[Celiac disease: Novel pharmacological therapies]

[helvella]

With the current gluten/coeliac discussions, this paper (abstract only, I'm sorry to say), might be of some interest.

I note this sentence in particular:

The prerequisite for the development of coeliac disease is the carrier status for HLA-DQ2 or DQ8...

Which for the lucky few who know might help.

[Celiac disease: Novel pharmacological therapies].

Schuppan D , Neufang S , Wanger B

Deutsche Medizinische Wochenschrift (1946), 21 Feb 2025, 150(6):273-279 Language:ger

doi.org/10.1055/a-2318-8624 PMID: 39983762

Review

Abstract

Coeliac disease is the most common chronic inflammatory disease of the small intestine, with a prevalence of around 1% almost worldwide. It is caused by the consumption of cereals containing gluten (wheat, spelt, rye, barley). The initial diagnosis is made in equal proportions in children and adults. Classic symptoms are abdominal pain, diarrhea, malabsorption with anemia or osteoporosis, weight loss, and in children failure to thrive. Non-specific symptoms such as poor performance, headaches and joint pain are also common. Often undetected and untreated, coeliac disease can lead to serious complications, and up to 30% of adult coeliac patients suffer from associated autoimmune diseases, including thyroid and rheumatoid diseases or type 1 diabetes. The pathogenesis of coeliac disease is well studied. Incompletely digested gluten peptides reach the immune system of the intestinal mucosa and activate glute-reactive T cells, which lead to inflammation and atrophy of the absorptive villi. The prerequisite for the development of coeliac disease is the carrier status for HLA-DQ2 or DQ8, as well as the enzyme and coeliac disease autoantigen transglutaminase-2 expressed in the intestine, which modifies the gluten peptides by deamidation and thus increases their binding to HLA-DQ2/DQ8 and subsequent T-cell activation. Despite the gluten-free diet, 30-50% of diagnosed patients continue to suffer from symptoms with signs of inflammation, partly due to unavoidable minimal gluten contamination in everyday life. Supportive pharmacological therapy is therefore urgently needed. Promising therapeutic approaches are currently in clinical phase 2 development, including an inhibitor of intestinal TG2, blocking antibodies against interleukin-15 or Ox40 ligand, the improvement of the intestinal barrier using a sirtuin-6 agonist, as well as nanoparticular therapies that can induce tolerance to gluten by addressing the spleen or liver.

Paywall and, I think, main article is in German.

europepmc.org/article/MED/3...

[RedApple Administrator]

When our GPs request a test for coeliac disease, is it this carrier status for HLA-DQ2 or DQ8 that is being looked for?

[helvella Administrator in reply to RedApple]

An excellent question.

No:

A GP will arrange a blood test to check for antibodies usually present in the blood of people with coeliac disease.

nhs.uk/conditions/coeliac-d...

Possibly also having endoscopy, and a biopsy (through the endoscope).

There's a bit more detail here:

Coeliac Disease Tests

Gluten-Sensitive Enteropathy Tests

...

Total immunoglobulin A (IgA) and IgA Anti-tissue Transglutaminase Antibody (tTG) are usually the first choice tests performed for diagnosis of coeliac disease. IgA deficiency is significantly more common in people with coeliac disease in general population. That may give a false negative result when tested for IgA tTG, which may lead to a missed diagnosis. That explains the main reason for performing these two tests together If the results of the tests described above are uncertain, then the next test that may be performed is IgA antiendomysial antibody (EMA). This can be a helpful test when the IgA tTG result is weakly positive.

...

labtestsonline.org.uk/tests...

The HLA-DQ2/DQ8 bit is far beyond what I can get my head around! The Wiki article is pretty difficult to read - let alone understand. But it might provide some idea of what it is about:

HLA-DQ

en.wikipedia.org/wiki/HLA-DQ

[EchoWS]

Found a paper is on dermatitis herpetiformis as a form of celiac disease. HLA-DQ2 and HLA-DQ8 mentioned. Interesting change going on - I had a dr who I saw recently who marked me as celiac because of gluten sensitive skin rash and HLA-DQ8. (I did a test 15years ago). Celiac websites now seem to be talking about different variants of celiac disease which all require a gluten free diet. The link between hypothyroidism and celiac disease in second paper - which is very dense!

pmc.ncbi.nlm.nih.gov/articl...

pmc.ncbi.nlm.nih.gov/articl...

[helvella Administrator in reply to EchoWS]

Thank you - appreciated.

I get the feeling it is me who is dense when it comes to trying to get my head around all of this. So help such as your links is appreciated.