Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder
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 transglutaminas...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13124 |
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| author | Onni Niemelä Aini Bloigu Risto Bloigu Ulla Nivukoski Johanna Kultti Heidi Pohjasniemi |
| author_facet | Onni Niemelä Aini Bloigu Risto Bloigu Ulla Nivukoski Johanna Kultti Heidi Pohjasniemi |
| author_sort | Onni Niemelä |
| collection | DOAJ |
| description | 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 (<i>n</i> = 83) or without (<i>n</i> = 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 (<i>p</i> < 0.0005 for tTG-IgA, <i>p</i> = 0.006 for Hb-Ach-IgA) or in healthy controls (<i>p</i> < 0.0005 for both comparisons). The HbAch-IgA levels in the alcoholics without liver disease also exceeded those found in healthy controls (<i>p</i> = 0.0008). In ROC analyses, anti-tTG-antibodies showed an excellent discriminative value in differentiating between ALD patients and healthy controls (AUC = 0.95, <i>p</i> < 0.0005). Significant correlations emerged between tTG-IgAs and HbAch-IgAs (r<sub>s</sub> = 0.462, <i>p</i> < 0.0005), CDT (r<sub>s</sub> = 0.413, <i>p</i> < 0.0001), GT (r<sub>s</sub> = 0.487, <i>p</i> < 0.0001), alkaline phosphatase (r<sub>s</sub> = 0.466, <i>p</i> < 0.0001), serum markers of fibrogenesis: PIIINP (r<sub>s</sub> = 0.634, <i>p</i> < 0.0001), hyaluronic acid (r<sub>s</sub> = 0.575, <i>p</i> < 0.0001), ICTP (r<sub>s</sub> = 0.482, <i>p</i> < 0.0001), pro-inflammatory cytokines IL-6 (r<sub>s</sub> = 0.581, <i>p</i> < 0.0001), IL-8 (r<sub>s</sub> = 0.535, <i>p</i> < 0.0001) and TNF-α (r<sub>s</sub> = 0.591, <i>p</i> < 0.0001), whereas significant inverse correlations were observed with serum TGF-β (r<sub>s</sub> = −0.366, <i>p</i> < 0.0001) and CTx, a marker of collagen degradation (r<sub>s</sub> = −0.495, <i>p</i> < 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. |
| first_indexed | 2024-03-10T23:22:47Z |
| format | Article |
| id | doaj.art-a051076055874c42b4de4fe90f6a5dad |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:22:47Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a051076055874c42b4de4fe90f6a5dad2023-11-19T08:12:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171312410.3390/ijms241713124Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use DisorderOnni Niemelä0Aini Bloigu1Risto Bloigu2Ulla Nivukoski3Johanna Kultti4Heidi Pohjasniemi5Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, 60220 Seinäjoki, FinlandResearch Unit of Population Health, Faculty of Medicine, University of Oulu, 90220 Oulu, FinlandInfrastructure of Population Studies, Faculty of Medicine, University of Oulu, 90220 Oulu, FinlandDepartment of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, 60220 Seinäjoki, FinlandDepartment of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, 60220 Seinäjoki, FinlandDepartment of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, 60220 Seinäjoki, FinlandRecent 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 (<i>n</i> = 83) or without (<i>n</i> = 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 (<i>p</i> < 0.0005 for tTG-IgA, <i>p</i> = 0.006 for Hb-Ach-IgA) or in healthy controls (<i>p</i> < 0.0005 for both comparisons). The HbAch-IgA levels in the alcoholics without liver disease also exceeded those found in healthy controls (<i>p</i> = 0.0008). In ROC analyses, anti-tTG-antibodies showed an excellent discriminative value in differentiating between ALD patients and healthy controls (AUC = 0.95, <i>p</i> < 0.0005). Significant correlations emerged between tTG-IgAs and HbAch-IgAs (r<sub>s</sub> = 0.462, <i>p</i> < 0.0005), CDT (r<sub>s</sub> = 0.413, <i>p</i> < 0.0001), GT (r<sub>s</sub> = 0.487, <i>p</i> < 0.0001), alkaline phosphatase (r<sub>s</sub> = 0.466, <i>p</i> < 0.0001), serum markers of fibrogenesis: PIIINP (r<sub>s</sub> = 0.634, <i>p</i> < 0.0001), hyaluronic acid (r<sub>s</sub> = 0.575, <i>p</i> < 0.0001), ICTP (r<sub>s</sub> = 0.482, <i>p</i> < 0.0001), pro-inflammatory cytokines IL-6 (r<sub>s</sub> = 0.581, <i>p</i> < 0.0001), IL-8 (r<sub>s</sub> = 0.535, <i>p</i> < 0.0001) and TNF-α (r<sub>s</sub> = 0.591, <i>p</i> < 0.0001), whereas significant inverse correlations were observed with serum TGF-β (r<sub>s</sub> = −0.366, <i>p</i> < 0.0001) and CTx, a marker of collagen degradation (r<sub>s</sub> = −0.495, <i>p</i> < 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.https://www.mdpi.com/1422-0067/24/17/13124alcoholic liver diseaseautoantibodiesbiomarkerfibrosisinflammationinterleukin |
| spellingShingle | Onni Niemelä Aini Bloigu Risto Bloigu Ulla Nivukoski Johanna Kultti Heidi Pohjasniemi Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder International Journal of Molecular Sciences alcoholic liver disease autoantibodies biomarker fibrosis inflammation interleukin |
| title | Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder |
| title_full | Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder |
| title_fullStr | Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder |
| title_full_unstemmed | Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder |
| title_short | Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder |
| title_sort | patterns of iga autoantibody generation inflammatory responses and extracellular matrix metabolism in patients with alcohol use disorder |
| topic | alcoholic liver disease autoantibodies biomarker fibrosis inflammation interleukin |
| url | https://www.mdpi.com/1422-0067/24/17/13124 |
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