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

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.