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* = Presenting author

P073 Age dependent decrease in gut-homing CD4 lymphocytes

Oh S.*1, Lee C.H.2, Hsu P.3, Hu M.4, Nanan B.4, Gaskin K.2, Leong R.5, Nanan R.4

1University of New South Wales, Kensington, Australia 2James Fairfax Institute of Paediatric Clinical Nutrition, University of Sydney, Sydney, Australia 3The Children's Hospital at Westmead, Department of Allergy and Immunology, Westmead, Australia 4University of Sydney, Nepean Clinical School, Sydney, Australia 5Concord and Bankstown Hospitals, Department of Gastroenterology, Sydney, Australia

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.

Figure 1. Proportion of gut homing lymphocytes in adult and paediatric controls.

Figure 2. Age-dependent decline in gut homing lymphocytes.

Figure 3. Proportion of gut homing lymphocytes in paediatric UC (A) and CD (B) patients compared to their healthy counterparts.

Conclusion

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.