{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:48:29Z","timestamp":1793155709525,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare","award":["HR16C0001"],"award-info":[{"award-number":["HR16C0001"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1A2B5B01001767"],"award-info":[{"award-number":["NRF-2021R1A2B5B01001767"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sphingolipids are essential for cellular structure and signaling, and recent evidence implicates them in chronic inflammation. We hypothesized that altered sphingolipid metabolism contributes to the disease activity of systemic lupus erythematosus (SLE). Serum sphingolipids were quantified by liquid chromatography\u2013tandem mass spectrometry in 38 female SLE patients (11 with lupus nephritis [LN], 27 without LN) and 30 age-matched healthy controls (HCs). Serum ceramide (Cer)16\/sphingosine-1-phosphate (S1P) ratios were elevated in SLE compared to HCs (0.33 [0.26\u20130.38] vs. 0.25 [0.21\u20130.3], p = 0.019). Notably, Cer16\/S1P levels were significantly higher in the LN group (0.33 [0.26\u20130.38]) than in non-LN SLE (0.27 [0.2\u20130.34], p = 0.027). ROC analysis showed good diagnostic potential for LN (AUC = 0.739). Cer16\/S1P correlated positively with disease activity markers, including erythrocyte sedimentation rate (r = 0.519, p = 0.001), SLE Disease Activity Index 2000 (SLEDAI-2k) score (r = 0.547, p &lt; 0.001), anti-double stranded DNA antibody levels (r = 0.359, p = 0.027), and the Systemic Lupus International Collaborating Clinics\/American College of Rheumatology Damage Index (r = 0.327, p = 0.045). The serum Cer16\/S1P ratio may serve as a surrogate marker of disease activity in patients with LN.<\/jats:p>","DOI":"10.3390\/ijms262411957","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T15:43:43Z","timestamp":1765467823000},"page":"11957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploratory Pilot Study on the Serum Ceramide (16:0) to Sphingosine-1-Phosphate Ratio as a Potential Indicator of Lupus Nephritis and Disease Activity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-0884","authenticated-orcid":false,"given":"Ji-Won","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-Ro, Yeongtong-Gu, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Translational Research Laboratory for Inflammatory Disease, Clinical Trial Center, Ajou University Medical Center, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-4439","authenticated-orcid":false,"given":"Wook-Young","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-Ro, Yeongtong-Gu, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-0795","authenticated-orcid":false,"given":"Ju-Yang","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-Ro, Yeongtong-Gu, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-3367","authenticated-orcid":false,"given":"Hyoun-Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-Ro, Yeongtong-Gu, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-393X","authenticated-orcid":false,"given":"Chang-Hee","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-Ro, Yeongtong-Gu, Suwon 16499, Republic of Korea"},{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1001\/jama.2024.2315","article-title":"Systemic Lupus Erythematosus: A Review","volume":"331","author":"Siegel","year":"2024","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1136\/ard-2022-223741","article-title":"Pathogenesis of Systemic Lupus Erythematosus: Risks, Mechanisms and Therapeutic Targets","volume":"82","author":"Crow","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature13475","article-title":"Sphingolipid Metabolites in Inflammatory Disease","volume":"510","author":"Maceyka","year":"2014","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cmet.2021.06.006","article-title":"Sphingolipids in Metabolic Disease: The Good, the Bad, and the Unknown","volume":"33","author":"Green","year":"2021","journal-title":"Cell Metab."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Castillo, R.I., Rojo, L.E., Henriquez-Henriquez, M., Silva, H., Maturana, A., Villar, M.J., Fuentes, M., and Gaspar, P.A. (2016). From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome through Sphingolipids Metabolism. Front. Neurosci., 10.","DOI":"10.3389\/fnins.2016.00488"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/s12276-023-01018-9","article-title":"Functional Roles of Sphingolipids in Immunity and Their Implication in Disease","volume":"55","author":"Lee","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Harden, O.C., and Hammad, S.M. (2020). Sphingolipids and Diagnosis, Prognosis, and Organ Damage in Systemic Lupus Erythematosus. