P0066 Enhanced transcription of human endogenous retroviruses and downregulation of TRIM28 in patients with Crohn’s disease and ulcerative colitis

Abstract Background Human endogenous retroviruses (HERVs) represent 8% of the human genome. They originate from ancestral infections of germinal cells. HERVs are no longer infectious, but some retroviral sequences can be activated, and their aberrant expressions have been implicated in a number of diseases, including chronic inflammatory and autoimmune disorders. HERV transcription is regulated by TRIM28 and SETDB1, which are directly involved in epigenetic processes and in the modulation of the immune response. HERVs and TRIM28/SETDB1 expressions have not been investigated in patients affected by inflammatory bowel disease (IBD). Methods We assessed, through a PCR real-time Taqman amplification assay, the transcription levels of pol genes of HERV-H, -K, and -W families, of env genes of syncytin 1 (SYN1), SYN2, and HERV-W, as well as of TRIM28 and SETDB1 in whole blood of 48 patients with Crohn’s disease (CD), 20 with ulcerative colitis (UC) and in age-matched 104 healthy controls (HC). Results The transcriptional levels of HERV-H-pol (p=0.0003) and HERV-K-pol (p=0.001) were significantly higher in IBD patients as compared with HC, while no significant differences between the two groups were found for the remaining HERVs (Figure 1). The median mRNA levels of HERV-H-pol in CD was 1.53 (1.22–2.02), in UC was 1.56 (0.96–1.99), in HC was 1.24 (0.63–1.63); median HERV-K-pol in CD was 1.27 (1.00–1.76), in UC was 1.41 (0.99–1.85), in HC was 0.97 (0.71–1.34). The mRNA levels of TRIM28 were significantly downregulated in IBD patients (median mRNA levels of TRIM28 in CD = 0.73, 0.56–0.92, in UC = 0.76, 0.60–0.92, in HC = 1.01, 0.79–1.25, p < 0.001), while the SETDB1 levels were preserved (p = 0.95) (Figure 2). Conclusion Over-expressions of HERVs and impaired transcription of TRM28 in patients affected by CD or UC suggest that they might be main actors in the pathophysiology of IBD and open the way to innovative targeted interventions.