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Chuang, S.1; Hayes, P.1; Haddad, M.1; MacDonald, T. T.2; Fell, J. M.1
1Paediatric Gastroenterology, Chelsea and Westminster Hospital, London, 2Div Infection, Inflammation and Repair, University, Southampton, United Kingdom
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Introduction: AC is a well recognised cause of rectal bleeding in infancy. Dietary antigens have been clinically implicated, in particular, cow’s milk protein (CMP). The underlying immune mechanism remains elusive. The aim of the study is to characterise the systemic and gut mucosal Th1/ Th2 cytokine profile in infants with allergic colitis and, to correlate the clinical CMP sensitivity with in vitro response.
Methods: 9 AC infants (6/9 breast fed, onset 2 days-7 months) and 11 (non-inflamed) normal infant controls were studied. AC infants were classified as CMP sensitive (CMP+ve; n=6) or insensitive (CMP-ve; n=3) according to their clinical responses to dietary manipulations +/− double blind challenge. 8/9 AC infants underwent rectal biopsy. Cytokine profile, IFNg, IL-4 and IL-5, was enumerated by ELISPOT assay for peripheral blood (PBMC) and lamina propria (LPMC) mononuclear cells, at rest and following stimulation with mitogens (PHA, ConA) and CMP (beta-lactoglobulin, BLG and alpha-casein).
Results: PBMC: All controls and 7/9 AC infants showed no detectable spontaneous cytokine secretion. Mitogen stimulation produced a marked increase in cytokine production in AC infants, IFNg> IL-4 or IL-5, compared to controls. LPMC from both controls and AC infants also showed no resting cytokine activation. ConA elicited a significant mucosal response in AC infants (IFNg: p=0.01 and IL-4: p=0.01) but none in controls. In vitro CMP stimulation had no effect on PBMC or LPMC in controls and CMP-ve AC infants. In contrast, 3/6 CMP+ve AC infants had increased PBMC response to BLG and/or casein, albeit in no polarised Th1 or Th2 pattern. LPMC from 2/6 CMP+ve AC infants were milk antigen reactive (predominant BLG induced IL-5 secretion).
Conclusion: This is the first study that has attempted to correlate the in vivo with in vitro dietary antigen response in allergic colitis. Results following PHA/ConA stimulation illustrate Th1/Th2 immune activation in AC. In vitro CMP sensitisation could only be demonstrated in a minority of AC infants although all the in vitro responders had clinical evidence of CMP sensitisation. The differences may reflect limitations in assay sensitivity and the complexity of mucosal immune regulatory network.
© 2004 Lippincott Williams & Wilkins, Inc.
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