University and Peking University People's Hospital from January 2017 to January 2020 and 37 healthy controls[control group,6 males and 31 females,aged(46.3±5.8)years]were determined by enzyme-linked immunosorbent assay(ELISA).Three potential epitopes of UCH-L1 protein were analyzed and synthesized and anti-UCH-L1^(203-214) and anti-UCH-L1^(58-69) antibodies were studied between the two groups.The levels of the two anti-UCH-L1 antibodies in the two groups were compared.The correlation between the levels of UCH-L1 antibodies and clinical data of SS patients were analyzed by Pearson correlation analysis.Results The serum levels of anti-UCH-L1^(203-214) and anti-UCH-L1^(58-69) antibody in SS patients were significantly higher than those in healthy controls(HCs)(anti-UCH-L1^(203-214):108.2±54.3 vs 78.9±25.8,P<0.001,anti-UCH-L1^(58-69):86.8±33.3 vs 60.4±21.5,P<0.001).The positive rates of anti-UCH-L1^(203-214) and anti-UCH-L1^(58-69) antibodies in serums of SS patients were 27.6%(27/98)and 25.5%(25/98),and those in HCs were 2.7%(1/37)and 5.4%(2/37),respectively.In SS patients with positive serum anti-UCH-L1^(58-69) antibody,the levels of IgG,γglobulin and rheumatoid factor(RF)and anti-SS-related antigen B(anti-SSB)antibody positive rate were all significantly higher than those in patients with negative antibody(all P<0.05).In SS patients with negative antinuclear antibody(ANA),anti-RNA binding protein(anti-RNP)antibody,anti-SS-related antigen A(anti-SSA)antibody and anti-SSB antibody,the positive rates of anti-UCH-L1^(203-214) antibody was 32.1%(9/28),27.2%(25/92),36.4%(12/33),28.6%(18/63),respectively;and the positive rates of anti-UCH-L1^(58-69) antibody was 21.4%(6/28),30.4%(28/92),30.3%(10/33),20.6%(13/63),respectively.The level of serum anti-UCH-L1^(203-214) antibody in SS patients was positively correlated with the IgA level(r=0.21,P=0.024).The level of anti-UCH-L1^(58-69) antibody in SS patients was positively correlated with the levels ofγ-globulin,IgG and RF(r=0.35,0.33,0.32,all P<0.01).Conclusion Autoantibodies against UCH-L1 epitopes are correlated with some clinical parameters of SS patients,which is of promising significance in the screening and diagnosis of SS.