{"entity": "researcher", "timestamp": "2026-06-10T00:40:42.602Z", "family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "affiliations": ["Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, SE-171 76 Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8"}}, "publications": [{"entity": "publication", "iuid": "1e5708bc6c1c4c099e773f1d29e68641", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1e5708bc6c1c4c099e773f1d29e68641.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1e5708bc6c1c4c099e773f1d29e68641"}}, "title": "Anoctamin-2-specific T cells link Epstein-Barr virus to multiple sclerosis.", "authors": [{"family": "Thomas", "given": "Olivia G", "initials": "OG", "orcid": "0000-0002-2011-1344", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea07f812ffee4db893c6f98548563525.json"}}, {"family": "Rykaczewska", "given": "Urszula", "initials": "U"}, {"family": "Gale\u0161i\u0107", "given": "Marina", "initials": "M"}, {"family": "van der Burgt", "given": "Rianne T M", "initials": "RTM"}, {"family": "Hall\u00e9n", "given": "Nils", "initials": "N"}, {"family": "Ferro", "given": "Filippo", "initials": "F", "orcid": "0000-0002-6023-8227", "researcher": {"href": "https://publications.scilifelab.se/researcher/27810903638948feb4391fa537a7eda3.json"}}, {"family": "Bronge", "given": "Mattias", "initials": "M", "orcid": "0000-0002-1258-3982", "researcher": {"href": "https://publications.scilifelab.se/researcher/691b77352a57408896ef1fb486980ccd.json"}}, {"family": "Marti", "given": "Zoe", "initials": "Z"}, {"family": "Li", "given": "Yue", "initials": "Y"}, {"family": "Riqu\u00e9", "given": "Alexandra Hill", "initials": "AH"}, {"family": "Lin", "given": "Jianing", "initials": "J"}, {"family": "Krstic", "given": "Aleksa", "initials": "A"}, {"family": "Gromadzka", "given": "Alicja", "initials": "A"}, {"family": "Szonder", "given": "Andr\u00e1s Levente", "initials": "AL"}, {"family": "Sorini", "given": "Chiara", "initials": "C", "orcid": "0000-0002-6803-8377", "researcher": {"href": "https://publications.scilifelab.se/researcher/975173f37f144f06b236817e224de7f0.json"}}, {"family": "Reina-Campos", "given": "Mar\u00eda", "initials": "M"}, {"family": "Sun", "given": "Ting", "initials": "T", "orcid": "0000-0002-7104-7215", "researcher": {"href": "https://publications.scilifelab.se/researcher/521fca43267242fca06da0f5fc823e6a.json"}}, {"family": "Rubio Rodr\u00edguez-Kirby", "given": "Leslie A", "initials": "LA", "orcid": "0000-0003-4467-2661", "researcher": {"href": "https://publications.scilifelab.se/researcher/9790e215a63d40aa8fac497b537999f9.json"}}, {"family": "Dumral", "given": "\u00d6zge", "initials": "\u00d6", "orcid": "0000-0002-9980-2702", "researcher": {"href": "https://publications.scilifelab.se/researcher/8288edd47f70479e93e1fc441d486997.json"}}, {"family": "Berglund", "given": "Rasmus", "initials": "R"}, {"family": "Kakhki", "given": "Majid Pahlevan", "initials": "MP"}, {"family": "Adzemovic", "given": "Milena Z", "initials": "MZ"}, {"family": "Zeitelhofer", "given": "Manuel", "initials": "M"}, {"family": "Akpinar", "given": "Birce", "initials": "B"}, {"family": "Tengvall", "given": "Katarina", "initials": "K", "orcid": "0000-0003-0424-3571", "researcher": {"href": "https://publications.scilifelab.se/researcher/59b02aaaf03b4cd39150c3034888c81d.json"}}, {"family": "Nilsson", "given": "Ola B", "initials": "OB", "orcid": "0000-0002-7516-1760", "researcher": {"href": "https://publications.scilifelab.se/researcher/096ce3bf888b4ad395d53bb3c11f6946.json"}}, {"family": "Holmgren", "given": "Erik", "initials": "E", "orcid": "0000-0002-2656-1864", "researcher": {"href": "https://publications.scilifelab.se/researcher/6160949c45cf4daaab3991d051db5a16.json"}}, {"family": "Cucuzza", "given": "Chiara Starvaggi", "initials": "CS"}, {"family": "H\u00f6gelin", "given": "Klara Asplund", "initials": "KA"}, {"family": "Gafvelin", "given": "Guro", "initials": "G", "orcid": "0000-0003-1618-4011", "researcher": {"href": "https://publications.scilifelab.se/researcher/870294f4604744ccb212a3c299887ecc.json"}}, {"family": "Fink", "given": "Katharina", "initials": "K"}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}, {"family": "Needhamsen", "given": "Maria", "initials": "M"}, {"family": "Khademi", "given": "Mohsen", "initials": "M", "orcid": "0000-0003-0801-1444", "researcher": {"href": "https://publications.scilifelab.se/researcher/5446d6d754bc4c429d0e48ade419413c.json"}}, {"family": "Piehl", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-8329-5219", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee04062fbee34836a4fa3f4d2e8076cd.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications.scilifelab.se/researcher/52adbc739e274652bbf877facf4f0959.json"}}, {"family": "Alfredsson", "given": "Lars", "initials": "L", "orcid": "0000-0003-1688-6697", "researcher": {"href": "https://publications.scilifelab.se/researcher/6df230614a8a448e8607e03480169658.json"}}, {"family": "Lund", "given": "Harald", "initials": "H", "orcid": "0000-0001-8046-0805", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fe4902c355449e4812008d4ad7a37e0.json"}}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P", "orcid": "0000-0003-1446-1062", "researcher": {"href": "https://publications.scilifelab.se/researcher/91c3e953634140b8974186ac0d7eac85.json"}}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Martin", "given": "Roland", "initials": "R"}, {"family": "Jagodic", "given": "Maja", "initials": "M", "orcid": "0000-0003-0756-889X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b651ef39c6b0436992e2305f425eba72.json"}}, {"family": "Gr\u00f6nlund", "given": "Hans", "initials": "H", "orcid": "0000-0003-4882-7624", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e701613f60249b793f2def737168a05.json"}}, {"family": "Guerreiro-Cacais", "given": "Andr\u00e9 Ortlieb", "initials": "AO", "orcid": "0000-0002-4561-2823", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b824181455243b19f4aa145a4545870.