Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies (autoAbs) in patients’ blood. However, the full spectrum of autoAbs in SLE has not been comprehensively elucidated. In this study, a commercial platform bearing 9400 antigens (Prot...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Genomics, Proteomics & Bioinformatics |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S167202291930124X |
| _version_ | 1797368590417002496 |
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| author | Hui Luo Ling Wang Ding Bao Li Wang Hongjun Zhao Yun Lian Mei Yan Chandra Mohan Quan-Zhen Li |
| author_facet | Hui Luo Ling Wang Ding Bao Li Wang Hongjun Zhao Yun Lian Mei Yan Chandra Mohan Quan-Zhen Li |
| author_sort | Hui Luo |
| collection | DOAJ |
| description | Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies (autoAbs) in patients’ blood. However, the full spectrum of autoAbs in SLE has not been comprehensively elucidated. In this study, a commercial platform bearing 9400 antigens (ProtoArray) was used to identify autoAbs that were significantly elevated in the sera of SLE patients. By comparing the autoAb profiles of SLE patients with those of healthy controls, we identified 437 IgG and 1213 IgM autoAbs that the expression levels were significantly increased in SLE (P < 0.05). Use of the ProtoArray platform uncovered over 300 novel autoAbs targeting a broad range of nuclear, cytoplasmic, and membrane antigens. Molecular interaction network analysis revealed that the antigens targeted by the autoAbs were most significantly enriched in cell death, cell cycle, and DNA repair pathways. A group of autoAbs associated with cell apoptosis and DNA repair function, including those targeting APEX1, AURKA, POLB, AGO1, HMGB1, IFIT5, MAPKAPK3, PADI4, RGS3, SRP19, UBE2S, and VRK1, were further validated by ELISA and Western blot in a larger cohort. In addition, the levels of autoAbs against APEX1, HMGB1, VRK1, AURKA, PADI4, and SRP19 were positively correlated with the level of anti-dsDNA in SLE patients. Comprehensive autoAb screening has identified novel autoAbs, which may shed light on potential pathogenic pathways leading to lupus. Keywords: Systemic lupus erythematosus, Autoantibodies, ProtoArray, Apoptosis, DNA repair |
| first_indexed | 2024-03-08T17:34:50Z |
| format | Article |
| id | doaj.art-65b2ce78f3af431785327c68fe24a785 |
| institution | Directory Open Access Journal |
| issn | 1672-0229 |
| language | English |
| last_indexed | 2024-03-08T17:34:50Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Genomics, Proteomics & Bioinformatics |
| spelling | doaj.art-65b2ce78f3af431785327c68fe24a7852024-01-02T13:07:28ZengElsevierGenomics, Proteomics & Bioinformatics1672-02292019-06-01173248259Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus ErythematosusHui Luo0Ling Wang1Ding Bao2Li Wang3Hongjun Zhao4Yun Lian5Mei Yan6Chandra Mohan7Quan-Zhen Li8Department of Rheumatology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Nephrology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072, ChinaSchool of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, ChinaDepartment of Rheumatology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Rheumatology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Biomedical Engineering, University of Houston, Houston, TX 77004, USADepartment of Rheumatology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Corresponding author.Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies (autoAbs) in patients’ blood. However, the full spectrum of autoAbs in SLE has not been comprehensively elucidated. In this study, a commercial platform bearing 9400 antigens (ProtoArray) was used to identify autoAbs that were significantly elevated in the sera of SLE patients. By comparing the autoAb profiles of SLE patients with those of healthy controls, we identified 437 IgG and 1213 IgM autoAbs that the expression levels were significantly increased in SLE (P < 0.05). Use of the ProtoArray platform uncovered over 300 novel autoAbs targeting a broad range of nuclear, cytoplasmic, and membrane antigens. Molecular interaction network analysis revealed that the antigens targeted by the autoAbs were most significantly enriched in cell death, cell cycle, and DNA repair pathways. A group of autoAbs associated with cell apoptosis and DNA repair function, including those targeting APEX1, AURKA, POLB, AGO1, HMGB1, IFIT5, MAPKAPK3, PADI4, RGS3, SRP19, UBE2S, and VRK1, were further validated by ELISA and Western blot in a larger cohort. In addition, the levels of autoAbs against APEX1, HMGB1, VRK1, AURKA, PADI4, and SRP19 were positively correlated with the level of anti-dsDNA in SLE patients. Comprehensive autoAb screening has identified novel autoAbs, which may shed light on potential pathogenic pathways leading to lupus. Keywords: Systemic lupus erythematosus, Autoantibodies, ProtoArray, Apoptosis, DNA repairhttp://www.sciencedirect.com/science/article/pii/S167202291930124X |
| spellingShingle | Hui Luo Ling Wang Ding Bao Li Wang Hongjun Zhao Yun Lian Mei Yan Chandra Mohan Quan-Zhen Li Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus Genomics, Proteomics & Bioinformatics |
| title | Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus |
| title_full | Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus |
| title_fullStr | Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus |
| title_full_unstemmed | Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus |
| title_short | Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus |
| title_sort | novel autoantibodies related to cell death and dna repair pathways in systemic lupus erythematosus |
| url | http://www.sciencedirect.com/science/article/pii/S167202291930124X |
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