Salivary Metabolites Profiling in Primary Sjögren Syndrome: Identifying Purine as a Potential Biomarker
Main Article Content
Abstract
Background: Salivary biomarkers such as proteins, metabolites, hormones, and nucleic acids can provide biological information for a variety of medical problems, such as cancer, stress, systemic disorders, and neurodegenerative and infectious diseases. The proteome and metabolomic alterations observed in saliva appear to match those observed in blood, reflecting the cells’ cellular activity and physiological status.
Methods: This is a case-control study that included 10 individuals [5 primary Sjögren syndrome (pSS) and 5 healthy controls (HCs)], each contributing two salivary matrices (unstimulated saliva and oral rinse), resulting in a total of 20 samples for metabolomic analysis (n = 20 samples from n = 10 participants). Salivary metabolite profiling was performed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS), with the HMDB, BRMB, and METLIN databases used for metabolite identification. Chemometric analysis (Unscrambler software) and statistical analysis (SPSS) were used to assess the diagnostic potential of the identified metabolites.
Results: LC-Q-TOF-MS identified 269 metabolites, with purine significantly upregulated in pSS patients compared to HCs (P = 0.01). Upregulation of purine metabolism may indicate an inflammatory response in pSS patients.
Conclusion: In this study, we found that there was a significant difference in the salivary metabolites profile (purine) between patients with pSS and HCs; thus, analysing purine metabolites in saliva may serve as a potential non-invasive candidate biomarker that warrants validation in larger cohorts for discriminating between patients with pSS from HCs and monitoring disease progression.
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References
Jonsson R, Vogelsang P, Volchenkov R, Espinosa A, Wahren-Herlenius M, Appel S. The complexity of Sjögren’s syndrome: Novel aspects on pathogenesis. Immunol Lett. 2011;141(1):1–9. https://doi.org/10.1016/j.imlet.2011.06.007
Goules AV, Tzioufas AG. Primary Sjögren’s syndrome: Clinical phenotypes, outcome and the development of biomarkers. Autoimmun Rev. 2016;15(7):695–703. https://doi.org/10.1016/j.autrev.2016.03.004
Chevet B, Chiche L, Devauchelle-Pensec V, Cornec DYK. How rare is primary Sjögren’s syndrome? Joint Bone Spine. 2023;90(1):105480. https://doi.org/10.1016/j.jbspin.2022.105480
Maciel G, Crowson CS, Matteson EL, Cornec D. Prevalence of primary Sjögren’s syndrome in a US population-based cohort. Arthritis Care Res. 2017;69(10):1612–1616. https://doi.org/10.1002/acr.23173
Wang B, Chen S, Zheng Q, Li Y, Zhang X, Xuan J, et al. Early diagnosis and treatment for Sjögren’s syndrome: Current challenges, redefined disease stages and future prospects. J Autoimmun. 2021;117:102590. https://doi.org/10.1016/j.jaut.2020.102590
Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35–45. https://doi.org/10.1002/art.39859
Zhang CZ, Cheng XQ, Li JY, Zhang P, Yi P, Xu X, et al. Saliva in the diagnosis of diseases. Int J Oral Sci. 2016;8:133–137. https://doi.org/10.1038/ijos.2016.38
Alt-Holland A, Huang X, Mendez T, Singh ML, Papas AS, Cimmino J, et al. Identification of salivary metabolic signatures associated with primary Sjögren’s disease. Molecules. 2023;28(15):5891. https://doi.org/10.3390/molecules28155891
Bosman P, Pichon V, Acevedo AC, Modesto FMB, Paula LM, Le Pottier L, et al. Identification of potential salivary biomarkers for Sjögren’s syndrome with an untargeted metabolomic approach. Metabolomics. 2023;19:76. https://doi.org/10.1007/s11306-023-02040-8
Mikkonen J, Herrala M, Soininen P, Lappalainen R, Tjäderhane L, Seitsalo H, et al. Metabolic profiling of saliva in patients with primary Sjögren’s syndrome. Metabolomics. 2013;3(3):128. https://doi.org/10.4172/2153-0769.1000128
