E. Hoyte

Immunology : hepatitis A virus link to atopic disease

Atopic diseases, including asthma, allergic rhinitis and atopic dermatitis, are caused by both environmental and genetic factors. Here we show that infection by hepatitis A virus (HAV) may protect individuals from atopy if they carry a particular variant of the gene that encodes TIM-1 (also known as HAVcr-1) — the cell-surface receptor used by HAV to infect human cells. Exposure to HAV is associated with poor hygiene, large family size and attendance at day-care centres, all factors that are also inversely associated with atopy. Our discovery indicates that interaction between HAV and TIM-1 genotype may contribute to the aetiology of atopic diseases, and provides a mechanism to account for the hygiene hypothesis.

Changes in antigen-specific T cell number and function during oral desensitization in cow’s milk allergy enabled with omalizumab

Food allergy is a major public health problem, for which there is no effective treatment. We examined the immunological changes that occurred in a group of children with significant cows milk allergy undergoing a novel and rapid high-dose oral desensitization protocol enabled by treatment with omalizumab (anti-immunoglobulin (Ig)E monoclonal antibodies). Within a week of treatment, the CD4+ T-cell response to milk was nearly eliminated, suggesting anergy in, or deletion of, milk-specific CD4+ T cells. Over the following 3 months while the subjects remained on high doses of daily oral milk, the CD4+ T-cell response returned, characterized by a shift from interleukin-4 to interferon-γ production. Desensitization was also associated with reduction in milk-specific IgE and a 15-fold increase in milk-specific IgG4. These studies suggest that high-dose oral allergen desensitization may be associated with deletion of allergen-specific T cells, without the apparent development of allergen-specific Foxp3+ regulatory T cells.

Immunologic Effects of Omalizumab in Children with Severe Refractory Atopic Dermatitis: A Randomized, Placebo-Controlled Clinical Trial

Background: Severe refractory atopic dermatitis (AD) is a chronic, debilitating condition that is associated with elevated serum immunoglobulin E (IgE) levels. Thymic stromal lymphopoietin (TSLP), thymus and activation-regulated chemokine (TARC) and OX40 ligand (OX40L) are important immunologic factors involved in the pathogenesis of AD. Omalizumab, an anti-IgE antibody indicated for use in allergic asthma, is implicated in regulating allergen presentation by dendritic cells and the T cell response during the effector phases of allergic disease. We investigated if anti-IgE therapy modulates the allergen-specific responses mediated by the TSLP pathway in young patients with severe refractory AD. Methods: This was a randomized, double-blind, placebo-controlled study of 8 patients between the ages of 4 and 22 years (mean = 11.6 years) with severe refractory AD (clinical trials.gov NCT01678092). Serum IgE ranged from 218 to 1,890 (mean = 1,068 IU/ml). Subjects received omalizumab (n = 4) or placebo (n = 4) every 2-4 weeks over 24 weeks using a regimen extrapolated from the package insert. TSLP, TARC, OX40L and other cytokines involved in AD were measured by using cytometric bead arrays. Results: All patients receiving omalizumab had strikingly decreased levels of TSLP, OX40L, TARC (involved in Th2 polarization) and interleukin (IL)-9 compared to placebo. In addition, there was a marked increase in IL-10, a tolerogenic cytokine, in the omalizumab-treated group. Patients on anti-IgE therapy had an improvement in clinical outcomes as measured by the SCORAD system; however, these effects were comparable to improvements in the control group. Conclusions: Anti-IgE therapy with omalizumab decreases levels of cytokines that are involved in Th2 polarization and allergic inflammation, including TSLP, TARC and OX40L.