{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:15:22Z","timestamp":1777709722218,"version":"3.51.4"},"reference-count":126,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Competitive State Research Financing of the Expert Responsibility area of Sein\u00e4joki Central Hospital and the University of Tampere","award":["VTR 6451 1051 7331"],"award-info":[{"award-number":["VTR 6451 1051 7331"]}]},{"name":"Competitive State Research Financing of the Expert Responsibility area of Sein\u00e4joki Central Hospital and the University of Tampere","award":["SKKY 04-2020"],"award-info":[{"award-number":["SKKY 04-2020"]}]},{"name":"Finnish Foundation for the Promotion of Laboratory Medicine 10-2014","award":["VTR 6451 1051 7331"],"award-info":[{"award-number":["VTR 6451 1051 7331"]}]},{"name":"Finnish Foundation for the Promotion of Laboratory Medicine 10-2014","award":["SKKY 04-2020"],"award-info":[{"award-number":["SKKY 04-2020"]}]},{"name":"Finnish Society of Clinical Chemistry","award":["VTR 6451 1051 7331"],"award-info":[{"award-number":["VTR 6451 1051 7331"]}]},{"name":"Finnish Society of Clinical Chemistry","award":["SKKY 04-2020"],"award-info":[{"award-number":["SKKY 04-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent data have emphasized the role of inflammation and intestinal immunoglobulin A (IgA) responses in the pathogenesis of alcoholic liver disease (ALD). In order to further explore such associations, we compared IgA titers against antigens targeted to ethanol metabolites and tissue transglutaminase with pro- and anti-inflammatory mediators of inflammation, markers of liver status, transferrin protein desialylation and extracellular matrix metabolism in alcohol-dependent patients with or without liver disease and in healthy controls. Serum IgAs against protein adducts with acetaldehyde (HbAch-IgA), the first metabolite of ethanol, and tissue transglutaminase (tTG-IgA), desialylated transferrin (CDT), pro- and anti-inflammatory cytokines, markers of liver status (GT, ALP) and extracellular matrix metabolism (PIIINP, PINP, hyaluronic acid, ICTP and CTx) were measured in alcohol-dependent patients with (n = 83) or without (n = 105) liver disease and 88 healthy controls representing either moderate drinkers or abstainers. In ALD patients, both tTG-IgA and HbAch-IgA titers were significantly higher than those in the alcoholics without liver disease (p &lt; 0.0005 for tTG-IgA, p = 0.006 for Hb-Ach-IgA) or in healthy controls (p &lt; 0.0005 for both comparisons). The HbAch-IgA levels in the alcoholics without liver disease also exceeded those found in healthy controls (p = 0.0008). In ROC analyses, anti-tTG-antibodies showed an excellent discriminative value in differentiating between ALD patients and healthy controls (AUC = 0.95, p &lt; 0.0005). Significant correlations emerged between tTG-IgAs and HbAch-IgAs (rs = 0.462, p &lt; 0.0005), CDT (rs = 0.413, p &lt; 0.0001), GT (rs = 0.487, p &lt; 0.0001), alkaline phosphatase (rs = 0.466, p &lt; 0.0001), serum markers of fibrogenesis: PIIINP (rs = 0.634, p &lt; 0.0001), hyaluronic acid (rs = 0.575, p &lt; 0.0001), ICTP (rs = 0.482, p &lt; 0.0001), pro-inflammatory cytokines IL-6 (rs = 0.581, p &lt; 0.0001), IL-8 (rs = 0.535, p &lt; 0.0001) and TNF-\u03b1 (rs = 0.591, p &lt; 0.0001), whereas significant inverse correlations were observed with serum TGF-\u03b2 (rs = \u22120.366, p &lt; 0.0001) and CTx, a marker of collagen degradation (rs = \u22120.495, p &lt; 0.0001). The data indicate that the induction of IgA immune responses toward ethanol metabolites and tissue transglutaminaseis a characteristic feature of patients with AUD and coincides with the activation of inflammation, extracellular matrix remodeling and the generation of aberrantly glycosylated proteins. These processes appear to work in concert in the sequence of events leading from heavy drinking to ALD.<\/jats:p>","DOI":"10.3390\/ijms241713124","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T08:57:39Z","timestamp":1692781059000},"page":"13124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder"],"prefix":"10.3390","volume":"24","author":[{"given":"Onni","family":"Niemel\u00e4","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Medical Research Unit, Sein\u00e4joki Central Hospital, 60220 Sein\u00e4joki, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aini","family":"Bloigu","sequence":"additional","affiliation":[{"name":"Research Unit of Population Health, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risto","family":"Bloigu","sequence":"additional","affiliation":[{"name":"Infrastructure of Population Studies, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulla","family":"Nivukoski","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Medical Research Unit, Sein\u00e4joki Central Hospital, 60220 Sein\u00e4joki, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Kultti","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Medical Research Unit, Sein\u00e4joki Central Hospital, 60220 Sein\u00e4joki, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Pohjasniemi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Medical Research Unit, Sein\u00e4joki Central Hospital, 60220 Sein\u00e4joki, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bala, S., Marcos, M., Gattu, A., Catalano, D., and Szabo, G. 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