Autoimmune liver and pancreatic disease Flashcards
What cells are targeted in autoimmune hepatitis (AIH) and what markers
Associated with hepatocellular inflammation and necrosis where hepatocytes are targeted- leads to fibrosis and scarring.
Associated with autoantibodies against smooth muscles antigens (SM) and anti-nuclear antibodies.
what does PBC stand for and the features of this disease?
primary biliary cholangitis?
slow and progressive destruction of the small bile ducts- leads to cholestasis (bile duct flow blocked) and cirrhosis.
what does PSC stand for and what features? What IBD associated with this?
primary sclerosing cholangitis
chronic progressive destruction of large and small bile ducts which can be intra and extrahepatic (pancreas and gall bladder)
What is targeted in IgG4 disease?
intra and extra hepatic small and large bile ducts, inflammation, but less cirrhosis involved.
hepatocytes also targeted.
what antibodies are associated with AIH?
smooth muscle Ab and ANAs.
are bile ducts affected in AIH? And what gender and age groups mostly present with it?
Bile ducts aren’t blocked (bilirubin normal)
females more likely affected and biphasic presentation., adolescence and older age group.
non-specific and more specific clinical symptoms of AIH?
non-specific: joint pain and fatigue (when diagnosed often scarring is seen).
specific: yellowing, abdominal pains, itchiness
What are the type I and type II antibodies for AIH?
type 1: ANAs and SMab (against filamentous actin).
type 2: liver microsomal ab
anti-LC1 (FTCD)
anti LKM1 (CYP2D6)
Do AIH antibodies cause disease?
not thought to because they are intracellular, non-specific to hepatocytes but maybe useful for type II AIH models.
Where are necro inflammatory regions often seen in AIH?
In portal, periportal lesions- interface hepatitis.
what infiltrating cells are particularly prominent in AIH?
CD4 T cells and CD20 B cells and CD138+ plasma cells.
What structures do inflamed hepatocytes form in AIH?
rosettes in the area of interface hepatitis.
what is emperipolesis seen in AIH?
Where CD8 cells are in the cytoplasm of the damaged hepatocyte.
Are there any specific cells responsible for AIH pathogenesis?
Not really, basically said Th1 Th2 Th17 macrophages (TNFa IL-1) and plasma cells and even NK cell ADCC could be involved?
What is interesting about Treg cells in AIH?
Tregs are reduced in number in blood and intrahepatic tissue during active disease.
With treatment Tregs increase.
What can Il-2 deficicency within liver tissue show in an vitro liver model?
Tregs are suceptible to deficiency in Il-2, Treg apoptosis.
What effects can administration of IL-2 in in vitro liver models have?
low doses expand and activates Tregs.
High doses will activate T effector cells.
What Treg restoration technique is there apart from IL-2 administration?
Adoptive cell transfer: autologous Treg expansion and reintroduction.
What effect does rituximab have in AIH type II murine model?
Doesn’t reduce IgG.
But does reduce Tfh
and reduces the pro-inflammatory profile of B cells.
Reductino in inflammatory infiltrate.
Improvements seen in rituximab therapy in patients?
auto IgG ab decreased, ALT improved, inflammation grade fell in biopsies.
Alternative B cell targets in autoimmunity to rituximab?
anti BAFF/APRIL or BAFFR/TACI/ BCMA receptors
and Syk (fostamatibinib) and Btk
or indirectly via T cell costimulation (CTLA-4/ CD40/40L ICOSL)..
Non specific therapies to autoimmunity?
ciclospoirin, tacrolimus, corticosteroids mycophenolic acid azathioprine 6- mercaptopurine.
What does increased bilirubin and ALT, ALp and CRP imply?
they have a disease that is affecting the bile ducts and hepatocytes along with inflammation (ie IgG4 disease).
What common morphological features fo IgG4 disease are there?
inflammatory masses and strictures.