Zhao J, Sun F, Li Y, Zhao X Z, Xu D, Li Y N, Li Y H, Sun X L
Beijing Da Xue Xue Bao Yi Xue Ban. 2020 Dec 18;52(6):1009-1013. doi: 10.19723/j.issn.1671-167X.2020.06.004.
To detect the serum level of a novel autoantibody, anti-tubulin-α-1C, in patients with systemic sclerosis (SSc) and to investigate its clinical significance.
Anti-tubulin-α-1C antibody levels were determined by enzyme-linked immunosorbent assay (ELISA) in 62 patients with SSc, 38 systemic lupus erythematosus (SLE), 24 primary Sjögren's syndrome (pSS) patients, and 30 healthy controls (HCs). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), immunoglobulin A(IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), C3, C4, rheumatoid factor (RF), antinuclear antibody(ANA), anti-centromere antibodies(ACA), anticardiolipin (aCL), anti-dsDNA antibody, anti-Sm antibody, anti-RNP antibody, anti-Scl-70 antibody, anti-Ro52 antibody, anti-SSA antibody, anti-SSB antibody, centromere protein A(CENP-A), centromere protein B (CENP-B) were measured by standard laboratory techniques. Raynaud's phenomenon and modified Rodnan skin score(MRSS) were recorded to evaluate the disease status of SSc. Independent sample test, Chi square test, Mann-Whitney test, Spearman rank correlation were used for statistical analyses.
The serum anti-tubulin-α-1C antibody concentration in SSc group was 81.24±34.38, the serum anti-tubulin-α-1C antibody concentration in SLE group was 87.84±38.52, the serum anti-tubulin-α-1C antibody concentration in pSS group was 59.79±25.24, and the serum anti-tubulin-α-1C antibody concentration in healthy group was 39.37±18.7. Multivariate analysis revealed that anti-tubulin-α-1C antibody levels were significantly increased in the SSc and SLE patients. The expression level of anti-tubulin-α-1C antibody in SSc was higher compared with the pSS group and the health control group ( < 0.01). Further analysis demonstrated that the elevated anti-tubulin-α-1C antibody were correlated with the SSc inflammation and disease activity markers ESR(=0.313, =0.019), The levels of anti-tubulin-α-1C antibody were also significantly correlated with MRSS(=0.636, < 0.01). The best cut-off value for the diagnose of SSc was 76.77 as mean+2SD value. The proportion of Raynaud's phenomenon was higher in the group of anti-tubulin-α-1C autoantibody-postive SSc patients than that in anti-tubulin-α-1C autoantibody negative group(71.4% . 37.5%, =0.039). The proportions of anti-Scl-70 antibody, anti-CENP antibody and anti-cardiolipin antibody were higher in the group of anti-tubulin-α-1C autoantibody-postive SSc patients than in the anti-tubulin-α-1C autoantibody negative group (37.9% . 15.2%, 34.5% . 12.1%, 13.8 . 0, respectively, all < 0.05).
Based on this explorative stu-dy, the level of anti-tubulin-α-1C antibody increased in the serum of the patients with SSc. There were correlations between anti-tubulin-α-1C autoantibody and clinical and laboratory indicators of the SSc patients. It may become a novel biomarker indicative of active SSc and could be applied in future clinical practice.
检测系统性硬化症(SSc)患者血清中一种新型自身抗体抗微管蛋白-α-1C的水平,并探讨其临床意义。
采用酶联免疫吸附测定(ELISA)法检测62例SSc患者、38例系统性红斑狼疮(SLE)患者、24例原发性干燥综合征(pSS)患者及30名健康对照者(HCs)血清中的抗微管蛋白-α-1C抗体水平。采用标准实验室技术检测红细胞沉降率(ESR)、C反应蛋白(CRP)、免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、免疫球蛋白G(IgG)、C3、C4、类风湿因子(RF)、抗核抗体(ANA)、抗着丝点抗体(ACA)、抗心磷脂(aCL)、抗双链DNA抗体、抗Sm抗体、抗RNP抗体、抗Scl-70抗体、抗Ro52抗体、抗SSA抗体、抗SSB抗体、着丝点蛋白A(CENP-A)、着丝点蛋白B(CENP-B)。记录雷诺现象和改良Rodnan皮肤评分(MRSS)以评估SSc的疾病状态。采用独立样本检验、卡方检验、Mann-Whitney检验、Spearman等级相关分析进行统计学分析。
SSc组血清抗微管蛋白-α-1C抗体浓度为81.24±34.38,SLE组血清抗微管蛋白-α-1C抗体浓度为87.84±38.52,pSS组血清抗微管蛋白-α-1C抗体浓度为59.79±25.24,健康组血清抗微管蛋白-α-1C抗体浓度为39.37±18.7。多因素分析显示,SSc和SLE患者的抗微管蛋白-α-1C抗体水平显著升高。SSc患者抗微管蛋白-α-1C抗体的表达水平高于pSS组和健康对照组(P<0.01)。进一步分析表明,抗微管蛋白-α-1C抗体升高与SSc炎症及疾病活动指标ESR相关(r=0.313,P=0.019),抗微管蛋白-α-1C抗体水平也与MRSS显著相关(r=0.636,P<0.01)。诊断SSc的最佳截断值为平均值+2SD值76.77。抗微管蛋白-α-1C自身抗体阳性的SSc患者组中雷诺现象的比例高于抗微管蛋白-α-1C自身抗体阴性组(71.4%对37.5%,P=0.039)。抗微管蛋白-α-1C自身抗体阳性的SSc患者组中抗Scl-70抗体、抗CENP抗体和抗心磷脂抗体的比例高于抗微管蛋白-α-1C自身抗体阴性组(分别为37.9%对15.2%,34.5%对12.1%,13.8%对0,均P<0.05)。
基于本探索性研究,SSc患者血清中抗微管蛋白-α-1C抗体水平升高。抗微管蛋白-α-1C自身抗体与SSc患者的临床及实验室指标之间存在相关性。它可能成为提示SSc活动的一种新型生物标志物,并可能应用于未来的临床实践。