TY - JOUR
T1 - Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus
AU - Luo, Hui
AU - Wang, Ling
AU - Bao, Ding
AU - Wang, Li
AU - Zhao, Hongjun
AU - Lian, Yun
AU - Yan, Mei
AU - Mohan, Chandra
AU - Li, Quan Zhen
N1 - Funding Information:
The authors acknowledge the participants and the staff in Division of Rheumatology, Xiangya Hospital for collecting the samples for this study. This work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81671621 and 81270852 ).
Funding Information:
The authors acknowledge the participants and the staff in Division of Rheumatology, Xiangya Hospital for collecting the samples for this study. This work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81671621 and 81270852).
Publisher Copyright:
© 2019 The Authors
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Autoantibodies
KW - DNA repair
KW - ProtoArray
KW - Systemic lupus erythematosus
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U2 - 10.1016/j.gpb.2018.11.004
DO - 10.1016/j.gpb.2018.11.004
M3 - Article
C2 - 31494269
AN - SCOPUS:85072326111
SN - 1672-0229
VL - 17
SP - 248
EP - 259
JO - Genomics Proteomics Bioinformatics
JF - Genomics Proteomics Bioinformatics
IS - 3
ER -