# Changes upon the gluten-free diet of HLA-DQ2 and TRAFD1 gene expression in peripheral blood of celiac disease patients

## TL;DR

This study shows that while a gluten-free diet doesn't change HLA-DQ2.5 gene activity, it increases TRAFD1 gene expression, which may help reduce inflammation in celiac disease patients.

## Contribution

The study reveals that TRAFD1 gene expression increases during a gluten-free diet, suggesting a novel role in reducing gluten-induced inflammation.

## Key findings

- HLA-DQ2.5 mRNA expression did not significantly differ between active and treated celiac disease patients.
- TRAFD1 mRNA was more highly expressed in peripheral blood mononuclear cells from treated celiac disease patients.
- TRAFD1 transcripts increased in patients during longitudinal gluten-free diet treatment, indicating a role in downregulating inflammation.

## Abstract

Celiac disease (CD) is a chronic immuno-mediated enteropathy caused by dietary gluten in genetically susceptible individuals carrying HLA (Human Leukocytes Antigen) genes that encode for DQ2.5 and DQ8 molecules. TRAFD1 (TRAF-type zinc finger domain 1) is a gene recently found associated with CD and defined as a master regulator of IFNγ signalling and of MHC class I antigen processing/presentation. There is no specific drug therapy and the only effective treatment is the gluten-free diet (GFD). The great majority of celiac patients when compliant with GFD have a complete remission of symptoms and recovery of gut mucosa architecture and function. Until now, very few studies have investigated molecular differences occurring in CD patients upon the GFD therapy.

We looked at the expression of both HLA DQ2.5 and TRAFD1 risk genes in adult patients with acute CD at the time of and in treated patients on GFD. Specifically, we measured by qPCR the HLA-DQ2.5 and TRAFD1 mRNAs on peripheral blood mononuclear cells (PBMC) from the two groups of patients.

When we compared the HLA-DQ mRNA expression, we didn't find significant variation between the two groups of patients, thus indicating that GFD patients have the same capability to present gliadin antigens to cognate T cells as patients with active disease. Conversely, TRAFD1 was more expressed in PBMC from treated CD subjects. Notably, TRAFD1 transcripts significantly increased in the patients analyzed longitudinally during the GFD, indicating a role in the downregulation of gluten-induced inflammatory pathways.

Our study demonstrated that HLA-DQ2.5 and TRAFD1 molecules are two important mediators of anti-gluten immune response and inflammatory process.