Tracking the Antibody Immunome in Type 1 Diabetes Using Protein Arrays

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• 作者：Xiaofang Bian ; Clive Wasserfall ; Garrick Wallstrom ; Jie Wang ; Haoyu Wang ; Kristi Barker ; Desmond Schatz ; Mark Atkinson ; Ji Qiu ; Joshua LaBaer
• 刊名：Journal of Proteome Research
• 出版年：2017
• 出版时间：January 6, 2017
• 年：2017
• 卷：16
• 期：1
• 页码：195-203
• 全文大小：482K
• ISSN：1535-3907

文摘

We performed an unbiased proteome-scale profiling of humoral autoimmunity in recent-onset type 1 diabetes (T1D) patients and nondiabetic controls against ∼10 000 human proteins using a Nucleic Acid Programmable Protein Array (NAPPA) platform, complemented by a knowledge-based selection of proteins from genes enriched in human pancreas. Although the global response was similar between cases and controls, we identified and then validated six specific novel T1D-associated autoantibodies (AAbs) with sensitivities that ranged from 16 to 27% at 95% specificity. These included AAbs against PTPRN2, MLH1, MTIF3, PPIL2, NUP50 (from NAPPA screening), and QRFPR (by targeted ELISA). Immunohistochemistry demonstrated that NUP50 protein behaved differently in islet cells, where it stained both nucleus and cytoplasm, compared with only nuclear staining in exocrine pancreas. Conversely, PPIL2 staining was absent in islet cells, despite its presence in exocrine cells. The combination of anti-PTPRN2, -MLH1, -PPIL2, and -QRFPR had an AUC of 0.74 and 37.5% sensitivity at 95% specificity. These data indicate that these markers behave independently and support the use of unbiased screening to find biomarkers because the majority was not predicted based on predicted abundance. Our study enriches the knowledge of the “autoantibody-ome” in unprecedented breadth and width.