Randomized controlled trial of primary prevention of atopy using house dust mite oral immunotherapy in early childhood

The epidemic proportion of atopic diseases in the last 30 years has resulted in major health and economic effects. Atopy is believed to be due to a genetic propensity to produce IgE antibodies in response to an allergen; such propensity is due to an imbalance between various lymphocyte subsets,TH1, TH2 and T regulatory (Treg) cells in particular. In the absence of early intervention, children born with atopic diathesis are likely to develop allergic disease. Zolkipli et al. report the results of a house dust mite allergy prevention study conducted in infants (J Allergy Clin Immunol 2015; 136(6): 1541-1547). 

Overcoming maturation deficiencies in the developing immune system and countering T_H2 bias requires a very early strong and adequate immune stimulation. In the first 18 months of life, the gut is the primary site of Treg cells stimulation in response to antigens, suggesting oral exposure is likely the most effective in inducing tolerance. The authors hypothesized that exposure to a ubiquitous allergen, such as house dust mite (HDM), would result in both HDM-allergen-specific and a more generalized desensitization effect preventing the atopic march. One hundred eleven infants less than one year of age who had two or more first-degree relatives with allergic disease received an oral administration of HDM extract twice daily for 12 months.

The authors found that HDM-allergen extract induced a significant reduction in sensitization to any common allergen as compared to placebo. There was, interestingly, no significant difference in the cumulative proportion of infants who developed HDM-specific sensitization between the active and placebo groups, nor did HDM-allergen extract impact the number who developed eczema, wheeze, or food allergy. The intervention was well-tolerated, with no differences between the two groups in relevant adverse events.

This early proof-of-concept study points to a feasible, safe, and effective preventive measure. High-dose HDM-allergen extract appears to exert a prophylactic effect on the development of atopy, as defined by skin prick test response to any common allergen. Preventive reduction in allergen sensitization in early childhood may translate into a reduction of asthma, eczema, rhinoconjunctivitis, and food allergy as children at risk for these diseases grow up.