Early onset IBD Flashcards
Why are twins useful?
monozygotic concordant dizygotic not, the genetic factor is greater.
what are features would you see in early-onset (mendelian) IBD vs polygenic IBD (Crohn’s and UC)
Under 10 yo for sure
pancolitis
syndromic features and complications
(unusual infections)
examples of aspects of the gut and immune system where things going wrong can lead to early-onset IBD?
epithelial/barrier defects (TTC7A and guanylyl cyclase mutation)
Th1/Th17 skew (caused by high salt diet?)
phagocytic defects (e.g. neutrophils CGD)
immune suppression (FoxP, IL-10, TGF-B and XIAP)
What inflammatory pathways does IL-10 infringe upon?
Signals through Ty2 and JAK1
Inhibits NFKB production.
Inhibits STAT4 (downstream of IL-12)
What can be a complication of an IL10/Ra/B deficiency?
diarrhoea and B cell lymphoma.
Apart from IL-10, what other defect in an inflammatory cytokine can cause IBD? What other syndromic associations?
defect in TGF-B, presents with IBD, lymphoma and congenital brain abnormalities.
What could cause early-onset IBD, along with abscesses and lung infection?
defects in neutrophil phagocytosis (CGD), impaired killing leads to increased inflammation.
Impaired responses to bacteria (particularly catalase-positive, and e.g. aspergillus).
What condition that also is associated with HLH can cause IBD?
XIAP deficiency
What pathways does XIAP normally play a role in?
XIAP normally helps stimulate NOD2, and inhibits T cell apoptosis and inflammasome.
Deficiency causes increased microbial load and persistent inflammasome activation and hyperactivation.
which monogenic disease-causing IBD is mainly associated with neurodegenerative problems?
Niemann Pik type C
What defects are seen in Niemann Pick type C?
Higher microbial load due to lack of LC3 coating and autophagy.
What mutation of a gene expressed in the epithelium is associated with epithelial barrier disorganization and breaking away?
TTR7A- disorganisation of epithelium and increased falling away of it.
What could the congenital cause of diarrhoea be that doesn’t affect the immune system?
defect in a Na+/H+ pump, causing lack of Na2+ entry and osmolarity imbalance.
Or guannylyl cylase mutation. this can constitutively inhibit the sodium/H channel (like what enterotoxins can also do).
what can cause Il-17 skewing in western populations?
High salt diet (or pump defects causing Na2+ in lumen) leads to changes in the microbiome and tryptophan metabolism that may skew towards Th17 activation.
what might you screen for annually in patients with early-onset diarrhoea because of XIAP and Il-10/TGF-B deficiency?
Screen for EBV and or B cell lymphoma.
