P073 Age dependent decrease in gut-homing CD4 lymphocytes

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Abstract

Background: α4β7 integrin is an important molecule in the regulation of leucocyte migration to intestinal tissue and a therapeutic target for treatment of inflammatory bowel disease (IBD). Although age-related changes in the composition of various lymphocyte subsets have been described, these have not been reported for gut homing (CD4+ α4β7+) lymphocytes. We postulate that paediatric IBD patients have a higher proportion of gut homing lymphocytes.

Methods: The expression of α4β7 was analysed in peripheral blood from 29 healthy controls (including 2 cord blood samples), 10 paediatric UC and 14 paediatric CD patients. Peripheral blood mononuclear cells were isolated using the Ficoll-density gradient centrifugation method, stained with labelled antibodies against CD3, CD4, α4-integrin and β7-integrin, and analysed using multi-coloured flow cytometry.

Results: Paediatric controls (healthy, non-IBD) had a significantly higher proportion of gut homing lymphocytes compared to the adult controls (p=0.008), Figure 1. There is a non-linear decline in gut homing lymphocytes with increasing age. The rate of decline is greater in the first decade and reaches a plateau in the fourth decade, Figure 2. When compared to healthy children of the same age, a large percentage of paediatric UC (60%) and CD (36%) patients had higher proportions of gut homing lymphocytes than expected, Figure 3.

Conclusions: Our study reports a higher proportion of gut homing lymphocytes in the paediatric population. This may have implications on treatment with Vedolizumab (anti-α4β7 monoclonal antibody). A clinical trial focusing on paediatric patients is needed to assess the efficacy of Vedolizumab in this population, and data from adult studies should not be extrapolated to the paediatric population.

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