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D P Bogdanos

Publications and source records attributed to D P Bogdanos.

10 recordsLinked to original sources
PubMed2003

Association between the primary biliary cirrhosis specific anti-sp100 antibodies and recurrent urinary tract infection.

BACKGROUND AND AIMS: Recurrent urinary tract infections (rUTI) have been suggested to be involved in the induction of anti-mitochondrial antibodies (AMA), the serological hallmark of primary biliary cirrhosis (PBC), in view of the presence of AMA in rUTI women without liver disease and conversely of a high prevalence of rUTI in women with PBC. This prompted us to investigate whether PBC-specific anti-nuclear antibodies (ANA) to sp100, gp210 and lamin B receptor (LBR) antigens may also be related to rUTI. METHODS AND SUBJECTS: PBC-specific ANA reactivities were investigated in 20 women with rUTI but without liver disease, some of whom were AMA-seropositive; 40 women with PBC, with or without rUTI; and 104 pathological and 23 healthy controls. RESULTS: Among the women with rUTI but without liver disease, 8 (80%) of 10 AMA-positive women reacted with sp100 compared with none of the 10 AMA-negative women. Among the PBC patients, 14 (74%) of 19 with rUTI and 1 (4.8%) of the 21 without rUTI reacted with sp100. None of the rUTI women without liver disease reacted with gp210 or LBR. None of 127 pathological and healthy controls had PBC-specific ANA reactivity. CONCLUSIONS: Anti-sp100 reactivity strongly correlates with AMA seropositivity in rUTI women, with or without evidence of primary biliary cirrhosis. These findings provide additional support to the notion that E. coli infection is involved in the induction of PBC-specific autoimmunity. Additional factors must be involved in the progression to overt autoimmune disease.

Adult↗
PubMed2003

Mimicry between the hepatitis C virus polyprotein and antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis C virus infection.

Autoantibodies to smooth muscle (SMA) and nuclear components (ANA) arise in the natural course of chronic infection with hepatitis C virus. In view of the growing evidence for 'molecular mimicry' as a mechanism of autoimmunity we investigated whether cross-reactive immune reactions between host smooth muscle/nuclear components and HCV antigens may contribute to the formation of SMA and ANA in chronic HCV infection. Computer-assisted protein database search methods were used to identify three smooth muscle (smoothelin698-717, myosin1035-1054, vimentin69-88) and three nuclear (matrin722-741, histone H2A11-30, replication protein A133-152) host antigens with the highest local sequence similarity to the HCV polyprotein and 20-mer peptides corresponding to these regions were constructed. Sera from 51 children with chronic HCV infection [median age: 8 (2-16); 27 boys], 26 SMA positive and five ANA positive, were tested for reactivity to the synthesized HCV peptides and their human homologues by enzyme linked immunosorbent assay (ELISA). Sera from patients with HBV infection and chronic liver disease of different aetiologies were used as controls. 'Double reactivity' to HCV peptides and smooth muscle/nuclear homologues was associated strongly with HCV infection (P < 0.001 for both). Humoral cross-reactivity was established as the basis for double recognition by competition ELISA. Double-reactivity to smooth muscle and HCV peptide antigens correlated with SMA positivity by indirect immunofluouresence (P = 0.05). Of 15 patients double-reactive to myosin1035-1054 and its HCV homologue, 13 recognized whole myosin by immunoblot. These results suggest that ANA and SMA in chronic HCV infection may arise, at least in part, as a consequence of cross-reactive immune responses to HCV and host smooth muscle/nuclear antigens.

Adolescent↗
PubMed2001

Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences.

The pathogenesis of autoimmune liver disease and autoimmunity associated with chronic viral hepatitis remains poorly understood. One of the major hurdles to a deeper understanding of these pathological processes is the absence of clearly defined inductive mechanisms, which, if identified and characterised, could guide clinical strategies for their prevention or allow therapeutic intervention. Molecular mimicry leading to crossreactive autoimmune responses has gained strong experimental support in the past decade. A fundamental premise of this hypothesis is the involvement of a mimicking environmental trigger. In view of the numerous viral and bacterial agents epidemiologically linked to autoimmune liver diseases, we and others have proposed molecular mimicry to be an important mechanism in these diseases. We also propose similar crossreactive mechanisms to operate in the generation of autoimmunity in viral hepatitis. This review focuses on molecular mimicry at the level of the B-cell, as few data on T-cell crossreactivity in liver disease are thus far available.

Autoimmune Diseases↗
PubMed2001

Pediatric autoimmune liver diseases: the molecular basis of humoral and cellular immunity.

Pediatric autoimmune liver disease is mainly represented by two similar liver disorders: autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), both characterized by hypergammalobulinemia, interface hepatitis and the presence of a wide range of circulating autoantibodies. Although similar features are seen in AIH and inflammatory bowel disease, histological biliary changes are more common in ASC. In addition to their role as diagnostic markers, autoantibodies, such as anti-extractable nuclear antigen (ENA) antibodies and liver kidney microsomal antibody type 1 (LKM1) may be involved directly in inducing aggressive liver diseases. Although the cellular immune response in pediatric autoimmune liver disease has been less intensively investigated than humoral immunity, the importance of antigen specific T cells has been explored. Both alphabeta and gammadelta T cells derived from either peripheral blood and liver biopsies have highly heterogeneous TCR gene usage and cytolytic activity has been demonstrated. There have been attempts to seek triggers of liver autoimmunity and several sequences shared in common between autoantigens and hepatotropic viruses, namely hepatitis B, C and cytomegalovirus have been identified. The presence of cross-reactivity between homologous sequences, especially between HCV and cytochromes, supports the possibility that molecular mimicry plays a role in the induction of autoantibodies and autoreactive cytotoxic T cells.

Amino Acid Sequence↗
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

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↗