An autoantibody profile identified by human genome‐wide protein arrays in rheumatoid arthritis
Xu Liu,
Xiaoying Zhang,
Yu‐Jian Kang,
Fei Huang,
Shuang Liu,
Yixue Guo,
Yingni Li,
Changcheng Yin,
Mingling Liu,
Qimao Han,
Qingwen Wang,
Hua Ye,
Haihong Yao,
Chun Li,
Jiahe Li,
Wangzha Pingcuo,
Yan Zhang,
Yin Su,
Ge Gao,
Zhanguo Li,
Xiaolin Sun
Affiliations
Xu Liu
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Xiaoying Zhang
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Yu‐Jian Kang
Chongqing Key Laboratory of Intelligent Oncology for Breast Cancer Cancer Hospital School of Medicine Chongqing University Chongqing China
Fei Huang
General Medical Department Huazhong University of Science and Technology Union Shenzhen Hospital Shenzhen China
Shuang Liu
Department of Rheumatology and Immunology First Affiliated Hospital of Kunming Medical University. Kunming China
Yixue Guo
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Yingni Li
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Changcheng Yin
Beijing Protein Innovation B‐8, Airport Industrial Zone Beijing China
Mingling Liu
Department of Rheumatology the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou China
Qimao Han
Department of Rheumatology The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine. No.24 Heping Road Xiangfang District Harbin China
Qingwen Wang
Department of Rheumatism and Immunology Peking University Shenzhen Hospital Shenzhen China
Hua Ye
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Haihong Yao
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Chun Li
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Jiahe Li
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Wangzha Pingcuo
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Yan Zhang
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Yin Su
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Ge Gao
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences Biomedical Pioneering Innovative Center (BIOPIC) & Beijing Advanced Innovation Center for Genomics (ICG) Center for Bioinformatics (CBI) Peking University Beijing China
Zhanguo Li
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Xiaolin Sun
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing China
Abstract Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)‐negative and early‐stage RA are still to be improved. We aimed to screen autoantibodies in ACPA‐negative patients and evaluated their diagnostic performance. The human genome‐wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti‐ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA‐negative RA, including anti‐ANAPC15, anti‐LSP1, anti‐APBB1, anti‐parathymosin, and anti‐UBL7. Anti‐parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA‐negative early stage (<2 years) RA. To further improve the diagnostic efficacy, a prediction model was constructed with 44 autoantibodies. With increased threshold for RA calling, the specificity of the model is 90.8%, while the sensitivity is 66.1% (87.8% in ACPA‐positive RA and 23.8% in ACPA‐negative RA) in independent testing patients. Therefore, HuProt arrays identified RA‐associated autoantibodies that might become possible diagnostic markers, especially in early stage ACPA‐negative RA.