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P762 Gene expression profiling of immune adaptive response in the colonic mucosa from patients with ulcerative colitis

Fonseca Camarillo G., Iturriaga Goyon E., Yamamoto Furusho J.K.

Instituto Nacional de Ciencias Médicas y Nutriciόn Salvador Zubiran, Inflammatory Bowel Disease Clinic. Department of Gastroenterology, Mexico City, Mexico

Background

Ulcerative Colitis (UC) is caused by an aberrant immune response. Recent advances highlight the crucial role of the ubiquitination pathway dependent autophagy targeting of intracellular pathogens has implications for regulation of inflammatory responses.

Methods

We studied a total of 100 patients with definitive diagnosis of UC (50 active and 50 in remission) and healthy control group (50 subjects) without endoscopic evidence of intestinal inflammation. In all groups, the gene expression was measured by RT-PCR.

Results

Patients with UC in remission had significantly higher IRGM gene expression in the colonic mucosa compared to active UC patients and normal controls (p=0.012 and p=0.013). The medical treatment response was associated with high gene expression of IRGM (p=0.001). Conversely, XBP1 and AGR2 gene expression was decreased in remission UC compared to active UC patients and controls (p=0.04 and p=0.04). The ORDML3 expression was decreased in patients with active UC compared to UC patients in remission and the normal control group (p=0.024 and p=0.0001). The ORDML3 levels were decreased in UC remission compared to the control group (p=0.003). The patients with active UC had significantly higher FCGR2A gene expression in colonic mucosa compared to remission UC patients and controls (p=0.035 and p=0.050). TNFRS14 gene expression was increased in patients with active UC compared with remission UC and controls (p=0.010 and p=0.000). The LAMP3 expression was increased in patients with active UC compared to UC patients in remission and the control group (p=0.020 and p=0.0005). The patients with active UC had significantly higher HSPA5 and UBE2L3 gene expression in colonic mucosa compared to controls (p=0.007, p=0.007). Conversely, CUL2 gene expression was decreased in active and remission UC groups compared to controls (p=0.000 and p=0.020). The UBD gene expression was decreased in patients with active UC compared to UC patients in remission and the control group (p=0.022 and p=0.015). Conversely, DOK3 gene expression was decreased in active and remission UC groups compared to controls (p=0.024 and p=0.010). The SNX20 expression was decreased in patients with active UC compared to UC patients in remission and the control group (p=0.000 and p=0.00001). The gene expression of LSP1, CTLA4 and HSP9 were higher in patients with active UC compared to remission UC (p=0.003, p=0.008 and p=0.036) and controls (p=0.001, p=0.010, p=0.035). CTLA4 gene was associated with histological activity index score (p=0.05 OR=14, 95% CI: 0.83–235).

Conclusion

This is the first transcriptomic analyses of a panel genes in the colonic mucosa from Mexican patients with UC.