Inorganic pyrophosphatase 1: a key player in immune and metabolic reprogramming in ankylosing spondylitis

Inorganic pyrophosphatase 1: a key player in immune and metabolic reprogramming in ankylosing spondylitis


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ABSTRACT The relationships among immune cells, metabolites, and AS events were analyzed via Mendelian randomization (MR), and potential immune cells and metabolites were identified as risk


factors for AS. Their relationships were subjected to intermediary MR analysis to identify the final immune cells and metabolites. The vertebral bone marrow blood samples from three patients


with and without AS were subjected to 10× single-cell sequencing to further elucidate the role of immune cells in AS. The key genes were screened via expression quantitative trait loci


(eQTLs) and MR analyses. The metabolic differences between the two groups were compared through single-cell metabolism analysis. Two subgroups of differentiated (CD)8+ memory T cells and


naive B cells were obtained from the combined results of intermediary MR analysis and AS single-cell analysis. After the verification of key genes, inorganic pyrophosphatase 1 (PPA1) was


identified as the hub gene, as it is differentially expressed in CD8+ memory T cells and can affect the metabolism of T cells in AS by affecting the expression of ferulic acid (FA)4 sulfate,


which participates in the cellular immunity in AS. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS


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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE SHARED ROLE OF NEUTROPHILS IN ANKYLOSING SPONDYLITIS AND ULCERATIVE COLITIS


Article 25 July 2024 ANALYSIS OF M6A REGULATORS RELATED IMMUNE CHARACTERISTICS IN ANKYLOSING SPONDYLITIS BY INTEGRATED BIOINFORMATICS AND COMPUTATIONAL STRATEGIES Article Open access 01


February 2024 SINGLE-CELL RNA SEQUENCING REVEALS MULTIPLE IMMUNE CELL SUBPOPULATIONS PROMOTE THE FORMATION OF ABNORMAL BONE MICROENVIRONMENT IN OSTEOPOROSIS Article Open access 27 November


2024 DATA AVAILABILITY The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. REFERENCES * Drosos AA,


Venetsanopoulou AI, Voulgari PV. Axial Spondyloarthritis: Evolving concepts regarding the disease’s diagnosis and treatment. Eur J Intern Med. 2023;117:21–7.


https://doi.org/10.1016/j.ejim.2023.06.026. Article  CAS  PubMed  Google Scholar  * McGonagle D, Ramonda R, Scagnellato L, Scriffignano S, Weddell J, Lubrano E. A strategy towards


disentangling treatment refractory from misdiagnosed axial Spondyloarthritis. Autoimmun Rev. 2024;23(1):103405. https://doi.org/10.1016/j.autrev.2023.103405. Article  PubMed  Google Scholar


  * Barnett R, Gaffney K, Sengupta R. Diagnostic delay in axial spondylarthritis: A lost battle? Best Pract Res Clin Rheumatol. 2023;37(3):101870. https://doi.org/10.1016/j.berh.2023.101870.


Article  PubMed  Google Scholar  * van Gaalen FA, Rudwaleit M. Challenges in the diagnosis of axial spondyloarthritis. Best Pract Res Clin Rheumatol. 2023;37(3):101871.


https://doi.org/10.1016/j.berh.2023.101871. Article  PubMed  Google Scholar  * Xie J, Xu J, Chen H. Regulatory mechanisms of miR-212-3p on the secretion of inflammatory factors in


monocyte-macrophages and the directed differentiation into osteoclasts in ankylosing spondylitis. Aging. 2023;15(22):13411–21. https://doi.org/10.18632/aging.205249. Article  CAS  PubMed 


PubMed Central  Google Scholar  * Feng X, Wang C, Ji B, Qiao J, Xu Y, Zhu S, et al. CD_99 G1 neutrophils modulate osteogenic differentiation of mesenchymal stem cells in the pathological


process of ankylosing spondylitis. Ann Rheum Dis. 2024;83(3):324–34. https://doi.org/10.1136/ard-2023-224107. Article  CAS  PubMed  Google Scholar  * Komech EA, Koltakova AD, Barinova AA,


Minervina AA, Salnikova MA, Shmidt EI, et al. TCR repertoire profiling revealed antigen-driven CD8+ T cell clonal groups shared in synovial fluid of patients with spondyloarthritis. Front


