T and B cell function in alcoholic liver disease

doi:10.1016/S0168-8278(86)80078-2

Journal of Hepatology

Volume 2, Issue 2, 1986, Pages 195-207

https://doi.org/10.1016/S0168-8278(86)80078-2 Get rights and content

Summary

Increased in vivo synthesis of immunoglobulin in patients with alcoholic liver damage has been attributed to direct activation of B cells, although other defects of lymphocyte function have been identified suggesting a more generalised defect. In the present study we have investigated the role of T cell regulation of immunoglobulin production in alcoholic liver disease analysed according to the presence or absence of alcoholic hepatitis. Spontaneous production of IgG and IgA was elevated and co-culture experiments confirmed hyper-reactivity of B cells, but also suggested impaired T cell function. Suppressor cell activity for IgG and IgA was impaired. Similarly, the response to pokeweed mitogen for IgG and IgA was defective, although this was more marked for secretion than for proliferation suggesting an associated T helper defect. No differences in the immunological abnormalities were identified between those with alcoholic hepatitis and those with other alcoholic liver diseases. This study demonstrates a broad defect of T cells and a hyper-reactivity of B cells in patients with alcoholic liver disease, irrespective of the severity of hepatic inflammation.

References (24)

ZettermanR.K. et al.
Immunologic aspect of alcoholic liver disease
Gastroenterology
(1981)
KanagasundaramN. et al.
Alcoholic hyalin antigen (AHAg) and antibody (AHAb) in alcoholic hepatitis
Gastroenterology
(1977)
ZettermanR.K. et al.
Alcoholic hepatitis — Cell mediated immunological response to alcoholic hyalin
Gastroenterology
(1976)
KawanishiH. et al.
Impaired Concanavalin A inducible suppressor T-cell activity in active alcoholic liver disease
Gastroenterology
(1981)
AlexanderG.J.M. et al.
Contrasting relations between suppressor cell function and suppressor cell number in chronic liver disease
Lancet
(1983)
PerperasA. et al.
Autoimmunity to a liver membrane lipoprotein and liver damage in alcoholic liver disease
Gut
(1981)
SorrellS. et al.
Lymphocyte transformation and alcoholic liver injury
Gastroenterology
(1972)
SnyderN. et al.
Depressed delayed cutaneous hypersensitivity in alcoholic hepatitis
Amer. J. Dig. Dis.
(1978)
IturriagaH. et al.
Serum immunoglobulin-A changes in alcoholic patients
Ann. Clin. Res.
(1977)
WandsJ.R. et al.
In vitro studies of enhanced IgG synthesis in severe alcoholic liver disease
Clin. Exp. Immunol.
(1981)

StoboJ.D.

Cirrhosis and hypergammaglobulinaemia

Dig. Dis. Sci.

(1979)

LelbachW.K.