Herrala M, Mikkonen JJW, Pesonen P, Lappalainen R, Tjäderhane L, Niemelä RK, et al. Variability of salivary metabolite levels in patients with Sjögren’s syndrome. J Oral Sci. 2020;63(1):22–26. https://doi.org/10.2334/josnusd.19-0504
Kageyama G, Saegusa J, Irino Y, Tanaka S, Tsuda K, Takahashi S, et al. Metabolomics analysis of saliva from patients with primary Sjögren’s syndrome. Clin Exp Immunol. 2015;182(2):149–153. https://doi.org/10.1111/cei.12683
Setti G, Righi V, Mucci A, Panari L, Bernardelli G, Tarentini E, et al. Metabolic profile of whole unstimulated saliva in patients with Sjögren’s syndrome. Metabolites. 2023;13(3):348. https://doi.org/10.3390/metabo13030348
Li Z, Mu Y, Guo C, You X, Liu X, Li Q, et al. Analysis of the saliva metabolic signature in patients with primary Sjögren’s syndrome. PLoS One. 2022;17(6):e0269275. https://doi.org/10.1371/journal.pone.0269275
Das P, Challacombe SJ. Dry mouth and clinical oral dryness scoring systems. Prim Dent J. 2016;5(1):11–15. https://doi.org/10.1177/205016841600500110
Rosli NA, Al-Maleki AR, Loke MF, Tay ST, Rofiee MS, Teh LK, et al. Exposure of Helicobacter pylori to clarithromycin in vitro resulting in the development of resistance and triggers metabolic reprogramming associated with virulence and pathogenicity. PLoS One. 2024;19(3):e0298434. https://doi.org/10.1371/journal.pone.0298434
Figueira J, Gouveia-Figueira S, Öhman C, Lif Holgerson P, Nording ML, Öhman A. Metabolite quantification by NMR and LC-MS/MS reveals differences between unstimulated, stimulated, and pure parotid saliva. J Pharm Biomed Anal. 2017;140:295–300. https://doi.org/10.1016/j.jpba.2017.03.037
Jo R, Nishimoto Y, Umezawa K, Yama K, Aita Y, Ichiba Y, et al. Comparison of oral microbiome profiles in stimulated and unstimulated saliva, tongue, and mouth-rinsed water. Sci Rep. 2019;9(1):16124. https://doi.org/10.1038/s41598-019-52445-6
Maruyama Y, Nishimoto Y, Umezawa K, Kawamata R, Ichiba Y, Tsutsumi K, et al. Comparison of oral metabolome profiles of stimulated saliva, unstimulated saliva, and mouth-rinsed water. Sci Rep. 2022;12:689. https://doi.org/10.1038/s41598-021-04612-x
Takeda I, Stretch C, Barnaby P, Bhatnager K, Rankin K, Fu H, et al. Understanding the human salivary metabolome. NMR Biomed. 2009;22(6):577–584. https://doi.org/10.1002/nbm.1369
Alberich R, Castro JA, Llabrés M, Palmer-Rodríguez P. Metabolomics analysis: Finding out metabolic building blocks. PLoS One. 2017;12(5):e0177031. https://doi.org/10.1371/journal.pone.0177031
Arulkumaran N, Unwin RJ, Tam FW. A potential therapeutic role for P2X7 receptor (P2X7R) antagonists in the treatment of inflammatory diseases. Expert Opin Investig Drugs. 2011;20(7):897–915. https://doi.org/10.1517/13543784.2011.578068
Yu J, Chen Y, Li M, Gao Q, Peng Y, Gong Q, et al. Paeoniflorin down-regulates ATP-induced inflammatory cytokine production and P2X7R expression on peripheral blood mononuclear cells from patients with primary Sjögren’s syndrome. Int Immunopharmacol. 2015;28(1):115–120. https://doi.org/10.1016/j.intimp.2015.05.023
Lester S, Stokes L, Skarratt KK, Gu BJ, Sivils KL, Lessard CJ, et al. Epistasis with HLA DR3 implicates the P2X7 receptor in the pathogenesis of primary Sjögren’s syndrome. Arthritis Res Ther. 2013;15:R71. https://doi.org/10.1186/ar4248
Kim C, Cha YN. Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects. Amino Acids. 2014 Jan;46(1):89-100. doi: 10.1007/s00726-013-1545-6. Epub 2013 Aug 11. PMID: 23933994.
Guerrero-Gómez D, Mora-Lorca JA, Sáenz-Narciso B, Naranjo-Galindo FJ, Muñoz-Lobato F, Parrado-Fernández C, et al. Loss of glutathione redox homeostasis impairs proteostasis by inhibiting autophagy-dependent protein degradation. Cell Death Differ. 2019;26:1545–1565. https://doi.org/10.1038/s41418-018-0270-9