Immunol. 2022;13:973243. https://doi.org/10.3389/fimmu.2022.973243. Article  CAS  PubMed  PubMed Central  Google Scholar  * Garrido-Mesa J, Brown MA. T cell repertoire profiling and the


mechanism by which HLA-B27 causes ankylosing spondylitis. Curr Rheumatol Rep. 2022;24(12):398–4. https://doi.org/10.1007/s11926-022-01090-6. Article  CAS  PubMed  PubMed Central  Google


Scholar  * Rosine N, Fogel O, Koturan S, Rogge L, Bianchi E, Miceli-Richard C. T cells in the pathogenesis of axial spondyloarthritis. J Bone Spine. 2023;90(6):105619.


https://doi.org/10.1016/j.jbspin.2023.105619. Article  CAS  Google Scholar  * Wilbrink R, Spoorenberg A, Verstappen G, Kroese FGM. B cell involvement in the pathogenesis of ankylosing


spondylitis. Int J Mol Sci. 2021;22(24):13325. https://doi.org/10.3390/ijms222413325. Article  CAS  PubMed  PubMed Central  Google Scholar  * Wang S, Yang N, Zhang H. Metabolic dysregulation


of lymphocytes in autoimmune diseases. Trends Endocrinol Metab: TEM. 2024;35(7):624–37. https://doi.org/10.1016/j.tem.2024.01.005. Article  CAS  PubMed  Google Scholar  * Wang PF, Jiang F,


Zeng QM, Yin WF, Hu YZ, Li Q, et al. Mitochondrial and metabolic dysfunction of peripheral immune cells in multiple sclerosis. J Neuroinflammation. 2024;21(1):28.


https://doi.org/10.1186/s12974-024-03016-8. Article  PubMed  PubMed Central  Google Scholar  * Li J, Zhao M, Luo W, Huang J, Zhao B, Zhou Z. B cell metabolism in autoimmune diseases:


signaling pathways and interventions. Front Immunol. 2023;14:1232820. https://doi.org/10.3389/fimmu.2023.1232820. Article  CAS  PubMed  PubMed Central  Google Scholar  * Mora VP, Loaiza RA,


Soto JA, Bohmwald K, Kalergis AM. Involvement of trained immunity during autoimmune responses. J Autoimmun. 2023;137:102956. https://doi.org/10.1016/j.jaut.2022.102956. Article  CAS  PubMed


  Google Scholar  * Xu Y, Chen Y, Zhang X, Ma J, Liu Y, Cui L, et al. Glycolysis in innate immune cells contributes to autoimmunity. Front Immunol. 2022;13:920029.


https://doi.org/10.3389/fimmu.2022.920029. Article  CAS  PubMed  PubMed Central  Google Scholar  * Hu JQ, Yan YH, Xie H, Feng XB, Ge WH, Zhou H, et al. Targeting abnormal lipid metabolism of


T cells for systemic lupus erythematosus treatment. Biomed Pharmacother = Biomedecine Pharmacotherapie. 2023;165:115198. https://doi.org/10.1016/j.biopha.2023.115198. Article  CAS  PubMed 


Google Scholar  * Gan PR, Wu H, Zhu YL, Shu Y, Wei Y. Glycolysis, a driving force of rheumatoid arthritis. Int Immunopharmacol. 2024;132:111913. https://doi.org/10.1016/j.intimp.2024.111913.


Article  CAS  PubMed  Google Scholar  * Ferreté-Bonastre AG, Martínez-Gallo M, Morante-Palacios O, Calvillo CL, Calafell-Segura J, Rodríguez-Ubreva J, et al. Disease activity drives


divergent epigenetic and transcriptomic reprogramming of monocyte subpopulations in systemic lupus erythematosus. Ann Rheum Dis. 2024;83(7):865–78. https://doi.org/10.1136/ard-2023-225433.


