{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:52:59Z","timestamp":1789602779635,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P36774\u2010B"],"award-info":[{"award-number":["P36774\u2010B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["I6835\u2010B"],"award-info":[{"award-number":["I6835\u2010B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["ZK81\u2010B"],"award-info":[{"award-number":["ZK81\u2010B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/05623\u20105"],"award-info":[{"award-number":["2022\/05623\u20105"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Aims<\/jats:title>\n Alcohol\u2010related liver disease (ALD) is associated with elevated blood immunoglobulin\u2010type M (IgM) levels and hepatic lipid peroxidation. Nevertheless, the functional relevance of systemic IgM targeting lipid peroxidation products during ALD is incompletely understood.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Levels of IgM and IgG recognising malondialdehyde\u2013acetaldehyde (MAA), as a hallmark epitope of lipid peroxidation, as well as complement factors were assessed in the serum of patients with ALD. The influence of alcohol abstinence on anti\u2010MAA IgM and IgG levels was determined in AUD patients. A chronic\u2010binge ethanol diet was given to mice deficient in sialic acid\u2010binding immunoglobulin\u2010like lectin G (\n Siglec\u2010G<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ), with specifically increased systemic IgM, and mice lacking soluble IgM (\n sIgM<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ), and their corresponding littermates. Furthermore, wildtype mice were injected with MAA\u2010binding IgM antibodies (LR04) or isotype control IgM during chronic\u2010binge ethanol feeding.\n Siglec\u2010G<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n bone marrow transplantation into wildtype or complement C3 deficient mice (\n C3<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n ) was performed to investigate the involvement of complement activation by elevated IgM in ALD.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Serum levels of anti\u2010MAA IgM positively correlated with ALD severity in humans. While mice lacking soluble IgM had less pronounced liver injury, increased circulating anti\u2010MAA IgM titers in\n Siglec\u2010G<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice associated with more hepatocellular damage after ethanol feeding than wildtypes. Similarly, mice receiving LR04 displayed elevated liver injury compared to control\u2010injected mice. Moreover, besides less hepatic neutrophil and macrophage content, and stellate cell activation than wildtypes, ethanol\u2010fed\n Siglec\u2010G<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n and LR04\u2010treated mice had increased hepatic C3b deposition. Mice deficient in C3 displayed ameliorated ethanol\u2010induced liver injury compared with controls, despite similarly high anti\u2010MAA IgM levels after\n Siglec\u2010G<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n bone marrow transplantation, suggesting complement\u2010dependent liver injury upon high anti\u2010MAA IgM. In line, levels of MAA\u2010binding IgM inversely correlated with C3c and C4 in serum of patients with ALD.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Elevated systemic IgM titres that recognise MDA facilitate complement recruitment, which enhances hepatocyte injury, thereby promoting alcohol\u2010associated liver disease.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.70356","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T12:59:26Z","timestamp":1758113966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IgM<\/scp>\n Antibodies Targeting Malondialdehyde Promote Complement\u2010Mediated Liver Injury in Alcohol\u2010Related Liver Disease"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6844-8878","authenticated-orcid":false,"given":"Dragana","family":"Rajcic","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9813-8555","authenticated-orcid":false,"given":"Beatriz Pereira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taras","family":"Baranovskyi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-9146","authenticated-orcid":false,"given":"Benedikt","family":"Simbrunner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna Vienna Austria"},{"name":"Christian\u2010Doppler Laboratory for Portal Hypertension and Liver Fibrosis Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3403-3372","authenticated-orcid":false,"given":"Benedikt S.","family":"Hofer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna Vienna Austria"},{"name":"Christian\u2010Doppler Laboratory for Portal Hypertension and Liver Fibrosis Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Hoebinger","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Duckova","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolina","family":"Papac\u2010Milicevic","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Listabarth","sequence":"additional","affiliation":[{"name":"Clinical Division of Social Psychiatry, Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Weber","sequence":"additional","affiliation":[{"name":"Clinical Division of Social Psychiatry, Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Vyssoki","sequence":"additional","affiliation":[{"name":"Clinical Division of Social Psychiatry, Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"},{"name":"Psychosocial Health Center ESRA Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Clinical Division of Social Psychiatry, Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Molecular Nutritional Science University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Bergheim","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Molecular Nutritional Science University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph J.","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-0017","authenticated-orcid":false,"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-3583","authenticated-orcid":false,"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna Vienna Austria"},{"name":"Christian\u2010Doppler Laboratory for Portal Hypertension and Liver Fibrosis Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Hendrikx","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0014-7"},{"issue":"4","key":"e_1_2_11_3_1","article-title":"Global Burden of Alcohol Use Disorders and Alcohol Liver Disease","volume":"7","author":"Rehm J.","year":"2019","journal-title":"Biomedicine"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00688-6"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000899"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.10.026"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000381"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69490-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0099-1"},{"issue":"4","key":"e_1_2_11_10_1","article-title":"Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects","volume":"6","author":"Teschke R.","year":"2018","journal-title":"Biomedicine"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v12.i7.332"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00744-4"},{"issue":"4","key":"e_1_2_11_13_1","first-page":"285","article-title":"Dangerous Byproducts of Alcohol Breakdown\u2014Focus on Adducts","volume":"27","author":"Tuma D. J.","year":"2003","journal-title":"Alcohol Research & Health"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1079\/PNS2006496"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI157780"},{"issue":"3","key":"e_1_2_11_16_1","first-page":"305","article-title":"Malondialdehyde as a Prognostic Factor in Alcoholic Hepatitis","volume":"52","author":"Perez\u2010Hernandez O.","year":"2017","journal-title":"Alcohol and Alcoholism"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/he.2000.5373"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.63"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9396-3"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2849"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28970"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.10.014"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.02.027"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0652-0"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100712"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15676"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2016.02.008"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1480"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.35"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.7683"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2023.03.026"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.11.033"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00579-3"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2021.05.007"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(01)00025-6"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-328265"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00334.2017"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1995.tb01020.x"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.14.6.451"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01536768"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000198223"},{"issue":"8","key":"e_1_2_11_42_1","first-page":"419","article-title":"Serum Levels of Immunoglobulins and Complement in Alcoholic Liver Disease","volume":"193","author":"Sopena B.","year":"1993","journal-title":"Revista Cl\u00ednica Espa\u00f1ola"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2002.5267"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890600664608"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.01.053"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.041"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-023-02229-w"},{"key":"e_1_2_11_48_1","article-title":"Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy","volume":"160","author":"Reiberger T.","year":"2020","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.12.022"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.032"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.06.004"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43228-0"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114511004983"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317232"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T16:41:59Z","timestamp":1765989719000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":53,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/liv.70356"],"URL":"https:\/\/doi.org\/10.1111\/liv.70356","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]},"assertion":[{"value":"2025-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70356"}}