Alcohol dehydrogenase: A target of humoral autoimmune response in liver disease

Ma, Yuanfang; Gäken, Joop; McFarlane, Barbara M.; Foss, Yvonne; Farzaneh, Farzin; McFarlane, I G; Mieli‐Vergani, Giorgina; Vergani, Diego

doi:10.1053/gast.1997.v112.pm9024302

Cited by 39 publications

(18 citation statements)

References 35 publications

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“…In the same study we noted that anti-ADH antibodies were present, at a prevalence similar to that seen in autoimmune liver disease (50%), in a small control group of patients with ALD and that observation triggered the present study (13).…”

supporting

confidence: 73%

“…We have previously reported that human alcohol dehydrogenase (ADH) is a component ofLSP and an autoantibody target in patients with autoimmune hepatitis (13). In the same study we noted that anti-ADH antibodies were present, at a prevalence similar to that seen in autoimmune liver disease (50%), in a small control group of patients with ALD and that observation triggered the present study (13).…”

supporting

confidence: 65%

“…Whether the humoral immune reaction to a key enzyme in ethanol metabolism such as ADH also contributes to the pathogenesis of alcoholic liver disease or is just a consequence of alcoholinduced liver damage remains to be established (13). The fact that ADH autoantibodies can be found in some 10% of the normal controls would suggest that they are not influential in the development of alcoholic liver disease.…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies to human ADH 132 subunit and horse liver ADH (17233, Sigma Aldrich, Poole, UK) were detected by immunoblot (13). In brief, ADH preparations were subjected to electrophoresis in 12% polyacrylamide mini gels (Bio-Rad Laboratories, Heme!…”

Section: Detection Of Anti-adh Antibodies By Immunoblotmentioning

confidence: 99%

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Alcohol Dehydrogenase: An Autoantibody Target in Patients with Alcoholic Liver Disease

Meregalli

Hodges

et al. 2005

Int J Immunopathol Pharmacol

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The link between alcohol consumption and liver disease is not direct and several factors including autoimmunity to hepatocyte components have been implicated. We have previously identified alcohol dehydrogenase (ADH) as an autoantigen in autoimmune liver disease and in a proportion of patients with alcoholic liver disease. The aim of the present study is to investigate the association between the presence of anti-ADH antibodies, alcohol consumption and severity of liver damage in alcoholic patients. The presence of antibodies to human ADH 132 and horse ADH was investigated in 108 patients with documented history of alcohol consumption and alcohol related liver disease, 86 being active alcohol abusers and 22 on sustained alcohol withdrawal, 39 with non-alcohol related disease and 22 normal subjects.Antibodies to either ADH form were more frequently detected in active alcohol abusers (55/86, 64%) than in patients on sustained alcohol withdrawal longer than 6 months (118, 13 %, P<0.005), HBV infection (2/8,25%, P=0.03), non-alcohol related disease (9/29, 23%, P

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supporting

confidence: 73%

supporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Detection Of Anti-adh Antibodies By Immunoblotmentioning

confidence: 99%

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Alcohol Dehydrogenase: An Autoantibody Target in Patients with Alcoholic Liver Disease

Meregalli

Hodges

et al. 2005

Int J Immunopathol Pharmacol

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“…It has also been shown that titres of anti-liver-specific membrane lipoprotein (LSP) antibody, as well as antibodies to the LSP components asialoglycoprotein receptor (ASGPR) and alcohol dehy- drogenase, correlate with biochemical and histological indices of disease severity [16][17][18] . Anti-soluble liver antigen (SLA) antibodies, targeting the UGA suppressor tRNA-associated antigenic protein (tRNP (Ser)Sec ), recently re-named SepSecS [19] and originally described by Manns et al [20] , are found in some 50% of patients with type 1 and type 2 AIH, where they define a disease course more severe than in anti-SLA-seronegative patients [21] .…”

Section: Humoral Immunitymentioning

confidence: 99%

Adaptive Immunity in Autoimmune Hepatitis

Longhi¹,

Ma²,

Mieli‐Vergani³

et al. 2010

Dig Dis

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The histological lesion of interface hepatitis, with its dense portal cell infiltrate consisting of lymphocytes, monocytes/macrophages and plasma cells, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of autoimmune hepatitis (AIH). Immunohistochemical studies, focused on the phenotype of inflammatory cells infiltrating the liver parenchyma, have shown a predominance of αβ-T cells. Amongst these cells, the majority have been CD4 helper/inducers, while a sizeable minority have consisted of CD8 cytotoxic/suppressors. Lymphocytes on non-T cell lineage included natural killer cells, monocytes/macrophages and B lymphocytes. For autoimmunity to arise, the self-antigenic peptide, embraced by an human leukocyte antigen (HLA) class II molecule, must be presented to an uncommitted T helper (T_H0) lymphocyte by professional antigen-presenting cells. Once activated and according to the presence in the milieu of interleukin 12 (IL-12) or IL-4, T_H0 lymphocytes can differentiate into T_H1 cells, which are pivotal to macrophage activation; enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack; and induce HLA class II expression on hepatocytes; or they can differentiate into T_H2 cells, which produce IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25^high regulatory T cells. Numerical and functional regulatory T cell impairment characterises AIH and permits the perpetuation of effector immune responses with ensuing persistent liver destruction. Advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen, cytochrome P450IID6 (CYP2D6), is known to enable characterisation of antigen-specific immune responses.

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Autoimmune Hepatitis

and¹,

Mieli‐Vergani²

2007

Textbook of Hepatology

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Alcohol dehydrogenase: A target of humoral autoimmune response in liver disease

Cited by 39 publications

References 35 publications

Alcohol Dehydrogenase: An Autoantibody Target in Patients with Alcoholic Liver Disease

Alcohol Dehydrogenase: An Autoantibody Target in Patients with Alcoholic Liver Disease

Adaptive Immunity in Autoimmune Hepatitis

Autoimmune Hepatitis

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