Article  CAS  PubMed  Google Scholar  * Fu JY, Huang SJ, Wang BL, Yin JH, Chen CY, Xu JB, et al. Lysine acetyltransferase 6A maintains CD4(+) T cell response via epigenetic reprogramming of


glucose metabolism in autoimmunity. Cell Metab. 2024;36(3):557–74.e. https://doi.org/10.1016/j.cmet.2023.12.016. Article  CAS  PubMed  Google Scholar  * Cribbs AP, Terlecki-Zaniewicz S,


Philpott M, Baardman J, Ahern D, Lindow M, et al. Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism. Proc Natl Acad Sci


USA. 2020;117(11):6056–66. https://doi.org/10.1073/pnas.1919893117. Article  CAS  PubMed  PubMed Central  Google Scholar  * Chen Y, Song J, Ruan Q, Zeng X, Wu L, Cai L, et al. Single-cell


sequencing methodologies: from transcriptome to multi-dimensional measurement. Small Methods. 2021;5(6):e2100111. https://doi.org/10.1002/smtd.202100111. Article  CAS  PubMed  Google Scholar


  * Chen C, Wang P, Zhang RD, Fang Y, Jiang LQ, Fang X, et al. Mendelian randomization as a tool to gain insights into the mosaic causes of autoimmune diseases. Autoimmun Rev.


2022;21(12):1032. https://doi.org/10.1016/j.autrev.2022.103210. Article  CAS  Google Scholar  * Zhou C, Liang T, Jiang J, Zhang Z, Chen J, Chen T, et al. Immune cell infiltration-related


clinical diagnostic model for Ankylosing Spondylitis. Front Genet. 2022;13:949882. https://doi.org/10.3389/fgene.2022.949882. Article  CAS  PubMed  PubMed Central  Google Scholar  * Chen Y,


Lu T, Pettersson-Kymmer U, Stewart ID, Butler-Laporte G, Nakanishi T, et al. Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases. Nat Genet.


2023;55(1):44–53. https://doi.org/10.1038/s41588-022-01270-1. Article  CAS  PubMed  PubMed Central  Google Scholar  * Orrù V, Steri M, Sidore C, Marongiu M, Serra V, Olla S, et al. Author


Correction: Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet. 2020;52(11):1266. https://doi.org/10.1038/s41588-020-00718-6. Article  CAS  PubMed


  Google Scholar  * Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D..et al. The MR-Base platform supports systematic causal inference across the human phenome. eLife. 2018;7.


https://doi.org/10.7554/eLife.34408. * Mensah-Kane J, Schmidt AF, Hingorani AD, Finan C, Chen Y, van Duijvenboden S, et al. No clinically relevant effect of heart rate increase and heart


rate recovery during exercise on cardiovascular disease: a mendelian randomization analysis. Front Genet. 2021;12:569323. https://doi.org/10.3389/fgene.2021.569323. Article  PubMed  PubMed


Central  Google Scholar  * Greco MF, Minelli C, Sheehan NA, Thompson JR. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med.


2015;34(21):2926–40. https://doi.org/10.1002/sim.6522. Article  Google Scholar  * Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships


inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693–8. https://doi.org/10.1038/s41588-018-0099-7. Article  CAS  PubMed  PubMed Central 


Google Scholar  * Burgess S, Davey Smith G, Davies NM, Dudbridge F, Gill D, Glymour MM, et al. Guidelines for performing Mendelian randomization investigations: update for summer 2023.


Wellcome open Res. 2019;4:186. https://doi.org/10.12688/wellcomeopenres.15555.3. Article  PubMed  Google Scholar  * Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid


instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25. https://doi.org/10.1093/ije/dyv080. Article  PubMed  PubMed Central  Google


Scholar  * Gala H, Tomlinson I. The use of Mendelian randomisation to identify causal cancer risk factors: promise and limitations. J Pathol. 2020;250(5):541–54.


https://doi.org/10.1002/path.5421. Article  PubMed  Google Scholar  * Sanderson E. Multivariable mendelian randomization and mediation. Cold Spring Harbor Persp Medi. 2021;11(2):a038984


https://doi.org/10.1101/cshperspect.a038984. Article  CAS  Google Scholar  * Conesa A, Madrigal P, Tarazona S, Gomez-Cabrero D, Cervera A, McPherson A, et al. A survey of best practices for


RNA-seq data analysis. Genome Biol. 2016;17:13. https://doi.org/10.1186/s13059-016-0881-8. Article  CAS  PubMed  PubMed Central  Google Scholar  * Mauro D, Thomas R, Guggino G, Lories R,


Brown MA, Ciccia F. Ankylosing spondylitis: an autoimmune or autoinflammatory disease? Nat Rev Rheumatol. 2021;17(7):387–404. https://doi.org/10.1038/s41584-021-00625-y. Article  CAS  PubMed


  Google Scholar  * Voruganti A, Bowness P. New developments in our understanding of ankylosing spondylitis pathogenesis. Immunology. 2020;161(2):94–102. https://doi.org/10.1111/imm.13242.


