{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:47:49Z","timestamp":1782280069539,"version":"3.54.5"},"posted":{"date-parts":[[2025,3,13]]},"group-title":"Systems Biology","reference-count":10,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Sarcoidosis is an idiopathic syndrome with striking disparities in clinical outcome. We have previously identified immune distinctions between sarcoidosis clinical cohorts that either resolve or progress. A significantly higher percentage of Programmed Death 1 (PD-1)+Th17 cells was present in sarcoidosis and IPF subjects experiencing disease progression. Metabolites, or bioactive compounds, have been shown to interact with immune cells, such as Th17 cells by regulating cellular processes such as proliferation, signaling and differentiation. Metabolomic analysis was conducted on two subject cohorts: Sarcoidosis (n=19) and healthy controls (n=23). Sarcoidosis subjects were further subdivided by clinical outcome and prior to therapeutic initiation: disease progression or clinical resolution. Metabolites are considered significant if they had a fold change greater than two and a p-value is &lt;0.05 in pairwise 2-sample t-tests. Multiple group comparison was performed using ANOVA and Tukey\u2019s honestly significance difference post hoc tests to identify statistically different pairwise differences. Progressors exhibit significantly elevated serum levels of trimethylamine N-oxide (TMAO) and taurine, with reduced glycerate, alanine, and proline concentrations (Figure 1A-C). TMAO is elevated in sarcoidosis progressors relative to resolvers. Taurine levels are also significantly elevated in progressors, comparing to resolvers. The significant reductions in glycerate, alanine, and proline in progressors compared to resolvers, along with elevated TMAO, point to disruptions in core metabolic pathways, including glycolysis, pyruvate metabolism, and collagen synthesis, that underlie bioenergetic dysfunction, altered amino acid utilization, and impaired tissue repair.<\/jats:p>","DOI":"10.1101\/2025.03.10.642370","type":"posted-content","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T23:40:21Z","timestamp":1741909221000},"source":"Crossref","is-referenced-by-count":1,"title":["Sarcoidosis resolvers and progressors demonstrate distinct systemic metabolomic profiles"],"prefix":"10.64898","author":[{"given":"Bing","family":"Ma","sequence":"first","affiliation":[{"name":"University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD, USA"},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lobelia","family":"Samavati","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, Michigan"},{"name":"Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3488-2393","authenticated-orcid":false,"given":"Wonder Puryear","family":"Drake","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041022362796000_2025.03.10.642370v1.1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202002-0251ST"},{"key":"2026041022362796000_2025.03.10.642370v1.2","doi-asserted-by":"crossref","unstructured":"Celada LJ , Kropski JA , Herazo-Maya JD , Luo W , Creecy A , Abad AT , Chioma OS , Lee G , Hassell NE , Shaginurova GI , Wang Y , Johnson JE , Kerrigan A , Mason WR , Baughman RP , Ayers GD , Bernard GR , Culver DA , Montgomery CG , Maher TM , Molyneaux PL , Noth I , Mutsaers SE , Prele CM , Peebles RS, Jr ., Newcomb DC , Kaminski N , Blackwell TS , Van Kaer L , Drake WP . PD-1 up-regulation on CD4(+) T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-beta1 production. Sci Transl Med 2018; 10.","DOI":"10.1126\/scitranslmed.aar8356"},{"key":"2026041022362796000_2025.03.10.642370v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-04357-x"},{"key":"2026041022362796000_2025.03.10.642370v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986"},{"key":"2026041022362796000_2025.03.10.642370v1.5","doi-asserted-by":"crossref","unstructured":"Geamanu A , Gupta SV , Bauerfeld C , Samavati L. Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis. Metabolomics 2016; 12.","DOI":"10.1007\/s11306-015-0932-2"},{"key":"2026041022362796000_2025.03.10.642370v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-023-02052-4"},{"key":"2026041022362796000_2025.03.10.642370v1.7","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-7-142"},{"key":"2026041022362796000_2025.03.10.642370v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3145"},{"key":"2026041022362796000_2025.03.10.642370v1.9","doi-asserted-by":"crossref","unstructured":"Gonzalez-Correa C , Moleon J , Minano S , Visitacion N , Robles-Vera I , Gomez-Guzman M , Jimenez R , Romero M , Duarte J. Trimethylamine N-Oxide Promotes Autoimmunity and a Loss of Vascular Function in Toll-like Receptor 7-Driven Lupus Mice. Antioxidants (Basel) 2021; 11.","DOI":"10.3390\/antiox11010084"},{"key":"2026041022362796000_2025.03.10.642370v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2008.10.007"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.10.642370","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:56:14Z","timestamp":1782276974000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.03.10.642370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,13]]},"references-count":10,"URL":"https:\/\/doi.org\/10.1101\/2025.03.10.642370","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1164\/rccm.202503-0772RL","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,3,13]]},"subtype":"preprint"}}