{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:04:48Z","timestamp":1790661888993,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011697","name":"R\u00e9gion Bretagne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011697","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Sj\u00f6gren's disease (SjD) is a chronic autoimmune condition marked by lymphocytic infiltration of exocrine glands and production of autoantibodies such as anti\u2010SSA\/Ro, anti\u2010SSB\/La, and rheumatoid factor. B lymphocytes play a central role in disease pathogenesis, driving autoantibody production and glandular damage, and contributing to lymphomagenesis. Despite promising therapies, no effective treatment is currently available, partly due to the biological and clinical heterogeneity of the disease. While interferon (IFN) signatures and B cell\u2013related markers are used for patient stratification, their integration remains unexplored. This study analyzed B cell transcriptional and metabolic profiles using bulk transcriptomic, clinical, and flow cytometry data from the PRECISESADS consortium, alongside public single\u2010cell RNA\u2010sequencing datasets. A B cell\u2013specific IFN\u2010\u03b1 signature was established to stratify patients into IFN\u2010positive and IFN\u2010negative groups. Both showed reduced oxidative phosphorylation (OXPHOS) and translation in B cell subsets, suggesting a shared early metabolic reprogramming state. IFN\u2010positive patients, however, displayed additional features, including enhanced glycolysis, amino acid and lipid metabolism, autophagy, and NF\u2010\u03baB signaling. They also showed an expansion of IFN\u2010activated\u2010na\u00efve (naive IFN), Transitional, and double\u2010negative (DN) B cells, particularly DN2 and DN2_CXCR3 subsets, which have been linked in the literature to autoreactivity and lymphoma development. The IFN\u2010signature in na\u00efve B cells and DN2 correlated with elevated anti\u2010SSA\/Ro and anti\u2010SSB\/La titers, while only na\u00efve B cells showed an association with increased histological focus scores. These findings support B cell\u2013specific IFN signature relevance in stratifying SjD patients and suggest new metabolic and transcriptional targets for disease monitoring and therapeutic development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/eji.70275","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:43:57Z","timestamp":1790574237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interferon\u2010\u03b1\u2013Driven Stratification of B Cells Reveals Metabolic Reprogramming of Double\u2010Negative, Na\u00efve, and Transitional Cell Subsets and Refines Molecular Classification in Sj\u00f6gren's Disease"],"prefix":"10.1002","volume":"56","author":[{"given":"Cristian","family":"Iperi","sequence":"first","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhiya Anilkumar","family":"Rekha","sequence":"additional","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"},{"name":"AltraBio SAS  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustav","family":"Arvidsson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Molecular Precision Medicine Uppsala University  Uppsala Sweden"},{"name":"Science For Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnel","family":"Nordmark","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Rheumatology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonore","family":"Bettacchioli","sequence":"additional","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"},{"name":"CHU De Brest  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Frutoso","sequence":"additional","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Alarc\u00f3n\u2010Riquelme","sequence":"additional","affiliation":[{"name":"GENYO, Centre for Genomics and Oncological Research Pfizer University of Granada, Andalusian Regional Government  Granada Spain"},{"name":"Institute for Environmental Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Nordlund","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Molecular Precision Medicine Uppsala University  Uppsala Sweden"},{"name":"Science For Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann\u2010Christine","family":"Syv\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Molecular Precision Medicine Uppsala University  Uppsala Sweden"},{"name":"Science For Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"PRECISESADS Flow Cytometry Study Group, PRECISESADS Clinical Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Devauchelle\u2010Pensec","sequence":"additional","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"},{"name":"CHU De Brest  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divi","family":"Cornec","sequence":"additional","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"},{"name":"CHU De Brest  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Hillon","sequence":"additional","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"},{"name":"CHU De Brest  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7886-2546","authenticated-orcid":false,"given":"Christophe","family":"Jamin","sequence":"additional","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"},{"name":"CHU De Brest  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bordron","sequence":"additional","affiliation":[{"name":"LBAI, UMR1227 Univ Brest, Inserm  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009742.2017.1324909"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66990-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2016.03.002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket427"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30381"},{"key":"e_1_2_11_7_1","first-page":"2434","article-title":"Lymphoepithelial Lesions in the Salivary Glands of Primary Sj\u00f6gren's syndrome Patients: The Perfect Storm?","volume":"40","author":"Pringle S.","year":"2022","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.03.012"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665\u20109913(23)00340\u20105"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.110"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665\u20109913(19)30042\u20106"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez335"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2015.07.002"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023472\u20107"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex490"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.06.046"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41610"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38628"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010019\u20100398\u2010x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010018\u20100010\u20106"},{"key":"e_1_2_11_21_1","first-page":"668","article-title":"STAT3 Phosphorylation Mediates the Stimulatory Effects of Interferon Alpha on B Cell Differentiation and Activation in SLE","volume":"59","author":"De Groof A.","year":"2020","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42683"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.6.554"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u201012\u2010323"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010016\u20101070\u20105"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.07.034"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21031"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.265249.120"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110243"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010019\u20101862\u20105"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.602539"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517\u20106161.1995.tb02031.x"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u201014\u2010128"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010018\u20104772\u20100"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14766-3"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010020\u201002248\u20102"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.7.3610"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42482"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.10.020"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102005\u201012\u20104788"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.02.009"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.12933"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000201"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42789"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6624"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3175"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.015"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2020.102439"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.70275","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.70275","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.70275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:52:24Z","timestamp":1790661144000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.70275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":50,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/eji.70275"],"URL":"https:\/\/doi.org\/10.1002\/eji.70275","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70275"}}