Article  CAS  PubMed  PubMed Central  Google Scholar  * Pedersen SJ, Maksymowych WP. The pathogenesis of ankylosing spondylitis: an update. Curr Rheumatol Rep. 2019;21(10):58.


https://doi.org/10.1007/s11926-019-0856-3. Article  CAS  PubMed  Google Scholar  * McCann C, Kerr EM. Metabolic reprogramming: a friend or foe to cancer therapy?. Cancers. 2021;13(13):3351.


https://doi.org/10.3390/cancers13133351. Article  CAS  PubMed  PubMed Central  Google Scholar  * Sun L, Zhang H, Gao P. Metabolic reprogramming and epigenetic modifications on the path to


cancer. Protein Cell. 2022;13(12):877–919. https://doi.org/10.1007/s13238-021-00846-7. Article  CAS  PubMed  Google Scholar  * Halper-Stromberg A, Jabri B. Maladaptive consequences of


inflammatory events shape individual immune identity. Nat Immunol. 2022;23(12):1675–86. https://doi.org/10.1038/s41590-022-01342-8. Article  CAS  PubMed  Google Scholar  * Chou WC,


Rampanelli E, Li X, Ting JP. Impact of intracellular innate immune receptors on immunometabolism. Cell Mol Immunol. 2022;19(3):337–51. https://doi.org/10.1038/s41423-021-00780-y. Article 


CAS  PubMed  Google Scholar  * Raniga K, Liang C. Interferons: Reprogramming the metabolic network against viral infection. Viruses. 2018;10(1):36. https://doi.org/10.3390/v10010036. *


Thimmappa PY, Vasishta S, Ganesh K, Nair AS, Joshi MB. Neutrophil (dys)function due to altered immuno-metabolic axis in type 2 diabetes: implications in combating infections. Hum cell.


2023;36(4):1265–82. https://doi.org/10.1007/s13577-023-00905-7. Article  CAS  PubMed  PubMed Central  Google Scholar  * Marrocco A, Ortiz LA. Role of metabolic reprogramming in


pro-inflammatory cytokine secretion from LPS or silica-activated macrophages. Front Immunol. 2022;13:936167. https://doi.org/10.3389/fimmu.2022.936167. Article  CAS  PubMed  PubMed Central 


Google Scholar  * Li F, Liu H, Zhang D, Ma Y, Zhu B. Metabolic plasticity and regulation of T cell exhaustion. Immunology. 2022;167(4):482–94. https://doi.org/10.1111/imm.13575. Article  CAS


  PubMed  Google Scholar  * Guimarães ES, Marinho FV, de Queiroz N, Antunes MM, Oliveira SC. Impact of STING Inflammatory Signaling during Intracellular Bacterial Infections. Cells.


2021;11(1):74. https://doi.org/10.3390/cells11010074. * Sekula P, Del Greco MF, Pattaro C, Köttgen A. Mendelian randomization as an approach to assess causality using observational data. J


Am Soc Nephrol. 2016;27(11):3253–65. https://doi.org/10.1681/asn.2016010098. Article  PubMed  PubMed Central  Google Scholar  * Zhang Y, Wang J, Yu C, Xia K, Yang B, Zhang Y, et al. Advances


in single-cell sequencing and its application to musculoskeletal system research. Cell Prolif. 2022;55(1):e13161. https://doi.org/10.1111/cpr.13161. Article  CAS  PubMed  Google Scholar  *


Yang P, Huang H, Liu C. Feature selection revisited in the single-cell era. Genome Biol. 2021;22(1):321 https://doi.org/10.1186/s13059-021-02544-3. Article  PubMed  PubMed Central  Google


Scholar  * Barreiro-Sisto U, Fernández-Fariña S, González-Noya AM, Pedrido R, Maneiro M. Enemies or Allies? Hormetic and apparent non-dose-dependent effects of natural bioactive antioxidants


in the treatment of inflammation. Int J Mol Sci 2024;25(3):1892. https://doi.org/10.3390/ijms25031892. * Wu J, Zhou F, Fan G, Liu J, Wang Y, Xue X, et al. Ferulic acid ameliorates


acetaminophen-induced acute liver injury by promoting AMPK-mediated protective autophagy. IUBMB life. 2022;74(9):880–95. https://doi.org/10.1002/iub.2625. Article  CAS  PubMed  Google