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T"}], "type": "journal article", "published": "2026-01-22", "journal": {"title": "Cell", "issn": "1097-4172", "issn-l": "0092-8674", "volume": "189", "issue": "2", "pages": "585-602.e38"}, "abstract": "Epstein-Barr virus (EBV) infection constitutes a prerequisite for multiple sclerosis (MS) development, and cross-reactivity between EBV nuclear antigen 1 (EBNA1) and anoctamin-2 (ANO2) antibodies was previously demonstrated in persons with MS (pwMS). Here, we show that ANO2-specific CD4+ T cells are more frequent in pwMS. Immunization of SJL/J mice with ANO2 or EBNA1 led to cross-reactive CD4+ T cell and antibody responses. ANO2 pre-immunization led to exacerbated experimental autoimmune encephalomyelitis (EAE), an effect mediated by CD4+ T cells, as confirmed by adoptive transfer experiments. T cell clones with cross-reactivity to EBNA1 and ANO2 could be isolated from natalizumab-treated pwMS, and sequencing of EBNA1- and ANO2-specific T cell receptors (TCRs) revealed a significant repertoire overlap. We thus report the first mechanistic evidence that EBNA1 CD4+ T cells can target the MS autoantigen ANO2, thereby establishing a link between EBV infection and neuroinflammation.", "doi": "10.1016/j.cell.2025.12.032", "pmid": "41534529", "labels": {"Autoimmunity and Serology Profiling": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "S0092-8674(25)01481-3"}], "notes": [], "created": "2026-01-15T20:23:02.729Z", "modified": "2026-03-24T09:17:16.086Z"}, {"entity": "publication", "iuid": "f8ff8e625f5d45218a355407b7607936", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f8ff8e625f5d45218a355407b7607936.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f8ff8e625f5d45218a355407b7607936"}}, "title": "Co-exposure to PFAS and hydroxylated PCBs is associated with increased odds of multiple sclerosis", "authors": [{"family": "Vaivade", "given": "Aina", "initials": "A"}, {"family": "Sreenivasan", "given": "Akshai Parakkal", "initials": "AP", "orcid": "0000-0002-7293-6487", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b2f62a3bda9471d9227a6924b8adf7c.json"}}, {"family": "Erngren", "given": "Ida", "initials": "I", "orcid": "0000-0001-7867-9525", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8a16aaaf5194acba6b8649690a101d8.json"}}, {"family": "Freyhult", "given": "Eva", "initials": "E", "orcid": "0000-0003-0226-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/be110f11a53d4dcfa3bfd1657167895e.json"}}, {"family": "Emami Khoonsari", "given": "Payam", "initials": "P"}, {"family": "Siljebo", "given": "Jakob", "initials": "J"}, {"family": "Al-Grety", "given": "Asma", "initials": "A"}, {"family": "Carlsson", "given": "Henrik", "initials": "H", "orcid": "0000-0001-5558-6641", "researcher": {"href": "https://publications.scilifelab.se/researcher/de9581804a0b4b22991b34ebe89e9017.json"}}, {"family": "\u00c5kerfeldt", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Spjuth", "given": "Ola", "initials": "O", "orcid": "0000-0002-8083-2864", "researcher": {"href": "https://publications.scilifelab.se/researcher/605dbd52684d4e54ae4150a9933abe6e.json"}}, {"family": "Hedstr\u00f6m", "given": "Anna Karin", "initials": "AK", "orcid": "0000-0002-6612-4749", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4a1c4b315cd4a09b8f98a87b6cd2fba.json"}}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Alfredsson", "given": "Lars", "initials": "L", "orcid": "0000-0003-1688-6697", "researcher": {"href": "https://publications.scilifelab.se/researcher/6df230614a8a448e8607e03480169658.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Burman", "given": "Joachim", "initials": "J", "orcid": "0000-0002-7045-1806", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b9b82661abc49baaeac34bfcfc45321.json"}}, {"family": "Kultima", "given": "Kim", "initials": "K", "orcid": "0000-0002-0680-1410", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ae376585168459681f5e2cae0c75b96.json"}}], "type": "journal-article", "published": "2026-01-00", "journal": {"title": "Environment International", "issn": "0160-4120", "issn-l": "0160-4120", "volume": "207", "issue": null, "pages": "109993"}, "abstract": "Persistent organic pollutants often co-occur in human exposure environments, yet their combined effects on disease risk remain poorly understood. This study examined associations between serum concentrations of 14 per- and polyfluorinated substances (PFAS) and three hydroxylated polychlorinated biphenyls (OH-PCBs) and the onset of multiple sclerosis (MS), utilizing data from the Swedish population-based Epidemiological Investigation of Multiple Sclerosis (EIMS) cohort, comprising 907 MS cases and 907 matched controls. We employed single-substance logistic regression and quantile g-computation to evaluate cumulative and individual compound associations. We considered linear and non-linear risk patterns while adjusting for lifestyle factors and MS-associated HLA alleles. Our analysis revealed non-linear associations for several individual compounds, particularly perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid, 2,2',3,4',5,5',6-heptachloro-4-biphenylol (4-OH-CB187), and 2,2',4,4',5,5'-, Hexachloro-3-biphenylol (3-OH-CB153), with increased odds of MS. Interaction analyses further indicated that the association between PFOS and MS odds was modified by the presence of the HLA-B*44:02 allele, known for its protective effect on MS risk. Mixture modeling highlighted that combined exposures to PFAS and OH-PCBs significantly increased MS odds, even when associations for individual compounds were weak or absent. These findings emphasize the complexity of associations between environmental contaminants, lifestyle and genetic risk factors, and the odds of MS. They underscore the importance of addressing co-exposure in environmental health research and call for further studies to elucidate underlying biological mechanisms.", "doi": "10.1016/j.envint.2025.109993", "pmid": "41411973", "labels": {"Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0160-4120(25)00744-5"}], "notes": [], "created": "2026-02-10T09:53:14.232Z", "modified": "2026-03-24T09:16:23.730Z"}, {"entity": "publication", "iuid": "10591e3d44e348ae915ead7ea930d86d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/10591e3d44e348ae915ead7ea930d86d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/10591e3d44e348ae915ead7ea930d86d"}}, "title": "Depression