Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Traditional Chinese Medicine of Rheumatoid Arthritis Using Protein Chips

Heru Zhao; Yin Zhang; Bin Liu; Li Li; Lulu Zhang; Mei Bao; Hongtao Guo; Haiyu Xu; Hui Feng; Lianbo Xiao; Wenjun Yi; Jianfeng Yi; Peng Chen; Cheng Lu; Aiping  Lu

doi:10.3389/fphar.2019.00755

Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Traditional Chinese Medicine of Rheumatoid Arthritis Using Protein Chips

Heru Zhao, Yin Zhang, Bin Liu, Li Li, Lulu Zhang, Mei Bao, Hongtao Guo, Haiyu Xu, Hui Feng, Lianbo Xiao, Wenjun Yi, Jianfeng Yi^*, Peng Chen^*, Cheng Lu^*, Aiping Lu^*

^*Corresponding author for this work

Institute for Advancing Translational Medicine in Bone and Joint Diseases

Research output: Contribution to journal › Journal article › peer-review

7 Citations (Scopus)

Abstract

Background:

Rheumatoid arthritis (RA) is an autoimmune disease. Based on traditional Chinese medicine (TCM) theory, deficiency pattern (DP) which leads to specific treatment principles in clinical management is a crucial pattern diagnosis among RA patients, and autoantibodies have potential implications in TCM pattern classification. The purpose of this study was to identify specific RA DP-associated autoantibodies.

Methods:

RA DP patients, RA nondeficiency pattern (NDP) patients and healthy controls (HCs) were recruited for this study. Then, clinical data and sera from all subjects were collected. After that, the sera were probed with protein chips, which were constructed by known RA related autoantigens, to screen for DP-associated candidate autoantibodies. Lastly, candidate autoantibodies were validated via enzyme-linked immunosorbent assay (ELISA) and function was evaluated by network analysis.

Results:

Protein chips results showed that RA patients have higher levels of anti-vascular endothelial growth factor (VEGF) A165 antibodies than HC (P < 0.005); anti-VEGFA165 antibodies levels of patients with RA DP were lower than patients with RA NDP (P < 0.05). The results of the ELISA also showed statistically significant differences in anti-VEGFA165 antibodies between the RA and HC group (P < 0.0001); and there were statistically significant differences in anti-VEGFA165 antibodies between the RA DP and RA NDP group (P < 0.05). Network analysis results suggested IL-6 signaling pathway has a significant effect on VEGFA165 in RA patients.

Conclusion:

Autoantibodies identification in RA using protein chips help in understanding DP in TCM. Discovery of anti-VEGFA165 antibodies may provide the possibility for clinical precision treatment.

Original language	English
Article number	755
Journal	Frontiers in Pharmacology
Volume	10
DOIs	https://doi.org/10.3389/fphar.2019.00755
Publication status	Published - 10 Jul 2019

Scopus Subject Areas

Pharmacology
Pharmacology (medical)

User-Defined Keywords

autoantibody
autoimmune disease
deficiency pattern
protein chips
rheumatoid arthritis
vascular endothelial growth factor A165

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10.3389/fphar.2019.00755

Cite this

Zhao, H., Zhang, Y., Liu, B., Li, L., Zhang, L., Bao, M., Guo, H., Xu, H., Feng, H., Xiao, L., Yi, W., Yi, J., Chen, P., Lu, C., & Lu, A. (2019). Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Traditional Chinese Medicine of Rheumatoid Arthritis Using Protein Chips. Frontiers in Pharmacology, 10, Article 755. https://doi.org/10.3389/fphar.2019.00755