Scholar  * Wu J, Xue X, Fan G, Gu Y, Zhou F, Zheng Q, et al. Ferulic acid ameliorates hepatic inflammation and fibrotic liver injury by inhibiting PTP1B activity and subsequent promoting


AMPK phosphorylation. Front Pharmacol. 2021;12:754976. https://doi.org/10.3389/fphar.2021.754976. Article  CAS  PubMed  PubMed Central  Google Scholar  * Ye L, Hu P, Feng LP, Huang LL, Wang


Y, Yan X, et al. Protective effects of ferulic acid on metabolic syndrome: a comprehensive review. Molecules (Basel, Switzerland). 2022;28(1):281. https://doi.org/10.3390/molecules28010281.


* Li Y, Sair AT, Zhao W, Li T, Liu RH. Ferulic acid mediates metabolic syndrome via the regulation of hepatic glucose and lipid metabolisms and the insulin/IGF-1 rReceptor/PI3K/AKT pathway


in palmitate-treated HepG2 cells. J Agric food Chem. 2022;70(46):14706–17. https://doi.org/10.1021/acs.jafc.2c05676. Article  CAS  PubMed  Google Scholar  * Sun L, Yang Z, Zhao W, Chen Q,


Bai H, Wang S, et al. Integrated lipidomics, transcriptomics and network pharmacology analysis to reveal the mechanisms of Danggui Buxue Decoction in the treatment of diabetic nephropathy in


type 2 diabetes mellitus. J Ethnopharmacol. 2022;283:114699. https://doi.org/10.1016/j.jep.2021.114699. Article  CAS  PubMed  Google Scholar  * Hammad SM, Lopes-Virella MF. Circulating


sphingolipids in insulin resistance, diabetes and associated complications. Int J Mol Sci. 2023;24(18):14015. https://doi.org/10.3390/ijms241814015. * Naquet P, Kerr EW, Vickers SD, Leonardi


R. Regulation of coenzyme A levels by degradation: the ‘Ins and Outs’. Prog lipid Res. 2020;78:101028. https://doi.org/10.1016/j.plipres.2020.101028. Article  CAS  PubMed  PubMed Central 


Google Scholar  * Yin Y, Wu Y, Zhang X, Zhu Y, Sun Y, Yu J, et al. PPA1 regulates systemic insulin sensitivity by maintaining adipocyte mitochondria function as a novel PPARγ Target Gene.


Diabetes. 2021;70(6):1278–91. https://doi.org/10.2337/db20-0622. Article  CAS  PubMed  Google Scholar  * Tavasolian F, Pastrello C, Ahmed Z, Jurisica I, Inman RD. Vesicular traffic-mediated


cell-to-cell signaling at the immune synapse in Ankylosing Spondylitis. Front Immunol. 2022;13:1102405. https://doi.org/10.3389/fimmu.2022.1102405. Article  CAS  PubMed  Google Scholar  *


Liu L, Yuan Y, Zhang S, Xu J, Zou J. Osteoimmunological insights into the pathogenesis of ankylosing spondylitis. J Cell Physiol. 2021;236(9):6090–100. https://doi.org/10.1002/jcp.30313.


Article  CAS  PubMed  Google Scholar  * Tam HKJ, Robinson PC, Nash P. Inhibiting IL-17A and IL-17F in rheumatic disease: therapeutics help to elucidate disease mechanisms. Curr Rheumatol


Rep. 2022;24(10):310–20. https://doi.org/10.1007/s11926-022-01084-4. Article  CAS  PubMed  PubMed Central  Google Scholar  * Gracey E, Yao Y, Qaiyum Z, Lim M, Tang M, Inman RD. Altered


cytotoxicity profile of CD8+ T cells in ankylosing spondylitis. Arthritis Rheumatol. 2020;72(3):428–34. https://doi.org/10.1002/art.41129. Article  CAS  PubMed  Google Scholar  * Zhang L,


Jarvis LB, Baek HJ, Gaston JS. Regulatory IL4+CD8+ T cells in patients with ankylosing spondylitis and healthy controls. Ann Rheum Dis. 2009;68(8):1345–51.


https://doi.org/10.1136/ard.2008.088120. Article  CAS  PubMed  Google Scholar  * Vecellio M, Cohen CJ, Roberts AR, Wordsworth PB, Kenna TJ. RUNX3 and T-bet in immunopathogenesis of


ankylosing spondylitis-novel targets for therapy? Front Immunol. 2018;9:3132. https://doi.org/10.3389/fimmu.2018.03132. Article  CAS  PubMed  Google Scholar  * Pedersen SJ, Maksymowych WP.


