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Summary: Background: Oral immunotherapy (OIT) successfully desensitizes patients with food allergies, but the immune mechanisms mediating its efficacy remain obscure. Objectives: We tested the hypothesis that allergen‐specific regulatory T (Treg) cell function is impaired in food allergy and is restored by anti‐IgE antibody (omalizumab)‐supplemented OIT. Methods: Peanut‐specific T effector (Teff) and Treg cell proliferative responses, activation markers and cytokine expression were analysed by flow cytometry in 13 peanut‐allergic subjects before the start of omalizumab‐supplemented OIT and periodically in some subjects thereafter for up to 2 years. Peripheral blood regulatory T cells (Treg cells) were analysed for their peanut‐specific suppressor function before and at 1 year following OIT. This study was registered on ClinicalTrials.gov (NCT01290913). Results: Proliferation of allergen‐specific Teff and Treg cells precipitously declined following the initiation of omalizumab therapy prior to OIT, followed by partial recovery after the initiation of OIT. At baseline, peanut‐specific Treg cells exhibited a Th2 cell‐like phenotype, characterized by increased IL‐4 expression, which progressively reversed upon OIT. Peanut‐specific Treg cell suppressor activity was absent at the start of omalizumab/OIT therapy but became robust following OIT. Absent peanut‐specific Treg cell function could also be recovered by the acute blockade of IL‐4/IL‐4R receptor signalling in Treg cells, which inhibited their IL‐4 production. Conclusions and Clinical Relevance: OIT supplemented by omalizumab promotes allergen desensitization through an initial omalizumab‐dependent step that acutely depletes allergen‐reactive T cells, followed by an increase in allergen‐specific Treg cell activity due to the reversal of their Th2 cell‐like programme. Improved Treg cell function may be a key mechanism by which OIT ameliorates food allergy. [ABSTRACT FROM AUTHOR]

Presents a case study of a nine-year-old boy with a primary immunodeficiency characterized by severe recurrent infections. He had autoimmune hemolytic anemia, bronchiectasis, and Hodgkin's disease. Study details; Results; Conclusions.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive disease of unknown etiology characterized by metaphyseal dysostosis, unpigmented hair, and defective cellular immunity. We studied peripheral blood mononuclear cells (PBMC) of a boy with CHH and combined immunodeficiency in an attempt to characterize further the immune defect in this disease. Stimulation of his PBMC with mitogens was associated with severely depressed IL-2 and interferon-gamma (IFN-γ) synthesis and IL-2 receptor a-chain (IL-2Rα) expression and resulted in poor lymphocyte proliferation that was only modestly upregulated by the addition of recombinant IL-2 (rIL-2). The defective proliferation and lymphokine synthesis were not corrected by the addition of phorbol myristate acetate (PMA) and ionomycin, agents that bypass receptor-mediated signalling, indicative of a distal abnormality. Importantly, the levels of mRNA encoding c-myc, IL-2Rα, IL-2 and IFN-γ were markedly decreased in patient lymphocytes stimulated with PMA + ionomycin as compared to control lymphocytes The defect in the expression of these early activation genes was selective in that induction by mitogens of mRNA encoding other early activation gene products such as c-fos and c-jun was not impaired. These results suggest that the underlying defect in this patient and perhaps others with CHH may be an abnormality in a component of intracellular signalling pathways or in a trans-acting factor which regulates the expression of a selected number of early activation genes. [ABSTRACT FROM AUTHOR]