{"entity": "publication", "iuid": "8d14184492794542a7e1be543160a074", "timestamp": "2026-08-29T04:18:05.998Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8d14184492794542a7e1be543160a074.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8d14184492794542a7e1be543160a074"}}, "title": "Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression.", "authors": [{"family": "Ewing", "given": "Ewoud", "initials": "E"}, {"family": "Kular", "given": "Lara", "initials": "L"}, {"family": "Fernandes", "given": "Sunjay J", "initials": "SJ"}, {"family": "Karathanasis", "given": "Nestoras", "initials": "N"}, {"family": "Lagani", "given": "Vincenzo", "initials": "V"}, {"family": "Ruhrmann", "given": "Sabrina", "initials": "S"}, {"family": "Tsamardinos", "given": "Ioannis", "initials": "I"}, {"family": "Tegner", "given": "Jesper", "initials": "J"}, {"family": "Piehl", "given": "Fredrik", "initials": "F"}, {"family": "Gomez-Cabrero", "given": "David", "initials": "D"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}], "type": "journal article", "published": "2019-05-00", "journal": {"title": "EBioMedicine", "issn": "2352-3964", "volume": "43", "pages": "411-423", "issn-l": "2352-3964"}, "abstract": "Multiple Sclerosis (MS) is a chronic inflammatory disease and a leading cause of progressive neurological disability among young adults. DNA methylation, which intersects genes and environment to control cellular functions on a molecular level, may provide insights into MS pathogenesis.\n\nWe measured DNA methylation in CD4+ T cells (n = 31), CD8+ T cells (n = 28), CD14+ monocytes (n = 35) and CD19+ B cells (n = 27) from relapsing-remitting (RRMS), secondary progressive (SPMS) patients and healthy controls (HC) using Infinium HumanMethylation450 arrays. Monocyte (n = 25) and whole blood (n = 275) cohorts were used for validations.\n\nB cells from MS patients displayed most significant differentially methylated positions (DMPs), followed by monocytes, while only few DMPs were detected in T cells. We implemented a non-parametric combination framework (omicsNPC) to increase discovery power by combining evidence from all four cell types. Identified shared DMPs co-localized at MS risk loci and clustered into distinct groups. Functional exploration of changes discriminating RRMS and SPMS from HC implicated lymphocyte signaling, T cell activation and migration. SPMS-specific changes, on the other hand, implicated myeloid cell functions and metabolism. Interestingly, neuronal and neurodegenerative genes and pathways were also specifically enriched in the SPMS cluster.\n\nWe utilized a statistical framework (omicsNPC) that combines multiple layers of evidence to identify DNA methylation changes that provide new insights into MS pathogenesis in general, and disease progression, in particular. FUND: This work was supported by the Swedish Research Council, Stockholm County Council, AstraZeneca, European Research Council, Karolinska Institutet and Margaretha af Ugglas Foundation.", "doi": "10.1016/j.ebiom.2019.04.042", "pmid": "31053557", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6558224"}, {"db": "pii", "key": "S2352-3964(19)30281-6"}], "notes": [], "created": "2026-08-21T11:18:20.866Z", "modified": "2026-08-21T11:18:20.892Z"}