Identification of Novel Serological Autoantibodies in Takayasu Arteritis Patients Using HuProt Arrays

• Published in: Molecular & cellular proteomics Vol. 20; p. 100036
• Main Authors: Wen, Xiaoting, Song, Guang, Hu, Chaojun, Pan, Jianbo, Wu, Ziyan, Li, Liubing, Liu, Chenxi, Tian, Xinping, Zhang, Fengchun, Qian, Jiang, Zhu, Heng, Li, Yongzhe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2021
• Subjects: autoantibody; biomarker; protein microarray; Takayasu arteritis; CRP; SS; autoantibody; ESR; protein microarray; AAV; Takayasu arteritis; biomarker; SLE; TAK; RA; Micro Arrays; Biomarker: Diagnostic; Plasma or serum analysis; Serological markers; Blood; takayasu arteritis
• ISSN: 1535-9476; 1535-9484; 1535-9484
• DOI: 10.1074/mcp.RA120.002119

To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach, a two-phase approach was adopted. In Phase I, serum samples collected from 40 TAK patients, 15 autoimmune disease patients, and 20 healthy subjects were screened to identify TAK-specific autoantibodies using human protein (HuProt) arrays. In phase II, the identified candidate autoantibodies were validated with TAK-focused arrays using an additional cohort comprised of 109 TAK patients, 110 autoimmune disease patients, and 96 healthy subjects. Subsequently, the TAK-specific autoantibodies validated in phase II were further confirmed using western blot analysis. We identified and validated eight autoantibodies as potential TAK-specific diagnostic biomarkers, including anti-SPATA7, -QDPR, -SLC25A2, -PRH2, -DIXDC1, -IL17RB, -ZFAND4, and -NOLC1 antibodies, with AUC of 0.803, 0.801, 0.780, 0.696, 0.695, 0.678, 0.635, and 0.613, respectively. SPATA7 could distinguish TAK from healthy and disease controls with 73.4% sensitivity at 85.4% specificity, while QDPR showed 71.6% sensitivity at 86.4% specificity. SLC25A22 showed the highest sensitivity of 80.7%, but at lower specificity of 67.0%. In addition, PRH2, IL17RB, and NOLC1 showed good specificities of 88.3%, 85.9%, and 86.9%, respectively, but at lower sensitivities (<50%). Finally, DIXDC1 and ZFAND4 showed moderate performance as compared with the other autoantibodies. Using a decision tree model, we could reach a specificity of 94.2% with AUC of 0.843, a significantly improved performance as compared with that by each individual biomarker. The performances of three autoantibodies, namely anti-SPATA7, -QDPR, and -PRH2, were successfully confirmed with western blot analysis. Using this two-phase strategy, we identified and validated eight novel autoantibodies as TAK–specific biomarker candidates, three of which could be readily adopted in a clinical setting. [Display omitted] •HuProt array and TAK-focused arrays were adopted to identify TAK-specific biomarkers.•Eight autoantibodies were identified as potential TAK-specific biomarkers.•The decision tree model could significantly improve biomarker performance.•Anti-SPATA7, -QDPR, and -PRH2 might be potentially adopted in a clinical setting. A two-phase approach was adopted to identify novel autoantibody biomarkers of Takayasu arteritis (TAK) patients. HuProt array together with a TAK-focused array identified eight novel autoantibodies as TAK-specific biomarker candidates. Of them, the anti-SPATA7, -QDPR, and -PRH2 have the potential to be readily adopted in a clinical setting.