Case 36: Weight loss, abdominal pain and diarrhoea Flashcards
What are the 3 typical symptoms of coeliac disease?
Weight loss, abdominal pain and diarrhoea
What is the patients serum tested for for diagnosis of coeliac disease?
Antibodies against tissue transglutaminase-2 and de-amidated gliadin peptides
What antibody isotype is implicated in coeliac disease?
IgA
What antibody isotype will be assayed if the patient is IgA deficient?
IgG
Which genes are associated with Coeliac disease?
HLA-DQ2 and HLA-DQ8
What type sensitivity is coeliac disease?
Type IV
What percentage of coeliac patients are DQ2+ve?
> 90% - remainder DQ8 positive
What are patients with coeliac disease sensitive to?
Gliadins in wheat gluten
What are gliadins?
Alcohol soluble fraction of gluten that is glutamine rich
What does tissue transglutaminase do?
Deamidates free amino groups on glutamine residues on gliadin peptides, resulting in glutamine (+) → glutamate (-).
What do deamidated gliadins do once deamidated?
Bind efficiently to HLA-DW2 - because anchor is generated
What happens to deamidated gliadin peptides once bound to HLA-DQ2?
HLA-DQ2 presents gliadin peptides to gliadin-specific T cells
Which T cell is implicated in the immunopathology of coeliac disease?
Th1 T cell
Which cytokines are released in response to stimulation of Th1 T cell in coeliac disease?
Chemokines: recruitment to islet cells
IFN-gamma: macrophage release of inflammatory mediators
TNF-beta: tissue destruction, adhesion molecules on local blood vessels
IL3: monocyte production by bone marrow
What is determinant spreading?
Where an immune response against one antigen results in an autoimmune response against a linked antigen - hence why patients with coeliac disease not only make anti-gliadin Abs but also anti-tTg Abs.
