Search PubMed⌕ Search

Biomedical subjects

D Vergani

Publications and source records attributed to D Vergani.

229 records · Page 13Linked to original sources
PubMed1979

Lymphocyte cytotoxicity to autologous hepatocytes in HBsAg-negative chronic active hepatitis.

In a micrototoxicity assay, lymphocytes from ten out of sixteen patients with HBsAg-negative chronic active hepatitis have been shown to be cytotoxic to autologous hepatocytes isolated from percutaneous liver biopsies. This cytoxicity was demonstrable in all six untreated patients but in only four out of ten receiving immunosuppressive treatment, the presence of cytotoxicity showing a significant association with the activity of the disease assessed histologically. The addition of excess purified lipoprotein (LSP), derrived from the hepatocyte plasma membrane, blocked the reaction in all cytotoxic cases, indicating that LSP was the major target antigen. Enriched fractions of T cells were cytotoxic in only one case, whereas non-T cell fractions were cytotoxic in the other ten cases investigated in this way. For optimum T cell cytotoxicity, effector and target cells must share histocompatibility determinants and the results of this study using an autologous system show conclusively that the lymphocyte cytotoxicity found in HBsAg-negative chronic active hepatitis is mediated by a non-T cell population.

Adult↗
PubMed1978

Sensitisation to halothane-altered liver components in severe hepatic necrosis after halothane anaesthesia.

In-vitro sensitisation (inhibiton or stimulation of leucocyte migration) in response to a liver homogenate obtained from rabbits pretreated with halothane was found in eight of twelve patients with halothane-associated hepatitis. Sensitisation was not observed when the homogenates were obtained from animals pretreated with ether. Furthermore, leucocyte migration in response to "halothane homogenate" was normal in eleven patients who had shown no abnormality in liver function after halothane anaesthesia and in thirty patients with other liver diseases. These studies provide direct evidence that sensitisation to halothane-altered liver-cell components is present in those occasional patients in whom severe liver damage develops after halothane anaesthesia.

Adult↗
PubMed1978

Occurrence of circulating immune complexes in beta-thalassaemia major.

The presence of circulating soluble immune complexes and the level of complement were investigated in sera from 21 patients with beta-thalassaemia major, including both splenectomised and nonsplenectomised patients. A high level of immune complexes was found in half of these cases. Reduced complement levels were seen less frequently. There was no correlation between the presence of circulating immune complexes, decreased complement levels, and thpresence or absence of the spleen. The level of immune complexes increased with the age ofthe individual, i.e. with the duration of the disease.

Age Factors↗
PubMedDate not supplied

T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis.

To investigate the function of activated T lymphocytes in autoimmune chronic active hepatitis, 7 of 15 T-cell clones from the peripheral blood of 8 patients were studied. These clones showed specificity for liver-membrane antigen with proliferation when stimulated by rabbit liver cell membranes. 6 of these clones reacted with liver-specific lipoprotein complex, and 1 clone (and 3 subclones) responded to the asialoglycoprotein receptor (ASGPR), both known targets of immune attack in autoimmune chronic active hepatitis. 2 of these clones stimulated autologous B lymphocytes to produce liver-membrane-specific autoantibodies and antibody to the ASGPR. These results suggest that liver-membrane-specific activated T lymphocytes in peripheral blood may be important in the autoimmune attack of chronic active hepatitis.

Adolescent↗
PubMedDate not supplied

Virus, liver and autoimmunity.

The immune system's ability to distinguish self from nonself is essential for both host defence against microbial antigens and protection of self-antigens from autoimmune destruction. Such discrimination is complicated by extensive structural homology shared between micro-organisms and self-antigens, a condition known as molecular mimicry. Molecular mimicry provides the foundation for an immune response directed against an exogenous agent such as a virus to cross-react with mimicked host self sequences, leading to autoimmunity, and in some cases, tissue injury and autoimmune disease. In this review we analyse studies investigating the role of molecular mimicry and cross-reactive immunity in liver-related autoimmunity.

