University of California, Los Angeles, USA.
Arthritis Care Res (Hoboken). 2010 Nov;62(11):1633-8. doi: 10.1002/acr.20289. Epub 2010 Jul 8.
Sjögren’s syndrome (SS) is a systemic autoimmune disease with a variety of presenting symptoms that may delay its diagnosis. We previously discovered a number of candidate salivary biomarkers for primary SS using both mass spectrometry and expression microarray analysis. In the current study, we aimed to verify these candidate biomarkers in independent patient populations and to evaluate their predictive values for primary SS detection.
In total, 34 patients with primary SS, 34 patients with systemic lupus erythematosus (SLE), and 34 healthy individuals were enrolled for the validation studies. Salivary protein biomarkers were measured using either Western blotting or enzyme-linked immunosorbent assay, and the messenger RNA (mRNA) biomarkers were measured using quantitative polymerase chain reaction. Statistical analysis was performed using R software, version 2.9.
Three protein biomarkers (cathepsin D [CPD], α-enolase, and ß₂-microglobulin [ß₂m]) and 3 mRNA biomarkers (myeloid cell nuclear differentiation antigen [MNDA], guanylate binding protein 2 [GBP-2], and low-affinity IIIb receptor for the Fc fragment of IgG) were significantly elevated in patients with primary SS compared with both SLE patients and healthy controls. The combination of 3 protein biomarkers, CPD, α-enolase, and ß₂m, yielded a receiver operating characteristic (ROC) value of 0.99 in distinguishing primary SS from healthy controls. The combination of protein biomarkers ß₂m and 2 mRNA biomarkers, MNDA and GBP-2, reached an ROC of 0.95 in discriminating primary SS from SLE.
We have successfully verified a panel of protein and mRNA biomarkers that can discriminate primary SS from both SLE and healthy controls. If further validated in patients with primary SS and those with sicca symptoms but no autoimmune disease, these biomarkers may lead to a simple yet highly discriminatory clinical tool for diagnosis of primary SS.
干燥综合征（SS）是一种系统性自身免疫性疾病，具有多种表现症状，可能会延迟其诊断。我们之前使用质谱和表达微阵列分析发现了一些原发性 SS 的候选唾液生物标志物。在本研究中，我们旨在在独立的患者群体中验证这些候选生物标志物，并评估它们对原发性 SS 检测的预测价值。
共纳入 34 例原发性 SS 患者、34 例系统性红斑狼疮（SLE）患者和 34 例健康对照者进行验证研究。使用 Western 印迹或酶联免疫吸附试验测量唾液蛋白生物标志物，使用定量聚合酶链反应测量信使 RNA（mRNA）生物标志物。使用 R 软件（版本 2.9）进行统计分析。
与 SLE 患者和健康对照者相比，原发性 SS 患者的 3 种蛋白标志物（组织蛋白酶 D [CPD]、α-烯醇化酶和β₂-微球蛋白[β₂m]）和 3 种 mRNA 标志物（髓样细胞核分化抗原[MNDA]、鸟苷酸结合蛋白 2 [GBP-2]和低亲和力 IIIb 受体 IgG Fc 片段）显著升高。3 种蛋白标志物（CPD、α-烯醇化酶和β₂m）的组合在区分原发性 SS 与健康对照者时获得了 0.99 的受试者工作特征（ROC）值。蛋白标志物β₂m 与 2 种 mRNA 标志物 MNDA 和 GBP-2 的组合在区分原发性 SS 与 SLE 时达到了 0.95 的 ROC。
我们成功验证了一组蛋白和 mRNA 生物标志物，可区分原发性 SS 与 SLE 和健康对照者。如果在原发性 SS 患者和有干燥症状但无自身免疫性疾病的患者中进一步验证，这些生物标志物可能会导致一种简单而高度有鉴别力的临床工具，用于原发性 SS 的诊断。