Polygenicity and Disease Activity and Disability Worsening in Multiple Sclerosis.", "authors": [{"family": "Manouchehrinia", "given": "Ali", "initials": "A", "orcid": "0000-0003-4857-5762", "researcher": {"href": "https://publications.scilifelab.se/researcher/766e4d714e3042e4ae90d750ce82f7a7.json"}}, {"family": "Fitzgerald", "given": "Kathryn C", "initials": "KC", "orcid": "0000-0003-3137-0322", "researcher": {"href": "https://publications.scilifelab.se/researcher/40befe8eee6041638b4965633a08c8c6.json"}}, {"family": "Salter", "given": "Amber", "initials": "A", "orcid": "0000-0002-1088-110X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e42f735de154b4e8bc37333f48fda14.json"}}, {"family": "Marrie", "given": "Ruth Ann", "initials": "RA"}, {"family": "Alfredsson", "given": "Lars", "initials": "L"}, {"family": "Bernstein", "given": "Charles N", "initials": "CN"}, {"family": "Bolton", "given": "James M", "initials": "JM"}, {"family": "Cutter", "given": "Gary", "initials": "G"}, {"family": "Fisk", "given": "John D", "initials": "JD"}, {"family": "Graff", "given": "Lesley A", "initials": "LA"}, {"family": "Hitchon", "given": "Carol A", "initials": "CA"}, {"family": "Hillert", "given": "Jan", "initials": "J"}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Lu", "given": "Yi", "initials": "Y"}, {"family": "Lublin", "given": "Fred D", "initials": "FD"}, {"family": "McKay", "given": "Kyla", "initials": "K", "orcid": "0000-0002-9081-1522", "researcher": {"href": "https://publications.scilifelab.se/researcher/83a3879af6e44ba08514eccba217cfa9.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Patten", "given": "Scott", "initials": "S"}, {"family": "Patki", "given": "Amit", "initials": "A"}, {"family": "Riel", "given": "Hayley", "initials": "H"}, {"family": "Shchetynsky", "given": "Klementy", "initials": "K"}, {"family": "Stridh", "given": "Pernilla", "initials": "P"}, {"family": "Tiwari", "given": "Hemant K", "initials": "HK"}, {"family": "Wolinsky", "given": "Jerry S", "initials": "JS", "orcid": "0000-0002-8197-2762", "researcher": {"href": "https://publications.scilifelab.se/researcher/728aee2d34af46ebb8a8f7d831f3209b.json"}}, {"family": "Kowalec", "given": "Kaarina", "initials": "K", "orcid": "0000-0003-3928-9879", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf9da956e23e4a63a823d9bad0c1d21c.json"}}], "type": "journal article", "published": "2025-11-00", "journal": {"title": "Ann Neurol", "issn": "1531-8249", "volume": "98", "issue": "5", "pages": "1057-1069", "issn-l": null}, "abstract": "A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.\n\nIn this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and tested its association with annualized relapse rate and worsening disability. In the US cohort, we additionally explored the time to relapse, number of enhancing lesions, and confirmed Expanded Disability Status Scale (EDSS) worsening during the study period.\n\nWe included 3,420 relapsing-onset PwMS of European genetic ancestry with a median follow-up of 3 to 5 years. Meta-analyses revealed for each 1-standard deviation increase in the depression PGS, the relapse rate increased (incidence rate ratio: 1.23, 95% confidence interval [CI] = 1.01-1.50). In the US cohort, higher depression PGS was associated with protocol-defined relapses (hazard ratio [HR] = 1.58, 95% CI = 1.03-2.43), and time to confirmed EDSS worsening (HR = 1.51, 95% CI = 1.03-2.22) with this effect largely direct.\n\nMeta-analyses showed a higher depression genetic burden was associated with increased MS disease activity. In the US clinical trial cohort only, we found a significant association between higher depression PGS and time to relapse and confirmed EDSS worsening. These findings may provide insights into MS disease activity and disability worsening. ANN NEUROL 2025;98:1057-1069.", "doi": "10.1002/ana.70020", "pmid": "40772555", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12577672"}], "notes": [], "created": "2025-11-28T10:39:49.074Z", "modified": "2025-11-28T10:39:49.506Z"}, {"entity": "publication", "iuid": "fcaf83e14171434292e517ec5c5af2a8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fcaf83e14171434292e517ec5c5af2a8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fcaf83e14171434292e517ec5c5af2a8"}}, "title": "Associations of PFAS and OH-PCBs with risk of multiple sclerosis onset and disability worsening.", "authors": [{"family": "Vaivade", "given": "Aina", "initials": "A"}, {"family": "Erngren", "given": "Ida", "initials": "I", "orcid": "0000-0001-7867-9525", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8a16aaaf5194acba6b8649690a101d8.json"}}, {"family": "Carlsson", "given": "Henrik", "initials": "H", "orcid": "0000-0001-5558-6641", "researcher": {"href": "https://publications.scilifelab.se/researcher/de9581804a0b4b22991b34ebe89e9017.json"}}, {"family": "Freyhult", "given": "Eva", "initials": "E", "orcid": "0000-0003-0226-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/be110f11a53d4dcfa3bfd1657167895e.json"}}, {"family": "Emami Khoonsari", "given": "Payam", "initials": "P"}, {"family": "Noui", "given": "Yassine", "initials": "Y", "orcid": "0000-0002-0513-7546", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e4b7066daf4084b24fdbbac41e3c9e.json"}}, {"family": "Al-Grety", "given": "Asma", "initials": "A"}, {"family": "\u00c5kerfeldt", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Spjuth", "given": "Ola", "initials": "O", "orcid": "0000-0002-8083-2864", "researcher": {"href": "https://publications.scilifelab.se/researcher/605dbd52684d4e54ae4150a9933abe6e.json"}}, {"family": "Gallo", "given": "Valentina", "initials": "V"}, {"family": "Larsson", "given": "Anders Olof", "initials": "AO"}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Hedstr\u00f6m", "given": "Anna Karin", "initials": "AK", "orcid": "0000-0002-6612-4749", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4a1c4b315cd4a09b8f98a87b6cd2fba.json"}}, {"family": "Alfredsson", "given": "Lars", "initials": "L", "orcid": "0000-0003-1688-6697", "researcher": {"href": "https://publications.scilifelab.se/researcher/6df230614a8a448e8607e03480169658.