Animals↗
PubMedDate not supplied

Complement.

Explore the source record for details and available documents.

Animals↗
PubMedDate not supplied

Multiple viral/self immunological cross-reactivity in liver kidney microsomal antibody positive hepatitis C virus infected patients is associated with the possession of HLA B51.

Liver Kidney Microsomal autoantibody type 1(LKM1) directed to cytochrome P4502D6 (CYP2D6) characterises autoimmune hepatitis type-2 (AIH-2), but is also found in a proportion of chronic hepatitis C virus (HCV) infected patients, CYP2D6252-271 being a major B- cell autoepitope. Molecular mimicry and immunological cross-reactivity between CYP2D6252-271, HCV polyprotein and the infected cell protein 4 (ICP4) of herpes simplex virus type 1 (HSV-1) have been suggested as triggers for the induction of LKM1, but reactivity and cross-reactivity to the relevant sequences have not been investigated experimentally. CYP2D6252-271 and its viral homologues were constructed and tested by ELISA in the sera of 46 chronically infected HCV patients, 23 of whom were LKM1 positive. Reactivity to the E1 HCV and ICP4 HSV1 mimics was frequently found in HCV infected patients irrespectively of their LKM1 status; viral/self cross-reactivity (as indicated by inhibition studies), however, was present in the only 2 of the 23 LKM1 seropositive HCV patients, who possessed the HLA allotype B51. Our results indicate that in HCV infected patients virus/self cross-reactivity is dependent on a specific immunogenetic background, a finding awaiting confirmation by studies in larger series of patients.

Adult↗
PubMedDate not supplied

Alcohol dehydrogenase: an autoantibody target in patients with alcoholic liver disease.

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 beta2 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 (1/8, 13 %, P < 0.005), HBV infection (2/8, 25 %, P=0.03), non-alcohol related disease (9/29, 23 %, P < 0.0001) and in normal controls (3/22, 14 %, P < 0.0001); were more frequent in patients with cirrhosis than in those with steatosis (26/34, 76 % vs 34/64, 53 %, P=0.02); and were associated with elevated levels of ALT (anti-ADH beta2, P < 0.05), immunoglobulin A (P < 0.05) and gamma-glutamyl transpeptidase (P=0.01). Anti-ADH antibody positive serum samples were able to inhibit the enzymatic activity of ADH. These findings suggest that anti-ADH antibodies may be triggered by alcohol consumption and act as a disease activity marker in alcoholic liver disease.

Adult↗
PubMedDate not supplied

Autoimmune hepatitis.

Autoimmune hepatitis is an inflammatory liver disease in which the immune system is believed to orchestrate an immune attack onto the liver cell. Current knowledge suggests that both T helper 1 (TH1) and TH2 programmes are involved in the generation of the liver damage. Release of TH2 cytokines leads to the production of autoantibodies to the hepatocyte membrane that recruit killer cells. TH1 cytokines induce macrophage activation which contributes to hepatocyte destruction. Patients commonly possess the "autoimmune" HLA A1/B8/DR3 haplotype and a silent gene at the C4A locus with consequent partial deficiency of the complement component C4. Two main types of autoimmune hepatitis are recognised according to the presence of circulating non-organ specific autoantibodies. Patients with smooth muscle antibody and/or antinuclear antibody may be adults or children, while patients with antiliver kidney microsomal type 1 (LKM1) antibody are usually children or very young adults. In both types there is a preponderance of females. LKM1 antibody is also present in a proportion of adult patients, mainly male, with chronic hepatitis C virus infection. This observation originally led to the suggestion that hepatitis C virus may be the cause of this form of autoimmune hepatitis, but several studies have shown that the epitopes target of the LKM1 antibody in autoimmune hepatitis and chronic hepatitis C virus infection differ. Although autoimmune hepatitis responds satisfactorily to immunosuppression in the short term, progression to cirrhosis is frequent. It is hoped that ongoing research will provide a better understanding of the pathogenic mechanisms of liver damage leading to a more effective and specific mode of treatment.

Autoantibodies↗