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.586737"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1681\/ASN.2014050508","article-title":"Renal Glycosphingolipid Metabolism Is Dysfunctional in Lupus Nephritis","volume":"26","author":"Nowling","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1177\/0961203316686707","article-title":"Dysregulations in Circulating Sphingolipids Associate with Disease Activity Indices in Female Patients with Systemic Lupus Erythematosus: A Cross-Sectional Study","volume":"26","author":"Checa","year":"2017","journal-title":"Lupus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.3945\/ajcn.115.111989","article-title":"Metabolic Profiles of Male Meat Eaters, Fish Eaters, Vegetarians, and Vegans from the EPIC-Oxford Cohort","volume":"102","author":"Schmidt","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hicks, A.A., Pramstaller, P.P., Johansson, A., Vitart, V., Rudan, I., Ugocsai, P., Aulchenko, Y., Franklin, C.S., Liebisch, G., and Erdmann, J. (2009). Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000672"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1038\/s44320-025-00146-w","article-title":"Deciphering Cross-Cohort Metabolic Signatures of Immune Responses and Their Implications for Disease Pathogenesis","volume":"21","author":"Fu","year":"2025","journal-title":"Mol. Syst. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11306-025-02292-6","article-title":"Mapping Current Research Status and Emerging Frontiers of Lipidomics: A Comprehensive Data-Mining-Based Study","volume":"21","author":"Li","year":"2025","journal-title":"Metabolomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/rheumatology\/keg212","article-title":"Cardiovascular Risk in Systemic Lupus Erythematosus\u2014Evidence of Increased Oxidative Stress and Dyslipidaemia","volume":"42","author":"Nuttall","year":"2003","journal-title":"Rheumatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1002\/art.40174","article-title":"Race\/Ethnicity and Cardiovascular Events Among Patients with Systemic Lupus Erythematosus","volume":"69","author":"Barbhaiya","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Alexandropoulou, I., Grammatikopoulou, M.G., Gkouskou, K.K., Pritsa, A.A., Vassilakou, T., Rigopoulou, E., Lindqvist, H.M., and Bogdanos, D.P. (2023). Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment. Nutrients, 15.","DOI":"10.3390\/nu15010229"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.2279","article-title":"The NLRP3 Inflammasome Instigates Obesity-Induced Inflammation and Insulin Resistance","volume":"17","author":"Vandanmagsar","year":"2011","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0891-5849(01)00655-4","article-title":"Ceramide in Apoptosis Signaling: Relationship with Oxidative Stress","volume":"31","author":"Salvayre","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mallela, S.K., Merscher, S., and Fornoni, A. (2022). Implications of Sphingolipid Metabolites in Kidney Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084244"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106348","DOI":"10.1016\/j.prostaglandins.2019.106348","article-title":"Blood Ceramides as Novel Markers for Renal Impairment in Systemic Lupus Erythematosus","volume":"144","author":"Patyna","year":"2019","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.advms.2023.10.004","article-title":"Ceramides and Their Roles in Programmed Cell Death","volume":"68","author":"Mezencev","year":"2023","journal-title":"Adv. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lu, L., Hu, C., Zhao, Y., He, L., Zhou, J., Li, H., Du, Y., Wang, Y., Wen, C., and Han, X. (2018). Shotgun Lipidomics Revealed Altered Profiles of Serum Lipids in Systemic Lupus Erythematosus Closely Associated with Disease Activity. Biomolecules, 8.","DOI":"10.3390\/biom8040105"},{"key":"ref_23","first-page":"857","article-title":"Lipidomic and Metabolomic Profiling Reveals Novel Candidate Biomarkers in Active Systemic Lupus Erythematosus","volume":"12","author":"Li","year":"2019","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hammad, S.M., Harden, O.C., Wilson, D.A., Twal, W.O., Nietert, P.J., and Oates, J.C. (2021). Plasma Sphingolipid Profile Associated with Subclinical Atherosclerosis and Clinical Disease Markers of Systemic Lupus Erythematosus: Potential Predictive Value. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.694318"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s12276-022-00725-z","article-title":"Lipidome Profile Predictive of Disease Evolution and Activity in Rheumatoid Arthritis","volume":"54","author":"Koh","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Huang, C.-C., Tseng, T.-T., Liu, S.-C., Lin, Y.-Y., Law, Y.-Y., Hy, S.-L., Wang, S.