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Burman", "given": "Joachim", "initials": "J", "orcid": "0000-0002-7045-1806", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b9b82661abc49baaeac34bfcfc45321.json"}}, {"family": "Kultima", "given": "Kim", "initials": "K", "orcid": "0000-0002-0680-1410", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ae376585168459681f5e2cae0c75b96.json"}}], "type": "journal article", "published": "2025-02-27", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "2014", "issn-l": "2041-1723"}, "abstract": "Exposure to per- and polyfluorinated substances (PFAS) and hydroxylated polychlorinated biphenyls (OH-PCBs) is associated with adverse human health effects, including immunosuppression. It is unknown if these substances can affect the course of autoimmune diseases. This study was based on 907 individuals with multiple sclerosis (MS) and 907 matched controls, where the MS cases were followed longitudinally using the Swedish MS register. We demonstrate sex- and disease-specific differences in serum PFAS concentrations between individuals with MS and controls. Moreover, two OH-PCBs (4-OH-CB187 and 3-OH-CB153) are associated with an increased risk of developing multiple sclerosis, regardless of sex and immigration status. With a clinical follow-up time of up to 18 years, an increase in serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA) decreases the risk of confirmed disability worsening in both sexes, as well as perfluoroheptanesulfonic acid (PFHpS) and perfluorononanoic acid (PFNA), only in males with MS. These results show previously unknown associations between OH-PCBs and the risk of developing MS, as well as the inverse associations between PFAS exposure and the risk of disability worsening in MS.", "doi": "10.1038/s41467-025-57172-3", "pmid": "40016224", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-025-57172-3"}], "notes": [], "created": "2025-03-01T11:13:17.025Z", "modified": "2025-03-24T08:20:33.179Z"}, {"entity": "publication", "iuid": "c1686601bc6b4c808ba31fbb6c6d93d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1686601bc6b4c808ba31fbb6c6d93d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1686601bc6b4c808ba31fbb6c6d93d3"}}, "title": "A genetic-epigenetic interplay at 1q21.1 locus underlies CHD1L-mediated vulnerability to primary progressive multiple sclerosis.", "authors": [{"family": "Pahlevan Kakhki", "given": "Majid", "initials": "M", "orcid": "0000-0002-5407-3147", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f376c85cfbe4711ae41d9ee5ade8f09.json"}}, {"family": "Giordano", "given": "Antonino", "initials": "A"}, {"family": "Starvaggi Cucuzza", "given": "Chiara", "initials": "C", "orcid": "0000-0002-9088-7658", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ead2e8f98754d1586891eda5adb9e1a.json"}}, {"family": "Venkata S Badam", "given": "Tejaswi", "initials": "T"}, {"family": "Samudyata", "given": "Samudyata", "initials": "S"}, {"family": "Lem\u00e9e", "given": "Marianne Victoria", "initials": "MV", "orcid": "0000-0002-4897-0722", "researcher": {"href": "https://publications.scilifelab.se/researcher/361e3a91dc5245e587309759769414c8.json"}}, {"family": "Stridh", "given": "Pernilla", "initials": "P", "orcid": "0000-0003-4855-0039", "researcher": {"href": "https://publications.scilifelab.se/researcher/613e86be4685423093de57bb83be261b.json"}}, {"family": "Gkogka", "given": "Asimenia", "initials": "A"}, {"family": "Shchetynsky", "given": "Klementy", "initials": "K"}, {"family": "Harroud", "given": "Adil", "initials": "A", "orcid": "0000-0003-2616-7274", "researcher": {"href": "https://publications.scilifelab.se/researcher/91a769f610fb430e89258c1c30cbd23b.json"}}, {"family": "Gyllenberg", "given": "Alexandra", "initials": "A"}, {"family": "Liu", "given": "Yun", "initials": "Y"}, {"family": "Boddul", "given": "Sanjaykumar", "initials": "S"}, {"family": "James", "given": "Tojo", "initials": "T"}, {"family": "Sorosina", "given": "Melissa", "initials": "M"}, {"family": "Filippi", "given": "Massimo", "initials": "M", "orcid": "0000-0002-5485-0479", "researcher": {"href": "https://publications.scilifelab.se/researcher/8878f32c07334124b8e3bce42c94c076.json"}}, {"family": "Esposito", "given": "Federica", "initials": "F"}, {"family": "Wermeling", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-9633-677X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a34df8186ba24df3b14fe9743cf546b4.json"}}, {"family": "Gustafsson", "given": "Mika", "initials": "M", "orcid": "0000-0002-0048-4063", "researcher": {"href": "https://publications.scilifelab.se/researcher/466661ecb9274ecc8f1a832b95ef19b2.json"}}, {"family": "Casaccia", "given": "Patrizia", "initials": "P", "orcid": "0000-0002-4785-9264", "researcher": {"href": "https://publications.scilifelab.se/researcher/e62a7dde40bd454e9072ff43fff8a2ea.json"}}, {"family": "Hillert", "given": "Jan", "initials": "J"}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Sellgren", "given": "Carl M", "initials": "CM", "orcid": "0000-0001-9103-2785", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c0740ddfd6d4c98988b2a19096a9814.json"}}, {"family": "Golzio", "given": "Christelle", "initials": "C"}, {"family": "Kular", "given": "Lara", "initials": "L", "orcid": "0000-0002-2907-6071", "researcher": {"href": "https://publications.scilifelab.se/researcher/09563004a20543dc934dd4d3b1ceebd7.json"}}, {"family": "Jagodic", "given": "Maja", "initials": "M", "orcid": "0000-0003-0756-889X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b651ef39c6b0436992e2305f425eba72.json"}}], "type": "journal article", "published": "2024-07-30", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "6419", "issn-l": "2041-1723"}, "abstract": "Multiple Sclerosis (MS) is a heterogeneous inflammatory and neurodegenerative disease with an unpredictable course towards progressive disability. Treating progressive MS is challenging due to limited insights into the underlying