Colonic CD resembles UC more closely than ileal CD.

[kiny]

Characterisation of IBD heterogeneity using serum proteomics: A multicentre study.

European Union’s Horizon research
Örebro University, Sweden

2024 Nov

Background:
Recent genetic and transcriptomic data highlight the need for improved molecular characterisation of inflammatory bowel disease (IBD). Proteomics may advance the delineation of IBD phenotypes since it accounts for post-transcriptional modifications.

Aim:
We aimed to assess the IBD spectrum based on inflammatory serum proteins and identify discriminative patterns of underlying biological subtypes across multiple European cohorts.

Methods:
Using proximity extension methodology, we measured 86 inflammation-related serum proteins in 1551 IBD patients and 312 healthy controls (HC). We screened for proteins exhibiting significantly different levels among IBD subtypes and between IBD and HC. Classification models for differentiating between Crohn's disease (CD) and ulcerative colitis (UC) were employed to explore the IBD spectrum based on estimated probability scores.

Results:
Levels of multiple proteins, such as IL-17A, MMP-10, and FGF-19, differed (fold-change>1.2; FDR<0.05) between ileal vs colonic IBD. Using multivariable models, a protein signature reflecting the IBD spectrum was identified, positioning colonic CD between UC and ileal CD, which were at opposite ends of the spectrum. Based on area under the curve (AUC) estimates, classification models more accurately differentiated UC from ileal CD (median AUCs>0.73) than colonic CD (median AUCs<0.62). Models differentiating colonic CD from ileal CD demonstrated intermediate performance (median AUCs 0.67-0.69).

Conclusion:
Our findings in serum proteins support the presence of a continuous IBD spectrum rather than a clear separation of CD and UC. Within the spectrum, disease location may reflect a more similar disease than CD vs UC, as colonic CD resembled UC more closely than ileal CD.

 

[kiny]

Many studies are pointless because they do not properly differentiate disease subtypes. This then leads to confused GI and confused patients. Why does treatment work for person A but not for person B.

Pharmaceutical companies are partly responsible for this, because they want their medication to be as wildly prescribed as possible.

GI should be demanding from regulatotary bodies to get approval for every subtype separately. Patients should not be the guinea pigs who are forced to trial every other medication before one works. "Everyone responds differently" is baloney, data clearly shows that these subtypes and classifications are very important.

Instead of properly classifying these patients, they are regarded as treatment naive patients, where GI end up playing the lottery with patients and make them switch treatments every few months. GI and research needs to be forced to learn about these subtypes, and make individualized treatment recommendations based on subtypes.

 

[rollinstone]

Hopefully RFK jr is actually able to clear out the currption in big pharma and we can get some more effective and safer tailored treatments leading into a cure. Stem cell treatment for instance. Which has reported great response for fistulizing cd. I’m sure if it can resolve fistulas it would be even more effective in non fistulizing colonic or ileal cd.

This said, qu biologics have a test they do to determine if their ssi vaccine is likely to work. So things are headed in that direction but it’s all happening way too slowly.