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OP015. Gut homing markers in perianal Crohn's fistulae

N.A. Yassin1, A. Askari1, Y.H. Siaw1, E. Mann2, D. Bernardo2, R.K.S. Phillips1, S. Knight2, H. Al-Hassi2, A.L. Hart1, 1St Mark's Hospital, and Academic Institute, London, United Kingdom, 2Imperial College London, Antigen Presentation Research Group, London, United Kingdom

Background

Microbiological, genetic and immunological factors have been implicated in the aetiology of Crohn's disease (CD). The aetiology of perianal Crohn's fistulae remains unclear and the disease a challenge to treat. Dendritic cells are antigen presenting cells that play a role in the immunopathogenesis of CD and express tissue-specific homing markers. We have recently shown that the expression of gut homing markers (β7 integrin) on dendritic cells to be significantly higher in Crohn's compared with idiopathic fistulae. The β7 chain associates with the α4 subunit to form the α4 β7 integrin, but it also combines with the α E chain to form the α E β7 integrin. We aimed to determine specific β7 gut homing marker expression on dendritic cells from the fistula tracts of patients with perianal CD.

Methods

Fresh biopsies were taken from 35 Crohn's and 25 idiopathic fistula patients. Dendritic cells were identified as HLA-DR positive and lineage (CD3, CD14, CD16, CD19, CD34 and CD56) negative, and were characterized by flow cytometry. The expression of CLA and αE β7-integrin was tested in both groups. Additional biopsies were taken for the second study from 17 Crohn's anal fistula tracks. The expression of the gut homing markers (β7 integrin and α E β7) was tested.

Results

The male to female ratio for the idiopathic group was 18:7, and 21:14 for the Crohn's group. Of the idiopathic group, 14% were smokers as compared with 18.4% of the Crohn's group. A diverting stoma was present in 15.8% of the Crohn's group at the time of taking biopsies as compared with 5% of the idiopathic group.

Percentage positive expression of β7 integrin on DC was significantly higher in Crohn's compared with idiopathic fistulae (p = 0.002). In the Crohn's subgroup, β 7-integrin (median 44, range 0–75) was significantly higher (p = 0.003) than α E β7 (median 4, range 0–65). This implies that the positive expression of β7 integrin in Crohn's is due to the α4 β7 molecule. Positive correlation was found between the duration of perianal disease and increased β7 levels (r = 0.473, p = 0.005). However, there was no correlation between all the other factors including the use of infliximab alone or in combination with thiopurines with β7 expression on DC.

Conclusion

Increased expression of β7 on dendritic cells of Crohn's perianal fistulae implies a dysregulated immune response which could be directing T-cells to the gut. Significantly more expression of the β7 integrin as compared with the α E β7 gut homing marker, implies this significance to be due to the α4 β7 antibody. Anti-α4 β7 therapies may aid healing when applied to perianal Crohn's fistulae.