mechanisms. We examined the molecular changes associated with primary progressive MS (PPMS) using a cross-tissue (blood and post-mortem brain) and multilayered data (genetic, epigenetic, transcriptomic) from independent cohorts. In PPMS, we found hypermethylation of the 1q21.1 locus, controlled by PPMS-specific genetic variations and influencing the expression of proximal genes (CHD1L, PRKAB2) in the brain. Evidence from reporter assay and CRISPR/dCas9 experiments supports a causal link between methylation and expression and correlation network analysis further implicates these genes in PPMS brain processes. Knock-down of CHD1L in human iPSC-derived neurons and knock-out of chd1l in zebrafish led to developmental and functional deficits of neurons. Thus, several lines of evidence suggest a distinct genetic-epigenetic-transcriptional interplay in the 1q21.1 locus potentially contributing to PPMS pathogenesis.", "doi": "10.1038/s41467-024-50794-z", "pmid": "39079955", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11289459"}, {"db": "pii", "key": "10.1038/s41467-024-50794-z"}], "notes": [], "created": "2024-08-15T12:14:24.965Z", "modified": "2024-11-25T10:17:37.116Z"}, {"entity": "publication", "iuid": "df5638c2c3d442cd861fa36a108950d6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/df5638c2c3d442cd861fa36a108950d6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/df5638c2c3d442cd861fa36a108950d6"}}, "title": "Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis.", "authors": [{"family": "\u00c5kesson", "given": "Julia", "initials": "J", "orcid": "0000-0002-9276-0546", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba1adc3a1e614b87808e3b1b5d4d9cb1.json"}}, {"family": "Hojjati", "given": "Sara", "initials": "S"}, {"family": "Hellberg", "given": "Sandra", "initials": "S"}, {"family": "Raffetseder", "given": "Johanna", "initials": "J", "orcid": "0000-0001-8871-2560", "researcher": {"href": "https://publications.scilifelab.se/researcher/604da06820f542ef84b97cf0e4641e2c.json"}}, {"family": "Khademi", "given": "Mohsen", "initials": "M", "orcid": "0000-0003-0801-1444", "researcher": {"href": "https://publications.scilifelab.se/researcher/5446d6d754bc4c429d0e48ade419413c.json"}}, {"family": "Rynkowski", "given": "Robert", "initials": "R"}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Altafini", "given": "Claudio", "initials": "C", "orcid": "0000-0003-4142-6502", "researcher": {"href": "https://publications.scilifelab.se/researcher/397523f1994046fdb4c462d5127e4c1d.json"}}, {"family": "Lubovac-Pilav", "given": "Zelmina", "initials": "Z", "orcid": "0000-0001-6427-0315", "researcher": {"href": "https://publications.scilifelab.se/researcher/af98c65fa2964875bd6d46f9c2488e6b.json"}}, {"family": "Mellerg\u00e5rd", "given": "Johan", "initials": "J", "orcid": "0000-0003-0120-3734", "researcher": {"href": "https://publications.scilifelab.se/researcher/f471bdcfc7fc4c2fb282484ac7e148bd.json"}}, {"family": "Jenmalm", "given": "Maria C", "initials": "MC", "orcid": "0000-0002-2117-5366", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf1f485192744e0c95ccecdb5471b577.json"}}, {"family": "Piehl", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-8329-5219", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee04062fbee34836a4fa3f4d2e8076cd.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Ernerudh", "given": "Jan", "initials": "J", "orcid": "0000-0001-9456-2044", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc016a1ad2b14e91b97b65d5aaae7f59.json"}}, {"family": "Gustafsson", "given": "Mika", "initials": "M", "orcid": "0000-0002-0048-4063", "researcher": {"href": "https://publications.scilifelab.se/researcher/466661ecb9274ecc8f1a832b95ef19b2.json"}}], "type": "journal article", "published": "2023-10-30", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "6903", "issn-l": "2041-1723"}, "abstract": "Sensitive and reliable protein biomarkers are needed to predict disease trajectory and personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) to quantify 1463 proteins in cerebrospinal fluid (CSF) and plasma from 143 people with early-stage MS and 43 healthy controls. With longitudinally followed discovery and replication cohorts, we identify CSF proteins that consistently predicted both short- and long-term disease progression. Lower levels of neurofilament light chain (NfL) in CSF is superior in predicting the absence of disease activity two years after sampling (replication AUC = 0.77) compared to all other tested proteins. Importantly, we also identify a combination of 11 CSF proteins (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B and NfL) that predict the severity of disability worsening according to the normalized age-related MS severity score (replication AUC = 0.90). The identification of these proteins may help elucidate pathogenetic processes and might aid decisions on treatment strategies for persons with MS.", "doi": "10.1038/s41467-023-42682-9", "pmid": "37903821", "labels": {"NGI Proteomics": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10616092"}, {"db": "pii", "key": "10.1038/s41467-023-42682-9"}], "notes": [], "created": "2023-11-23T07:26:00.330Z", "modified": "2023-11-29T18:44:34.331Z"}, {"entity": "publication", "iuid": "c47a067012124fd3b1e0a4b3a87b6c30", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c47a067012124fd3b1e0a4b3a87b6c30.