Beyond the TNF-α inhibitors: new and emerging targeted therapies for patients with axial spondyloarthritis and their relation to pathophysiology. Drugs. 2018;78(14):1397–418.


https://doi.org/10.1007/s40265-018-0971-x. Article  CAS  PubMed  Google Scholar  * Sun Y, Yao J, Lu C, Yang N, Han X, Lin H, et al. Cold-inducible PPA1 is critical for the adipocyte browning


in mice. Biochem Biophys Res Commun. 2023;677:45–53. https://doi.org/10.1016/j.bbrc.2023.08.009. Article  CAS  PubMed  Google Scholar  * Khan MA. HLA-B*27 and ankylosing spondylitis: 50


years of insights and discoveries. Curr Rheumatol Rep. 2023;25(12):327–40. https://doi.org/10.1007/s11926-023-01118-5. Article  CAS  PubMed  Google Scholar  * Braun J, Sieper J. Fifty years


after the discovery of the association of HLA B27 with ankylosing spondylitis. RMD Open. 2023;9(3):e003102. https://doi.org/10.1136/rmdopen-2023-003102. * Brown EM, Nguyen PNU, Xavier RJ.


Emerging biochemical, microbial and immunological evidence in the search for why HLA-B∗27 confers risk for spondyloarthritis. Cell Chem Biol. 2024;20:S2451-9456(24)00314-3.


https://doi.org/10.1016/j.chembiol.2024.07.012. * Paley MA, Yang X, Hassman LM, Penkava F, Garner LI, Paley GL, et al. Mucosal signatures of pathogenic T cells in HLA-B*27+ anterior uveitis


and axial spondyloarthritis. JCI insight. 2024;9(16)e174776. https://doi.org/10.1172/jci.insight.174776. Download references FUNDING This study was supported by the National Natural Science


Foundation of China(Grant/Award number: 8236090175), Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation (Grant/Award number: 2023JJA140227), The


“Medical Excellence Award” Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University, and Guangxi Young and Middle aged Teacher’s


Basic Ability Promoting Project(Grant/Award Number: 2023KY0115). AUTHOR INFORMATION Author notes * These authors contributed equally: Tianyou Chen, Chengqian Huang. AUTHORS AND AFFILIATIONS


* The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China Tianyou Chen, Chengqian Huang, Jiarui Chen, Jiang


Xue, Zhenwei Yang, Yihan Wang, Songze Wu, Wendi Wei, Liyi Chen, Shian Liao, Xiaopeng Qin, Rongqing He, Boli Qin & Chong Liu Authors * Tianyou Chen View author publications You can also


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Google Scholar CONTRIBUTIONS Conceptualization: Tianyou Chen, Chong Liu; Methodology: Tianyou Chen, Chengqian Huang; Formal analysis and investigation: Jiang Xue; Validation and Writing -


original draft preparation: Jiarui Chen; Writing - review and editing: Tianyou Chen, Chengqian Huang, Chong Liu; Funding acquisition: Chong Liu; Data curation: Zhenwei Yang, Yihan Wang,


Songze Wu; Resources: Wendi Wei, Liyi Chen, Shian Liao; Software: Xiaopeng Qin, Rongqing He; Supervision: Chong Liu; Visualization: Boli Qin. CORRESPONDING AUTHOR Correspondence to Chong


Liu. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. CONSENT FOR PUBLICATION All authors are aware of and agree to the publication of this study. ETHICAL


APPROVAL AND CONSENT TO PARTICIPATE The study was approved by the ethics review board of First Affiliated Hospital Of Guangxi Medical University Ethical Review Committee (Approval No.


2024-E205-01) in accordance with the Declaration of Helsinki. All methods were carried out in accordance with relevant guidelines and regulations. Written informed consent was obtained from


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ankylosing spondylitis. _Genes Immun_ 26, 9–21 (2025). https://doi.org/10.1038/s41435-024-00308-0 Download citation * Received: 23 June 2024 * Revised: 22 October 2024 * Accepted: 31 October


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