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Hepatobiliary Immunopathology

P.I.: Pietro Invernizzi, MD PhD

Research Activities Pietro Invernizzi Publications
Main results
 
Our group begun its research activities at the IRCCS Istituto Clinico Humanitas facilities in September 2008. For this reason, new onsite studies are currently ongoing and results are awaited in the next months. We foresee to continue on the same research lines that were followed over the past years which are witnessed by the publication since 2007 of over 25 peer-reviewed original articles, 25 review articles, 11 book chapters, and 3 limited-circulation manuscripts (including editorials or commentaries) co-authored by the components of the group. In brief, the obtained evidence includes the following research lines:
 
1. S ex chromosomes in autoimmunity
The role of sex chromosomes in the pathogenesis of female-predominant autoimmune diseases. In particular, our group was the first to propose the theory that a haploinsufficiency for X chromosome genes may cause autoimmunity secondary to X chromosome preferential loss. Of note, this theory seems to apply to different conditions sharing major clinical features thus providing new and exciting scenarios in the common grounds of autoimmune diseases.
 
2.   Genetics of primary biliary cirrhosis (PBC)
We coordinated over the past years the collection of the largest series of DNA from patients with PBC; this effort has most recently culminated in the ultimate study on HLA associations in this complex condition.
 
3.   Clinical significance of serum autoantibodies in PBC
We performed the first and largest cross-sectional and longitudinal studies to suggest the prognostic impact of anti-nuclear antibodies (ANA).
 
4.   Environmental factors in PBC
This is well represented by the largest questionnaire-based study for risk factors and comorbidities, as well as several experimental studies on the role of xenobiotics and infectious agents.
 
5.  Immunity and nutrition
We have recently initiated an effort to determine the role of nutritional factors on the immune function and chronic inflammation as observed on non alcoholic steatohepatitis.
 
 
Main objectives and research lines
 
Our ongoing / future research interests include
 
Pathogenesis of autoimmune liver diseases
Several studies have been completed or are ongoing on PBC to (i) determine the susceptibility bases through a genome-wide association study for single nucleotide polymorphisms; (ii) study DNA methylation, histone code, and micro RNA changes in patients with PBC with particular effort in the study of monozygotic twin sets discordant for PBC; (iii) determine T regulatory cell alterations in PBC; (iv) investigate the apoptosis features of bile duct cells in PBC, with particular attention to the modifications of the major autoantigens in these cells. Furthermore, we are attempting to establish new primary cholangiocyte cell lines to understand the role of the organ tissue target in the development of autoimmune cholangiopathies. We are also contributing to develop a new experimental model for autoimmune cholangiopathies, based on a transgenic models expressing a viral protein of the nucleoprotein of the lymphocytic choriomeningitis virus (LCMV) specifically in their cholangiocytes. We expect that infection of these models with LCMV would lead to a form of autoimmune cholangiopathies, because virus-cytotoxic T cells generated in the viral infection should also vigorously attack cholangiocytes.
 
Epidemiology of autoimmune liver diseases and study of new disease markers
We are performing a population-based study to determine the prevalence of serum autoantibodies and the natural history of autoimmune cholangiopathies. Towards the same aim, we plan to investigate the clinical and pathogenetic role of serum autoantibodies detected using new laboratory methods based on recombinant antigens. The role of serum micro RNA will be also evaluated.
 
Cholangiocarcinoma
We are performing studies on cholangiocarcinoma ranging from the identification of novel biomarkers (such as biliary IGF-1 levels and serum micro RNA) to the understanding of the main molecular and genetic defects possibly involved in this cancer development.
 
Metabolic syndrome

The role of dietary monosodium glutamate (MSG) in the pathogenesis of non alcoholic fatty liver disease and obesity. We have contributed to develop and have access to a new MSG-induced experimental model for the metabolic syndrome

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