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c47a067012124fd3b1e0a4b3a87b6c30"}}, "title": "Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis.", "authors": [{"family": "Thomas", "given": "Olivia G", "initials": "OG", "orcid": "0000-0002-2011-1344", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea07f812ffee4db893c6f98548563525.json"}}, {"family": "Bronge", "given": "Mattias", "initials": "M", "orcid": "0000-0002-1258-3982", "researcher": {"href": "https://publications.scilifelab.se/researcher/691b77352a57408896ef1fb486980ccd.json"}}, {"family": "Tengvall", "given": "Katarina", "initials": "K", "orcid": "0000-0003-0424-3571", "researcher": {"href": "https://publications.scilifelab.se/researcher/59b02aaaf03b4cd39150c3034888c81d.json"}}, {"family": "Akpinar", "given": "Birce", "initials": "B"}, {"family": "Nilsson", "given": "Ola B", "initials": "OB"}, {"family": "Holmgren", "given": "Erik", "initials": "E", "orcid": "0000-0002-2656-1864", "researcher": {"href": "https://publications.scilifelab.se/researcher/6160949c45cf4daaab3991d051db5a16.json"}}, {"family": "Hessa", "given": "Tara", "initials": "T"}, {"family": "Gafvelin", "given": "Guro", "initials": "G", "orcid": "0000-0003-1618-4011", "researcher": {"href": "https://publications.scilifelab.se/researcher/870294f4604744ccb212a3c299887ecc.json"}}, {"family": "Khademi", "given": "Mohsen", "initials": "M", "orcid": "0000-0003-0801-1444", "researcher": {"href": "https://publications.scilifelab.se/researcher/5446d6d754bc4c429d0e48ade419413c.json"}}, {"family": "Alfredsson", "given": "Lars", "initials": "L", "orcid": "0000-0003-1688-6697", "researcher": {"href": "https://publications.scilifelab.se/researcher/6df230614a8a448e8607e03480169658.json"}}, {"family": "Martin", "given": "Roland", "initials": "R", "orcid": "0000-0002-0982-1329", "researcher": {"href": "https://publications.scilifelab.se/researcher/64b3f80280694b0399130e6eb26caf72.json"}}, {"family": "Guerreiro-Cacais", "given": "Andr\u00e9 Ortlieb", "initials": "AO", "orcid": "0000-0002-4561-2823", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b824181455243b19f4aa145a4545870.json"}}, {"family": "Gr\u00f6nlund", "given": "Hans", "initials": "H", "orcid": "0000-0003-4882-7624", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e701613f60249b793f2def737168a05.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T", "orcid": "0000-0002-2938-1877", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd9a20a941214f97a22f010df37cd8e1.json"}}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}], "type": "journal article", "published": "2023-05-19", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "9", "issue": "20", "pages": "eadg3032", "issn-l": "2375-2548"}, "abstract": "Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which and Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly increased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homologous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4+ T cell responses were detected in natalizumab-treated pwMS. This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, further demonstrating the role of EBV adaptive immune responses in MS development.", "doi": "10.1126/sciadv.adg3032", "pmid": "37196088", "labels": {"Autoimmunity and Serology Profiling": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10191428"}], "notes": [], "created": "2023-06-25T20:13:34.600Z", "modified": "2023-06-25T20:13:34.874Z"}, {"entity": "publication", "iuid": "387be3d37549490b96f97b6b0818f875", "links": {"self": {"href": "https://publications.scilifelab.se/publication/387be3d37549490b96f97b6b0818f875.json"}, "display": {"href": "https://publications.scilifelab.se/publication/387be3d37549490b96f97b6b0818f875"}}, "title": "Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis.", "authors": [{"family": "Bronge", "given": "Mattias", "initials": "M", "orcid": "0000-0002-1258-3982", "researcher": {"href": "https://publications.scilifelab.se/researcher/691b77352a57408896ef1fb486980ccd.json"}}, {"family": "H\u00f6gelin", "given": "Klara Asplund", "initials": "KA"}, {"family": "Thomas", "given": "Olivia G", "initials": "OG", "orcid": "0000-0002-2011-1344", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea07f812ffee4db893c6f98548563525.json"}}, {"family": "Ruhrmann", "given": "Sabrina", "initials": "S"}, {"family": "Carvalho-Queiroz", "given": "Claudia", "initials": "C"}, {"family": "Nilsson", "given": "Ola B", "initials": "OB"}, {"family": "Kaiser", "given": "Andreas", "initials": "A"}, {"family": "Zeitelhofer", "given": "Manuel", "initials": "M"}, {"family": "Holmgren", "given": "Erik", "initials": "E", "orcid": "0000-0002-2656-1864", "researcher": {"href": "https://publications.scilifelab.se/researcher/6160949c45cf4daaab3991d051db5a16.json"}}, {"family": "Linnerbauer", "given": "Mathias", "initials": "M", "orcid": "0000-0002-5528-5141", "researcher": {"href": "https://publications.scilifelab.se/researcher/27c1386bf72f4371acb131d333314da2.json"}}, {"family": "Adzemovic", "given": "Milena Z", "initials": "MZ"}, {"family": "Hellstr\u00f6m", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-0880-5375", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbf3f75938f0442a9b1ae5c98565f44a.json"}}, {"family": "Jelcic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-6187-7098", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b5547919d474434bddd217865f1fb8e.json"}}, {"family": "Liu", "given": "Hao", "initials": "H", "orcid": "0000-0001-6572-2870", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3f8f259e77d4e208a4c838de8a7c7de.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Hillert", "given": "Jan", "initials": "J", "orcid": "0000-0002-7386-6732", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb4f3ad8831d430e8327dd457d43834b.json"}}, {"family": "Brundin", "given": "Lou", "initials": "L", "orcid": "0000-0003-4408-7817", "researcher": {"href": "https://publications.scilifelab.se/researcher/9181d700c722427099d882b3b40eb91e.json"}}, {"family": "Fink", "given": "Katharina", "initials": "K"}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Tengvall", "given": "Katarina", "initials": "K", "orcid": "0000-0003-0424-3571", "researcher": {"href": "https://publications.scilifelab.se/researcher/59b02aaaf03b4cd39150c3034888c81d.json"}}, {"family": "Martin", "given": "Roland", "initials": "R"}, {"family": "Tegel", "given": "Hanna", "initials": "H", "orcid": "0000-0002-7067-9173", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3d733dbd7b84a6b88f7f5fcff7165f6.