Organic pathology related to volume and pattern of alcohol use

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According to the study liver conditions are a significant risk factor for cryptococcal infection. Therefore, cryptococcal isolation and antifungal susceptibility testing, as well as appropriate antifungal drug use, should be studied and paid attention too.
Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis
2021, JHEP Reports
Citation Excerpt :
Such co-expressed gene groups (with fixed gene membership) have been identified as blood transcriptome modules (BTMs). In previous studies, the activity of each BTM module has been taken as the mean value of its member genes.9,10 In the current study, results of PBMC transcriptomics obtained by RNA sequencing (RNA-seq) were used to determine if there were broad immunological differences discernible at the baseline, to identify patients who would eventually respond or not respond to steroid therapy.
In patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who cannot (steroid-non-responders [NR]); 2 groups with different outcomes.
We performed RNA-seq analysis in PBMCs from 32 patients with definite SAH, at baseline and after 7 days of corticosteroids. The data were sorted into R and NR (n = 16, each group) using the Lille model and 346 blood transcription modules (BTMs) were identified. BTMs are predefined modules of highly co-expressed PBMC genes, which can determine specific immune cell types and cellular functions. The activity of each BTM was taken as the mean value of its member genes.
At baseline, 345 BTMs had higher activity (i.e. were upregulated) in NR relative to R. The 100 most upregulated BTMs in NR, included several modules related to lymphoid lineage (T, B, and natural killer [NK] cells), modules for cell division and mitochondrial respiratory electron transport chain (ETC, relating to energy production), but only a few modules of myeloid cells. Correlation studies of BTM activities found features of significantly greater activation/proliferation and differentiation for T and B cells in NR relative to R. After 7 days of corticosteroids, NR had no significant changes in BTM activities relative to baseline, whereas R had downregulation of BTMs related to innate and adaptive immunity.
At baseline and during corticosteroid therapy, increased activity in the PBMCs of gene modules related to activation/proliferation and differentiation of T and B cells, NK cells, and mitochondrial ETC, is a hallmark of SAH patients who are steroid-non-responders.
Patients with severe alcoholic hepatitis receive steroid therapy as the main line of treatment; however, this treatment is ineffective in some patients. This only becomes apparent after 7 days of steroid therapy. We have developed an approach where it can be estimated if a patient is going to respond or not to steroid therapy using the gene expression information of blood cells. This method will allow clinicians to assess the response of patients to steroids earlier, and will help them in adopting alternate strategies if the treatment is found to be ineffective in a particular patient.
The effects of alcohol on immunity and bacterial infection in the lung
2006, Medecine et Maladies Infectieuses
Citation Excerpt :
In alcoholic patients, circulating numbers of B cells are not significantly altered [31]. However, elevated levels of serum antibody or immunoglobulin (Ig), particularly those of the IgG and IgA subclasses, have been identified supporting the hypothesis for a shift toward Th2 mediated immune function at the expense of Th1 responses in the alcohol-abusing population [32]. Alcoholic patients are uniquely susceptible to lung infections.
When faced with invading pathogens that can lead to infection, patients must mount an effective and appropriate immune response. Altered immune function in patients who abuse alcohol has long been described in the medical literature. The alcohol-consuming host is particularly prone to infections in the lung, including bacterial pneumonia and tuberculosis. Over the last several decades, there has been increased interest in the immune mechanisms that underlie the increased risk of infection observed in this population. This article will review the basic immunology involved in the host response to an infection and then describe how alcohol disrupts many of these immune mechanisms. It will further provide an overview of lung infections which have been linked to alcohol abuse, and finally, it will address the evolving therapeutic approaches of the immune system that are being advanced to assist in caring for immunosuppressed hosts.
Lorsqu'ils sont confrontés à des pathogènes invasifs qui peuvent provoquer une infection, les patients doivent réagir par une réponse immunitaire efficace et appropriée. Les patients alcooliques ont une fonction immunitaire altérée depuis longtemps décrite dans la littérature médicale. Le malade alcoolique est particulièrement sensible aux infections pulmonaires, comprenant entre autres les pneumonies bactériennes et la tuberculose. Ces dernières décennies, il y a eu un regain d'intérêt en ce qui concerne les mécanismes immunitaires et le risque accru d'infection observé dans cette population. Cet article révise l'immunologie de base impliquée dans la réponse immunitaire de l'hôte face à une infection et décrit ensuite comment l'alcool altère plusieurs de ces mécanismes immunitaires. Ensuite, cet article propose une revue des infections pulmonaires reliées à l'alcoolisme et enfin il traite des nouvelles approches thérapeutiques du système immunitaire qui sont en développement afin de soigner l'hôte immunodéprimé.
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Cellular immune depression is linked to high mortality in sepsis, but has yet to be systematically analysed in liver cirrhosis. The aim of the present study was to directly compare functional immune parameters in patients with acute on chronic liver failure (ACLF), severe sepsis, and non-decompensated cirrhosis.
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Alcoholic hepatitis is a rate-limiting step in the development of alcoholic liver disease into liver cirrhosis, and approximately half of the heavy drinkers with alcoholic hepatitis develop liver cirrhosis within 5 years. Immunologic mechanisms may be involved in the individual differences in the clinical course of this disease. Endotoxin from the intestine seems to play an important role in neutrophil infiltration of the liver, which induces, and at the same time is induced; by cytokines and chemokines. Kupffer cells and monocytes also have a key role in activating other cell types and producing several cytokines, chemokines, and free radicals. Both cytokines and chemokines up-regulate expression of various adhesion molecules, and adhesion molecules accelerate a cell-to-cell contact that stimulates cytotoxic lymphocytes to cause hepatocyte death. Self-antigens and adducts formed as a result of the degenerative effect of ethanol or aldehyde are targets of antibody-dependent cell-mediated cytotoxicity. Oxygen radicals, NF-kB, and AP-1 are key intracellular factors mediating hepatocyte death in alcoholic hepatitis. Viral infections and alcoholic hepatitis exacerbate each other. Integration of both human investigations and accumulated information from various animal models will gradually clarify the immunological mechanism of alcoholic hepatitis in future.
DIFFERENTIAL CYTOKINE PROFILES in PATIENTS with VIRAL and NON-VIRAL RELATED LIVER CIRRHOSIS
2021, Bulletin of Pharmaceutical Sciences. Assiut

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Research PaperT and B cell function in alcoholic liver disease

Summary

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Lancet

Autoimmunity to a liver membrane lipoprotein and liver damage in alcoholic liver disease

Gut

Lymphocyte transformation and alcoholic liver injury

Gastroenterology

Depressed delayed cutaneous hypersensitivity in alcoholic hepatitis

Amer. J. Dig. Dis.

Serum immunoglobulin-A changes in alcoholic patients

Ann. Clin. Res.

In vitro studies of enhanced IgG synthesis in severe alcoholic liver disease

Clin. Exp. Immunol.

Cirrhosis and hypergammaglobulinaemia

Dig. Dis. Sci.

Organic pathology related to volume and pattern of alcohol use

Research Paper
T and B cell function in alcoholic liver disease