Abstract
AbstractTo 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.
Highlights
To identify novel autoantibodies of Takayasu arteritis (TAK) using human protein (HuProt) array-based approach, a two-phase approach was adopted
241 non-TAK subjects were grouped into the healthy control group (n = 116; 37.6 ± 8.9 years old; 33.6% females) and the autoimmune disease control group, which was comprised of AAV (ANCA-associated vasculitis; n = 37; 55.3 ± 16.4 years old; 51.4% females), SS (Sjögren's syndrome; n = 28; 50.8 ± 15.2 years old; 67.9% females), rheumatoid arthritis (RA), and systemiclupusery thematosus (SLE)
To assess the quality of the protein arrays before performing the serum profiling assays, randomly selected HuProt and TAK-focused arrays were probed with anti-GST antibodies, and analyses of the obtained signal intensity values revealed a 93.2% detection rate with a correlation coefficient of 0.978 between the duplicate spots of the same protein for the HuProt arrays (Y = 0.99X + 0.53; R2 = 0.96), and a 100% detection rate with a correlation coefficient of 0.880 for the TAK-focused arrays (Y = 0.91X + 2.74; R2 = 0.77), suggesting reliable reproducibility
Summary
To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach, a two-phase approach was adopted. 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. The performances of three autoantibodies, namely anti-SPATA7, -QDPR, and -PRH2, were successfully confirmed with western blot analysis Using this twophase strategy, we identified and validated eight novel autoantibodies as TAK–specific biomarker candidates, three of which could be readily adopted in a clinical setting. Erythrocyte sedimentation rate (ESR) and C-reactive proteins (CRP) that are acutephase response reactants were used to monitor TAK activity in clinic, they cannot reliably quatify disease activity [4] Serum biomarkers, such as matrix metalloproteinase-9, TNF-α, and IL-6 [5, 6], were found to be increased in TAK, as well as other inflammatory diseases. Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking
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