Predictive risk markers in alcoholism

Niemelä, Onni

doi:10.1016/bs.acc.2023.05.002

Cited by 3 publications

(4 citation statements)

References 403 publications

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“…Interestingly, the present data also show significant correlations between anti-tTG antibodies and desialylated transferrin even in alcohol consumers without liver disease. A lack of sialic acid residues in transferrin is known as a highly specific feature of chronic heavy drinking [32]. On the other hand, studies in patients with IgA nephropathy, which is also a possible unfavorable outcome of heavy alcohol intake [9], have indicated that aberrant glycosylation and sialic acid deficiency in proteins is a typical characteristic of the neoantigens capable of inducing IgA responses and nephritogenic immune complexes [31].…”

Section: Discussionmentioning

confidence: 99%

“…The ECM synthesis markers were strongly associated with pro-inflammatory cytokines, whereas TGF-β, which has pleiotropic effects in the developmentof fibrosis in alcoholics [116,117], showed a negative association. The development of liver fibrosis in AUD patients constitutes a major determinant of prognosis and is characterized by significant alterations in both the amount and composition of the ECM [32,40,41,44,118,119]. ECM protein secretion can be stimulated by the activation of hepatic stellate cells as a result of inflammation and the generation of toxic metabolic products of ethanol [40,[120][121][122][123].…”

Section: Discussionmentioning

confidence: 99%

“…The status of tTG expression also seems to be important for IgA tissue binding [29,30]. Recent studies in patients with IgA nephropathy have suggested that the generation of disease-specific IgAs may also be associated with aberrant protein glycosylation and sialic acid deficiencies in proteins [31], which is also known as a distinguishing characteristic of patients with chronic alcohol abuse [32].…”

Section: Introductionmentioning

confidence: 99%

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Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder

Niemelä,

Bloigu,

Bloigu

et al. 2023

IJMS

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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 < 0.0005 for tTG-IgA, p = 0.006 for Hb-Ach-IgA) or in healthy controls (p < 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 < 0.0005). Significant correlations emerged between tTG-IgAs and HbAch-IgAs (rs = 0.462, p < 0.0005), CDT (rs = 0.413, p < 0.0001), GT (rs = 0.487, p < 0.0001), alkaline phosphatase (rs = 0.466, p < 0.0001), serum markers of fibrogenesis: PIIINP (rs = 0.634, p < 0.0001), hyaluronic acid (rs = 0.575, p < 0.0001), ICTP (rs = 0.482, p < 0.0001), pro-inflammatory cytokines IL-6 (rs = 0.581, p < 0.0001), IL-8 (rs = 0.535, p < 0.0001) and TNF-α (rs = 0.591, p < 0.0001), whereas significant inverse correlations were observed with serum TGF-β (rs = −0.366, p < 0.0001) and CTx, a marker of collagen degradation (rs = −0.495, p < 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder

Niemelä,

Bloigu,

Bloigu

et al. 2023

IJMS

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“…Future studies could benefit from including other diagnostic modalities, such as EEG [ 127 ]. Recent advances in clinical chemistry have revealed novel approaches for the specific detection of AUD through assays of phosphatidyl ethanol (PEth) or ethyl glucuronide (EtG), carbohydrate-deficient transferrin (CDT), and unique ethanol metabolites [ 128 ]. Other in vitro findings indicate the effect of ethanol and acetaldehyde on the level of peripheral oxidative stress markers—products of oxidative modification of lipids (lipid peroxidation products), DNA (8-hydroxy-2-deoxyguanosine, 8-OHdG), and proteins (protein carbonyls) in blood plasma.…”

Section: Future Directionmentioning

confidence: 99%

Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal

Malewska-Kasprzak,

Skibińska,

Dmitrzak-Węglarz

2024

Brain Sciences

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Background: Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). Currently, studies do not support using any one biomarker in DTs. Neurotrophins affect neuromodulation, playing a role in the pathogenesis of AUD, AWS, and DTs. Methods: This review aims to summarize experimental and clinical data related to neurotrophins and S100B in neuroplasticity, as well as neurodegeneration in the context of AUD, AWS, and DTs. This work used publications that were selected based on the protocol consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Results: The BDNF level could be a good candidate biomarker for relapse susceptibility, as it is significantly reduced during consumption and gradually increases during abstinence. GDNF influences AUD through its integral role in the function of dopaminergic neurons and ablates the return to alcohol-drinking behavior. NGF protects neurons from ethanol-induced cytotoxic damage and affects recovery from cognitive deficits after brain damage. The NT-3 level is decreased after alcohol exposure and is involved in compensatory mechanisms for cognitive decline in AUD. NT-4 affects oxidative stress, which is associated with chronic alcohol consumption. S100B is used as a biomarker of brain damage, with elevated levels in serum in AUD, and can protect 5-HT neurons from the damage caused by alcohol. Conclusions: BDNF, GDNF, NT-3, NT-4, NGF, and S100B may be valuable markers for withdrawal syndrome. In particular, the most relevant is their association with the development of delirium complications. However, there are few data concerning some neurotrophins in AWS and DTs, suggesting the need for further research.

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Role of glycogen synthase kinase-3β in dependence and abuse liability of alcohol

Oka,

Yoshino,

Kitanaka

et al. 2023

Alcohol and Alcoholism

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Background Alcohol is a major abused drug worldwide that contributes substantially to health and social problems. These problems result from acute alcohol overuse as well as chronic use, leading to alcohol use disorder (AUD). A major goal of this field is to establish a treatment for alcohol abuse and dependence in patients with AUD. The central molecular mechanisms of acute alcohol actions have been extensively investigated in rodent models. Aims One of the central mechanisms that may be involved is glycogen synthase kinase-3β (GSK-3β) activity, a key enzyme involved in glycogen metabolism but which has crucial roles in numerous cellular processes. Although the exact mechanisms leading from acute alcohol actions to these chronic changes in GSK-3β function are not yet clear, GSK-3β nonetheless constitutes a potential therapeutic target for AUD by reducing its function using GSK-3β inhibitors. This review is focused on the correlation between GSK-3β activity and the degree of alcohol consumption. Methods Research articles regarding investigation of effect of GSK-3β on alcohol consumption in rodents were searched on PubMed, Embase, and Scopus databases using keywords “glycogen synthase kinase,” “alcohol (or ethanol),” “intake (or consumption),” and evaluated by changes in ratios of pGSK-3βSer9/pGSK-3β. Results In animal experiments, GSK-3β activity decreases in the brain under forced and voluntary alcohol consumption while GSK-3β activity increases under alcohol-seeking behavior. Conclusions Several pieces of evidence suggest that alterations in GSK-3β function are important mediators of chronic ethanol actions, including those related to alcohol dependence and the adverse effects of chronic ethanol exposure.

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Predictive risk markers in alcoholism

Cited by 3 publications

References 403 publications

Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder

Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder

Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal

Role of glycogen synthase kinase-3β in dependence and abuse liability of alcohol

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