@article{f9b703301e6b4ebcb610a0c447146424,

title = "Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Traditional Chinese Medicine of Rheumatoid Arthritis Using Protein Chips",

abstract = "Background: Rheumatoid arthritis (RA) is an autoimmune disease. Based on traditional Chinese medicine (TCM) theory, deficiency pattern (DP) which leads to specific treatment principles in clinical management is a crucial pattern diagnosis among RA patients, and autoantibodies have potential implications in TCM pattern classification. The purpose of this study was to identify specific RA DP-associated autoantibodies. Methods: RA DP patients, RA nondeficiency pattern (NDP) patients and healthy controls (HCs) were recruited for this study. Then, clinical data and sera from all subjects were collected. After that, the sera were probed with protein chips, which were constructed by known RA related autoantigens, to screen for DP-associated candidate autoantibodies. Lastly, candidate autoantibodies were validated via enzyme-linked immunosorbent assay (ELISA) and function was evaluated by network analysis. Results: Protein chips results showed that RA patients have higher levels of anti-vascular endothelial growth factor (VEGF) A165 antibodies than HC (P < 0.005); anti-VEGFA165 antibodies levels of patients with RA DP were lower than patients with RA NDP (P < 0.05). The results of the ELISA also showed statistically significant differences in anti-VEGFA165 antibodies between the RA and HC group (P < 0.0001); and there were statistically significant differences in anti-VEGFA165 antibodies between the RA DP and RA NDP group (P < 0.05). Network analysis results suggested IL-6 signaling pathway has a significant effect on VEGFA165 in RA patients. Conclusion: Autoantibodies identification in RA using protein chips help in understanding DP in TCM. Discovery of anti-VEGFA165 antibodies may provide the possibility for clinical precision treatment.",

keywords = "autoantibody, autoimmune disease, deficiency pattern, protein chips, rheumatoid arthritis, vascular endothelial growth factor A165",

author = "Heru Zhao and Yin Zhang and Bin Liu and Li Li and Lulu Zhang and Mei Bao and Hongtao Guo and Haiyu Xu and Hui Feng and Lianbo Xiao and Wenjun Yi and Jianfeng Yi and Peng Chen and Cheng Lu and Aiping Lu",

note = "Funding Information: This study was supported by grants from the Fundamental Research Funds for the Central public welfare research institutes (ZZ11-113, ZZ11-056) and National Natural Science Foundation of China (grant no. 81403209). Publisher copyright: {\textcopyright} 2019 Zhao, Zhang, Liu, Li, Zhang, Bao, Guo, Xu, Feng, Xiao, Yi, Yi, Chen, Lu and Lu. ",

year = "2019",

month = jul,

day = "10",

doi = "10.3389/fphar.2019.00755",

language = "English",

volume = "10",

journal = "Frontiers in Pharmacology",

issn = "1663-9812",

publisher = "Frontiers Media S.A.",

}

Zhao, H, Zhang, Y, Liu, B, Li, L, Zhang, L, Bao, M, Guo, H, Xu, H, Feng, H, Xiao, L, Yi, W, Yi, J, Chen, P, Lu, C & Lu, A 2019, 'Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Traditional Chinese Medicine of Rheumatoid Arthritis Using Protein Chips', Frontiers in Pharmacology, vol. 10, 755. https://doi.org/10.3389/fphar.2019.00755

TY - JOUR

T1 - Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Traditional Chinese Medicine of Rheumatoid Arthritis Using Protein Chips

AU - Zhao, Heru

AU - Zhang, Yin

AU - Liu, Bin

AU - Li, Li

AU - Zhang, Lulu

AU - Bao, Mei

AU - Guo, Hongtao

AU - Xu, Haiyu

AU - Feng, Hui

AU - Xiao, Lianbo

AU - Yi, Wenjun

AU - Yi, Jianfeng

AU - Chen, Peng

AU - Lu, Cheng

AU - Lu, Aiping

N1 - Funding Information: This study was supported by grants from the Fundamental Research Funds for the Central public welfare research institutes (ZZ11-113, ZZ11-056) and National Natural Science Foundation of China (grant no. 81403209). Publisher copyright: © 2019 Zhao, Zhang, Liu, Li, Zhang, Bao, Guo, Xu, Feng, Xiao, Yi, Yi, Chen, Lu and Lu.