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications.scilifelab.se/researcher/52adbc739e274652bbf877facf4f0959.json"}}, {"family": "Al Nimer", "given": "Faiez", "initials": "F", "orcid": "0000-0003-0937-5995", "researcher": {"href": "https://publications.scilifelab.se/researcher/743a318b1c64432280e3999fb57c9a18.json"}}, {"family": "Guerreiro-Cacais", "given": "Andr\u00e9 Ortlieb", "initials": "AO", "orcid": "0000-0002-4561-2823", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b824181455243b19f4aa145a4545870.json"}}, {"family": "Khademi", "given": "Mohsen", "initials": "M", "orcid": "0000-0003-0801-1444", "researcher": {"href": "https://publications.scilifelab.se/researcher/5446d6d754bc4c429d0e48ade419413c.json"}}, {"family": "Gafvelin", "given": "Guro", "initials": "G", "orcid": "0000-0003-1618-4011", "researcher": {"href": "https://publications.scilifelab.se/researcher/870294f4604744ccb212a3c299887ecc.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T", "orcid": "0000-0002-2938-1877", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd9a20a941214f97a22f010df37cd8e1.json"}}, {"family": "Gr\u00f6nlund", "given": "Hans", "initials": "H", "orcid": "0000-0003-4882-7624", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e701613f60249b793f2def737168a05.json"}}], "type": "journal article", "published": "2022-04-29", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "8", "issue": "17", "pages": "eabn1823", "issn-l": "2375-2548"}, "abstract": "Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), in which pathological T cells, likely autoimmune, play a key role. Despite its central importance, the autoantigen repertoire remains largely uncharacterized. Using a novel in vitro antigen delivery method combined with the Human Protein Atlas library, we screened for T cell autoreactivity against 63 CNS-expressed proteins. We identified four previously unreported autoantigens in MS: fatty acid-binding protein 7, prokineticin-2, reticulon-3, and synaptosomal-associated protein 91, which were verified to induce interferon-\u03b3 responses in MS in two cohorts. Autoreactive profiles were heterogeneous, and reactivity to several autoantigens was MS-selective. Autoreactive T cells were predominantly CD4+ and human leukocyte antigen-DR restricted. Mouse immunization induced antigen-specific responses and CNS leukocyte infiltration. This represents one of the largest systematic efforts to date in the search for MS autoantigens, demonstrates the heterogeneity of autoreactive profiles, and highlights promising targets for future diagnostic tools and immunomodulatory therapies in MS.", "doi": "10.1126/sciadv.abn1823", "pmid": "35476434", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [], "notes": [], "created": "2022-04-28T11:23:43.022Z", "modified": "2022-04-28T11:23:43.509Z"}, {"entity": "publication", "iuid": "59e9eed77d884982800369f681f6e500", "links": {"self": {"href": "https://publications.scilifelab.se/publication/59e9eed77d884982800369f681f6e500.json"}, "display": {"href": "https://publications.scilifelab.se/publication/59e9eed77d884982800369f681f6e500"}}, "title": "Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology.", "authors": [{"family": "Zheleznyakova", "given": "Galina Yurevna", "initials": "GY"}, {"family": "Piket", "given": "Eliane", "initials": "E"}, {"family": "Needhamsen", "given": "Maria", "initials": "M"}, {"family": "Hagemann-Jensen", "given": "Michael", "initials": "M"}, {"family": "Ekman", "given": "Diana", "initials": "D"}, {"family": "Han", "given": "Yanan", "initials": "Y"}, {"family": "James", "given": "Tojo", "initials": "T"}, {"family": "Khademi", "given": "Mohsen", "initials": "M", "orcid": "0000-0003-0801-1444", "researcher": {"href": "https://publications.scilifelab.se/researcher/5446d6d754bc4c429d0e48ade419413c.json"}}, {"family": "Al Nimer", "given": "Faiez", "initials": "F", "orcid": "0000-0003-0937-5995", "researcher": {"href": "https://publications.scilifelab.se/researcher/743a318b1c64432280e3999fb57c9a18.json"}}, {"family": "Scicluna", "given": "Patrick", "initials": "P"}, {"family": "Huang", "given": "Jesse", "initials": "J"}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Faridani", "given": "Omid R", "initials": "OR"}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Piehl", "given": "Fredrik", "initials": "F"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}], "type": "journal article", "published": "2021-04-27", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "118", "issue": "17", "pages": "e2011574118", "issn-l": "0027-8424"}, "abstract": "Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system (CNS). Small non-coding RNAs (sncRNAs) and, in particular, microRNAs (miRNAs) have frequently been associated with MS. Here, we performed a comprehensive analysis of all classes of sncRNAs in matching samples of peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells, and cell-free CSF from relapsing-remitting (RRMS, n = 12 in relapse and n = 11 in remission) patients, secondary progressive (SPMS, n = 6) MS patients, and noninflammatory and inflammatory neurological disease controls (NINDC, n = 11; INDC, n = 5). We show widespread changes in miRNAs and sncRNA-derived fragments of small nuclear, nucleolar, and transfer RNAs. In CSF cells, 133 out of 133 and 115 out of 117 differentially expressed sncRNAs were increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65 out of 67 differentially expressed PBMC sncRNAs were decreased in RRMS compared to NINDC. The striking contrast between the periphery and CNS suggests that sncRNA-mediated mechanisms, including alternative splicing, RNA degradation, and mRNA translation, regulate the transcriptome of pathogenic cells primarily in the CNS target