Serum metabolomics analysis of deficiency pattern and excess pattern in patients with rheumatoid arthritis

Abstract

Background Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease. Deficiency pattern (DP) and excess pattern (EP), as crucial types of Chinese medicine pattern diagnoses published by International Classification of Diseases 11th Revision (ICD-11), could provide new strategies for RA diagnosis. However, the biological basis of DP and EP of RA is not explicit. Methods 19 female RA DP patients, 41 female RA EP patients and 30 female healthy participants were included in the study. The serums of participants were collected and analyzed by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to profile metabolic characteristics of RA DP and EP. Furthermore, bioinformatics analysis results were obtained by using Ingenuity Pathway Analysis (IPA) and statistical analysis was performed by SAS version 9.4 for further identification of potential biomarkers. Results Serum metabolic profiling revealed 25 and 24 differential metabolites in RA DP and EP respectively, and 19 metabolites were common to RA DP and EP. Compared with DP group, L-Homocysteic acid, LysoPE(P-16:0/0:0), N(omega)-Hydroxyarginine and LysoPC(16:0/0:0) decreased (P < 0.05), and Pyruvic acid, D-Ribose, Gamma-Glutamylserine, PE(22:0/24:1(15Z)), Inosinic acid increased (P < 0.05) in EP group. Menawhile, S-Nitrosoglutathione, 5-Thymidylic acid, SN38 glucuronide, PE(22:0/24:0), PC(24:0/24:1(15Z)) and Bisdiphosphoinositol tetrakisphosphate increased significantly in DP group compared to EP group (P < 0.05). For the unique metabolites, bioinformatics analysis results showed that 5-Methoxytryptamine involved in Melatonin Degradation II and Superpathway of Melatonin Degradation is the key metabolite to RA DP. Meanwhile, GABA is the key metabolite in EP group, which involved in Glutamate Dependent Acid Resistance, GABA Receptor Signaling, Glutamate Degradation III (via 4-aminobutyrate) and 4-aminobutyrate Degradation I. Bioinformatics analysis between unique metabolites of RA DP and EP groups with human target genes for RA showed that 5-methoxytryptamine and LysoPC(18:1(9Z)/0:0), the unique metabolites of RA DP, might participate in colorectal cancer metastasis signaling, tumor microenvironment pathway, apoptosis signaling, MYC mediated apoptosis signaling, erythropoietin signaling pathway and LXR/RXR activation. Simultaneously, GABA, LysoPA(18:1(9Z)/0:0) and L-Targinine, the unique metabolites of RA EP, might participate in neuroinflammation signaling pathway, osteoarthritis pathway, glucocorticoid receptor signaling, ILK signaling, IL-17 signaling and HIF1α signaling. Conclusions The study indicates that serum metabolomics preliminarily revealed the biological basis of RA DP and EP. 5-methoxytryptamine, LysoPC(18:1(9Z)/0:0) and GABA, LysoPA(18:1(9Z)/0:0), L-Targinine might be the predictors to distinguish the DP and EP of RA respectively. These interesting results provide thoughts for further study of traditional medicine patterns of ICD-11. It also contributes to provide strategy for personalized precision treatment of RA and further validation is needed.

Enhanced protective effect of selenium-biofortified peptide RYNA(Se)MNDYT compared with its native peptide RYNAMNDYT in LPS-injured murine gut microbiota

“…Allantoin has been regarded as a sensitive biomarker for inflammation in inflammatory bowel disease [50,51]. LysoPA(18:1(9Z)/0:0) may participate in the neuroinflammation signaling pathway [52]. Additionally, the biosynthesis of valine, leucine, isoleucine, phenylalanine, tyrosine, and tryptophan and the metabolism of phenylalanine were the most relevant metabolic pathways involved in the protective effect of Se-P2.…”

“…Mobile phase B was 80% acetonitrile with 0.1% formic acid. An elution gradient ((0-50) min, (5-38)% B; (50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60) min, (38-100)% B) was employed on an analytical column (50 μm×15 cm C18-3 μm 100 Å). Data were acquired using an ion spray voltage of 1.9 kV and an interface heater temperature of 275 ℃.…”

Mechanism of Jinteng Qingbi granules in the treatment of rheumatoid arthritis using metabolomics analysis

“…These factors suggest that cytokine‐mediated inflammatory processes play an important role in the progression of RA and that such inflammatory processes can cause metabolic changes. Metabolic pathways have profound effects on the development of unicellular and multicellular organisms (Liu et al, 2022). Metabolites affect immune system development through mechanisms such as antigen receptors and costimulatory molecules, growth factors, hormones, cytokines, environmental factors, and other regulatory signals (Agnihotri et al, 2021; Wang et al, 2021).…”

Meta-analysis of risk factors for cardiovascular disease in patients with rheumatoid arthritis

“…[21] The risk of CHD in high cholesterol groups was 1.7 times higher than in the control group, and the risk in the hypertension group is 3.58 times higher than in the control group, which were consistent with previous reports. Chunlai Zhang [3] 2012 Case control 53 126 1,2,4,28,5,7 6 Weiping Ci [4] 2016 Case control 76 60 22,11,25,36 7 Xuelian Xu [5] 2020 Case control 61 105 7,8,2,5 6 Hongbin Li [6] 2006 Case control 92 476 1,4,28,5 7 Lei Chen [7] 2019 Case control 78 122 13,.7,1,6,5,3,2 7 Tingting Lyu [8] 2016 Case control 62 60 1,5,7,15 7 Yanfang Meng [9] 2019 Case control 50 50 2,5,7 6 Yan Lin [10] 2015 Case control 49 48 14,15,10,11,13,9,20 7 Tanaka [11] 2016 Cohort study 2472 6186 20 6 Crowson [12] 2018 Cohort study 389 5249 37,20,8,23,24,11 7 Ajeganova [13] 2013 Cohort study 177 564 29,31,32,33,34,35 7 Radovits [14] 2008 Cohort study 41 181 38,37 7 Scott [15] 2012 Case control 27 282 9,22,11 7 Serelis [16] 2011 Cohort study 13 174 11,21,26,30 7 Assous [17] 2007 Cohort study 17 239 20,37,7,11,18 7 Chun Li [18] 2017 Case control 256 2013 11,9,17,25 7 Wenjun Lu [19] 2017 Case control 42 84 27,15,8, Triglycerides, age, sex, blood sugar and other risk factors were not included in the final meta-analysis due to the lack of literature.…”