PY - 2019/7/10

Y1 - 2019/7/10

N2 - Background: Rheumatoid arthritis (RA) is an autoimmune disease. Based on traditional Chinese medicine (TCM) theory, deficiency pattern (DP) which leads to specific treatment principles in clinical management is a crucial pattern diagnosis among RA patients, and autoantibodies have potential implications in TCM pattern classification. The purpose of this study was to identify specific RA DP-associated autoantibodies. Methods: RA DP patients, RA nondeficiency pattern (NDP) patients and healthy controls (HCs) were recruited for this study. Then, clinical data and sera from all subjects were collected. After that, the sera were probed with protein chips, which were constructed by known RA related autoantigens, to screen for DP-associated candidate autoantibodies. Lastly, candidate autoantibodies were validated via enzyme-linked immunosorbent assay (ELISA) and function was evaluated by network analysis. Results: Protein chips results showed that RA patients have higher levels of anti-vascular endothelial growth factor (VEGF) A165 antibodies than HC (P < 0.005); anti-VEGFA165 antibodies levels of patients with RA DP were lower than patients with RA NDP (P < 0.05). The results of the ELISA also showed statistically significant differences in anti-VEGFA165 antibodies between the RA and HC group (P < 0.0001); and there were statistically significant differences in anti-VEGFA165 antibodies between the RA DP and RA NDP group (P < 0.05). Network analysis results suggested IL-6 signaling pathway has a significant effect on VEGFA165 in RA patients. Conclusion: Autoantibodies identification in RA using protein chips help in understanding DP in TCM. Discovery of anti-VEGFA165 antibodies may provide the possibility for clinical precision treatment.

AB - Background: Rheumatoid arthritis (RA) is an autoimmune disease. Based on traditional Chinese medicine (TCM) theory, deficiency pattern (DP) which leads to specific treatment principles in clinical management is a crucial pattern diagnosis among RA patients, and autoantibodies have potential implications in TCM pattern classification. The purpose of this study was to identify specific RA DP-associated autoantibodies. Methods: RA DP patients, RA nondeficiency pattern (NDP) patients and healthy controls (HCs) were recruited for this study. Then, clinical data and sera from all subjects were collected. After that, the sera were probed with protein chips, which were constructed by known RA related autoantigens, to screen for DP-associated candidate autoantibodies. Lastly, candidate autoantibodies were validated via enzyme-linked immunosorbent assay (ELISA) and function was evaluated by network analysis. Results: Protein chips results showed that RA patients have higher levels of anti-vascular endothelial growth factor (VEGF) A165 antibodies than HC (P < 0.005); anti-VEGFA165 antibodies levels of patients with RA DP were lower than patients with RA NDP (P < 0.05). The results of the ELISA also showed statistically significant differences in anti-VEGFA165 antibodies between the RA and HC group (P < 0.0001); and there were statistically significant differences in anti-VEGFA165 antibodies between the RA DP and RA NDP group (P < 0.05). Network analysis results suggested IL-6 signaling pathway has a significant effect on VEGFA165 in RA patients. Conclusion: Autoantibodies identification in RA using protein chips help in understanding DP in TCM. Discovery of anti-VEGFA165 antibodies may provide the possibility for clinical precision treatment.

KW - autoantibody

KW - autoimmune disease

KW - deficiency pattern

KW - protein chips

KW - rheumatoid arthritis

KW - vascular endothelial growth factor A165

UR - http://www.scopus.com/inward/record.url?scp=85080977046&partnerID=8YFLogxK

U2 - 10.3389/fphar.2019.00755

DO - 10.3389/fphar.2019.00755

M3 - Journal article

AN - SCOPUS:85080977046

SN - 1663-9812

VL - 10

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 755

ER -

Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Traditional Chinese Medicine of Rheumatoid Arthritis Using Protein Chips

Abstract

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