organ.", "doi": "10.1073/pnas.2011574118", "pmid": "33879606", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "2011574118"}, {"db": "pmc", "key": "PMC8092379"}], "notes": [], "created": "2021-04-26T11:53:05.985Z", "modified": "2024-01-16T13:48:39.971Z"}, {"entity": "publication", "iuid": "7a14c5167e074030981441eb5dcefaad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a14c5167e074030981441eb5dcefaad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a14c5167e074030981441eb5dcefaad"}}, "title": "Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling.", "authors": [{"family": "Lundtoft", "given": "Christian", "initials": "C", "orcid": "0000-0001-5872-4253", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a05532d3aad4e2dbe00a4724e8dddd8.json"}}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications.scilifelab.se/researcher/61a214ff2d494b568cb6da944e858acf.json"}}, {"family": "Imgenberg-Kreuz", "given": "Juliana", "initials": "J", "orcid": "0000-0002-7230-8990", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d4c2f630d484ee780c2c12aaabdb939.json"}}, {"family": "Carlsson-Alml\u00f6f", "given": "Jonas", "initials": "J", "orcid": "0000-0002-1211-9821", "researcher": {"href": "https://publications.scilifelab.se/researcher/046904cd12eb4764bd2dcadc876f65d7.json"}}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML", "orcid": "0000-0002-8454-1351", "researcher": {"href": "https://publications.scilifelab.se/researcher/d162e060954d420e825884f254886dcd.json"}}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Nordmark", "given": "Gunnel", "initials": "G", "orcid": "0000-0002-3829-7431", "researcher": {"href": "https://publications.scilifelab.se/researcher/188fda53498740dbb007441cc94bb1ad.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T", "orcid": "0000-0002-2938-1877", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd9a20a941214f97a22f010df37cd8e1.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}, {"family": "Hagberg", "given": "Niklas", "initials": "N", "orcid": "0000-0003-2064-2716", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d0998bb419c424083b0978ebdbe8629.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "16", "issue": "10", "pages": "e1009199", "issn-l": "1553-7390"}, "abstract": "Interferons (IFNs) are cytokines that are central to the host defence against viruses and other microorganisms. If not properly regulated, IFNs may contribute to the pathogenesis of inflammatory autoimmune, or infectious diseases. To identify genetic polymorphisms regulating the IFN system we performed an unbiased genome-wide protein-quantitative trait loci (pQTL) mapping of cell-type specific type I and type II IFN receptor levels and their responses in immune cells from 303 healthy individuals. Seven genome-wide significant (p < 5.0E-8) pQTLs were identified. Two independent SNPs that tagged the multiple sclerosis (MS)-protective HLA class I alleles A*02/A*68 and B*44, respectively, were associated with increased levels of IFNAR2 in B and T cells, with the most prominent effect in IgD-CD27+ memory B cells. The increased IFNAR2 levels in B cells were replicated in cells from an independent set of healthy individuals and in MS patients. Despite increased IFNAR2 levels, B and T cells carrying the MS-protective alleles displayed a reduced response to type I IFN stimulation. Expression and methylation-QTL analysis demonstrated increased mRNA expression of the pseudogene HLA-J in B cells carrying the MS-protective class I alleles, possibly driven via methylation-dependent transcriptional regulation. Together these data suggest that the MS-protective effects of HLA class I alleles are unrelated to their antigen-presenting function, and propose a previously unappreciated function of type I IFN signalling in B and T cells in MS immune-pathogenesis.", "doi": "10.1371/journal.pgen.1009199", "pmid": "33104735", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-20-01001"}, {"db": "pmc", "key": "PMC7644105"}], "notes": [], "created": "2020-11-05T14:07:48.822Z", "modified": "2024-01-16T13:48:41.667Z"}, {"entity": "publication", "iuid": "8aad6ceb7086447cb14545d9433c1791", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8aad6ceb7086447cb14545d9433c1791.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8aad6ceb7086447cb14545d9433c1791"}}, "title": "Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk.", "authors": [{"family": "Tengvall", "given": "Katarina", "initials": "K", "orcid": "0000-0003-0424-3571", "researcher": {"href": "https://publications.scilifelab.se/researcher/59b02aaaf03b4cd39150c3034888c81d.json"}}, {"family": "Huang", "given": "Jesse", "initials": "J"}, {"family": "Hellstr\u00f6m", "given": "Cecilia", "initials": "C"}, {"family": "Kammer", "given": "Patrick", "initials": "P"}, {"family": "Bistr\u00f6m", "given": "Martin", "initials": "M"}, {"family": "Ayoglu", "given": "Burcu", "initials": "B"}, {"family": "Lima Bomfim", "given": "Izaura", "initials": "I"}, {"family": "Stridh", "given": "Pernilla", "initials": "P"}, {"family": "Butt", "given": "Julia", "initials": "J"}, {"family": "Brenner", "given": "Nicole", "initials": "N"}, {"family": "Michel", "given": "Angelika", "initials": "A"}, {"family": "Lundberg", "given": "Karin", "initials": "K"}, {"family": "Padyukov", "given": "Leonid", "initials": "L"}, {"family": "Lundberg", "given": "Ingrid E", "initials": "IE"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E"}, {"family": "Ernberg", "given": "Ingemar", "initials": "I"}, {"family": "Olafsson", "given": "Sigurgeir", "initials": "S"}, {"family": "Dilthey", "given": "Alexander T", "initials": "AT"}, {"family": "Hillert", "given": "Jan", "initials": "J"}, {"family": "Alfredsson", "given": "Lars", "initials": "L"}, {"family": "Sundstr\u00f6m", "given": "Peter", "initials": "P"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Waterboer", "given": "Tim", "initials": "T"}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}], "type": "clinical trial", "published": "2019-08-20", "journal": {"volume": "116", "issn": "1091-6490", "issue": "34", "pages": "16955-16960", "title": "Proc. Natl. Acad. Sci. U.S.A.", "issn-l": "0027-8424"}, "abstract": "Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 \u00d7 10-36) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95%CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15:01 carriage, absence of HLA-A*02:01, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLA-DRB1*04:01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95%CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.", "doi": "10.1073/pnas.1902623116", "pmid": "31375628", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "1902623116"}, {"db": "pmc", "key": "PMC6708327"}], "notes": [], "created": "2019-11-06T15:11:35.887Z", "modified": "2021-07-06T15:13:37.900Z"}]}