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

Xiaoting Wen, Guang Song, Chaojun Hu, Jianbo Pan, Ziyan Wu, Liubing Li, Chenxi Liu, Xinping Tian, Fengchun Zhang, Jiang Qian, Heng Zhu, Yongzhe Li

Molecular & cellular proteomics : MCP 2021

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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. Copyright © 2021. Published by Elsevier Inc.

Citation

Xiaoting Wen, Guang Song, Chaojun Hu, Jianbo Pan, Ziyan Wu, Liubing Li, Chenxi Liu, Xinping Tian, Fengchun Zhang, Jiang Qian, Heng Zhu, Yongzhe Li. Identification of Novel Serological Autoantibodies in Takayasu Arteritis Patients Using HuProt Arrays. Molecular & cellular proteomics : MCP. 2021;20:100036