[Significance of anti-tubulin-α-1C autoantibody in systemic sclerosis]

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.
[Article in Chinese]

Abstract

Objective: 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.

Methods: 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 t test, Chi square test, Mann-Whitney U test, Spearman rank correlation were used for statistical analyses.

Results: 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 (P < 0.01). Further analysis demonstrated that the elevated anti-tubulin-α-1C antibody were correlated with the SSc inflammation and disease activity markers ESR(r=0.313, P=0.019), The levels of anti-tubulin-α-1C antibody were also significantly correlated with MRSS(r=0.636, P < 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% vs. 37.5%, P=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% vs. 15.2%, 34.5% vs. 12.1%, 13.8 vs. 0, respectively, all P < 0.05).

Conclusion: 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.

目的: 检测抗α-1C微管蛋白(tubulin-α-1C)抗体在系统性硬化症(systemic sclerosis, SSc)患者血清中的表达,并探讨其潜在的临床意义。

方法: 入组SSc患者62例、系统性红斑狼疮(systemic lupus erythematosus, SLE)患者38例、原发性干燥综合征(primary Sjögren's syndrome, pSS)患者24例和健康对照组(health control, HC)30例,收集血清,采用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)分别检测各组血清中抗tubulin-α-1C抗体水平。同时,用标准实验室技术测定红细胞沉降率(erythrocyte sedimentation rate, ESR)、C反应蛋白(C-reactive protein, CRP)、免疫球蛋白A(Immunoglobulin A, IgA)、免疫球蛋白M(Immunoglobulin M, IgM)、免疫球蛋白G(Immunoglobulin G, IgG)、补体C3、补体C4、类风湿因子(rheumatoid factor, RF)、抗核抗体(antinuclear antibody, ANA)、抗着丝点抗体(anti-centromere antibodies, ACA)、抗心磷脂抗体(anticardiolipin, aCL)、抗双链DNA抗体(抗dsDNA抗体)、抗Sm抗体、抗RNP抗体、抗Scl-70抗体、抗Ro-52抗体、抗SSA抗体、抗SSB抗体、着丝点蛋白A(centromere protein A, CENP-A)、着丝点蛋白B(centromere protein B, CENP-B)等指标。记录雷诺现象和改良的Rodnan评分(modified Rodnan skin score, MRSS)等临床表现来评估SSc的疾病状态,分析抗tubulin-α-1C抗体与其他实验室指标和临床表现的关系。组间计量资料比较采用两独立样本t检验或Mann-Whitney U检验; 组间计数资料比较采用卡方检验; 采用绘制实验组工作曲线确定抗tubulin-α-1C抗体对诊断SSc最佳截断值并分析其诊断效能,相关性分析采用Spearman相关分析。

结果: SSc患者、SLE患者、pSS患者和正常对照组血清中抗tubulin-α-1C抗体水平分别为81.24±34.38、87.84±38.52、59.79±25.24、39.37±18.7,SSc患者血清抗tubulin-α-1C抗体水平显著高于pSS患者和正常对照组,P均小于0.001。SSc患者血清抗tubulin-α-1C抗体水平与SLE组差异没有统计学意义。Spearman相关性分析示抗tubulin-α-1C抗体与SSc炎症和疾病活性标志物ESR正相关(r=0.313,P=0.019),与MRSS正相关(r=0.636, P < 0.01)。根据正常对照组表达抗tubulin-α-1C抗体x±2s定义阳性阈值为76.77,将SSc患者分为抗tubulin-α-1C抗体阳性组和阴性组,抗tubulin-α-1C抗体阳性组出现雷诺现象的比例明显高于阴性组(71.4% vs. 37.5%, P=0.039);抗tubulin-α-1C抗体阳性组中抗Scl-70抗体、ACA抗体和aCL抗体的阳性率也显著高于阴性组(分别为37.9% vs. 15.2%,P=0.041; 34.5% vs. 12.1%, P=0.035; 13.8 vs. 0, P=0.027)。

结论: 抗tubulin-α-1C抗体在SSc患者血清中异常升高,可能成为一种新的生物标志物用于SSc的临床诊断和风险预测。

Keywords: Anti-tubulin-α-1C antibody; Autoantibodies; Systemic sclerosis.

MeSH terms

  • Antibodies, Antinuclear
  • Autoantibodies
  • Humans
  • Lupus Erythematosus, Systemic*
  • Scleroderma, Systemic*
  • Sjogren's Syndrome*

Substances

  • Antibodies, Antinuclear
  • Autoantibodies

Grants and funding

国家自然科学基金(81801617)