-W., Tsai, C.-H., and Tang, C.-H. (2021). S1P Increases VEGF Production in Osteoblasts and Facilitates Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-16-5p Expression via the c-Src\/FAK Signaling Pathway in Rheumatoid Arthritis. Cells, 10.","DOI":"10.3390\/cells10082168"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fineide, F., Chen, X., Bjellaas, T., Vitelli, V., Utheim, T.P., Jense, J.L., and Galtung, H.K. (2021). Characterization of Lipids in Saliva, Tears and Minor Salivary Glands of Sj\u00f6gren\u2019s Syndrome Patients Using an HPLC\/MS-Based Approach. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168997"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Geroldinger-Simi\u0107, M., B\u00f6gl, T., Himmelsbach, M., Sepp, N., and Buchberger, W. (2021). Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis. Diagnostics, 11.","DOI":"10.3390\/diagnostics11112116"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R142","DOI":"10.1186\/ar4604","article-title":"The Interaction between C5a and Sphingosine-1-Phosphate in Neutrophils for Antineutrophil Cytoplasmic Antibody-Mediated Activation","volume":"16","author":"Hao","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41586-024-07098-5","article-title":"IL-10 Constrains Sphingolipid Metabolism to Limit Inflammation","volume":"627","author":"York","year":"2024","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.4049\/jimmunol.1103109","article-title":"Ceramide Synthase 6 Plays a Critical Role in the Development of Experimental Autoimmune Encephalomyelitis","volume":"188","author":"Schiffmann","year":"2012","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104565","DOI":"10.1016\/j.msard.2023.104565","article-title":"Ceramide Is Implicated in Humoral Peripheral and Intrathecal Autoimmune Response in MS Patients","volume":"71","author":"Podbielska","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1016\/j.jacc.2020.02.062","article-title":"Circulating Ceramide 16:0 in Heart Failure with Preserved Ejection Fraction","volume":"75","author":"Javaheri","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"436","DOI":"10.3945\/ajcn.113.070557","article-title":"Dietary Intake of Palmitate and Oleate Has Broad Impact on Systemic and Tissue Lipid Profiles in Humans","volume":"99","author":"Kien","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_35","first-page":"10-1681","article-title":"CerS6 and C16 Ceramide in Early-Stage Diabetic Kidney Disease: Potential Role of Adenine in Podocytopathy: SA-PO0315","volume":"36","author":"Zhang","year":"2025","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"A53","DOI":"10.1136\/annrheumdis-2013-205124.121","article-title":"Screening of Sphingolipids in SLE\u2014Before and After Treatment","volume":"73","author":"Idborg","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1111\/j.1476-5381.2009.00281.x","article-title":"Sphingolipids in Inflammation: Pathological Implications and Potential Therapeutic Targets","volume":"158","author":"Nixon","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hammad, S.M., Hardin, J.R., Wilson, D.A., Twal, W.O., Nietert, P.J., and Oates, J.C. (2019). Race Disparity in Blood Sphingolipidomics Associated with Lupus Cardiovascular Comorbidity. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224496"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Espinoza, K.S., and Snider, A.J. (2024). Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer. Cancers, 16.","DOI":"10.3390\/cancers16040789"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/s41580-024-00742-y","article-title":"Regulation of Cellular and Systemic Sphingolipid Homeostasis","volume":"25","author":"Kuo","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kim, J.W., Baek, W.Y., Jung, J.Y., Kim, H.A., Lee, S.W., and Suh, C.H. (2024). Longitudinal Assessment of Urinary ALCAM, HPX, and PRDX6 in Korean Patients with Systemic Lupus Erythematosus: Implications for Disease Activity Monitoring and Treatment Response. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1369385"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kim, J.W., Jung, J.Y., Lee, S.W., Baek, W.Y., Kim, H.A., and Suh, C.H. (2022). S100A8 in Serum, Urine, and Saliva as a Potential Biomarker for Systemic Lupus Erythematosus. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.886209"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11957\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T05:25:40Z","timestamp":1765603540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":42,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411957"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411957","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]}}}