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:
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.
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.
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).
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
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
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.
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