Peanut allergy: recent advances

A review of: Leung DYM, Sampson HA, Yunginger JW, _et al._, for the TNX-901 Peanut Allergy Study Group 2003 Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med

348:986–993; and Lack G, Fox D, Northstone K, Golding J, for the Avon Longitudinal Study of Parents and Children Study Team 2003 Factors associated with the development of peanut allergy in

childhood. N Engl J Med 348:977–985 The number of infants, children, and adolescents who are at risk for systemic anaphylaxis is increasing; in one geographic area, 1.44% of the pediatric

population has had epinephrine dispensed for first-aid, out-of-hospital treatment (1). In young patients, peanut allergy is the most common food trigger of anaphylaxis, and it is also the

most common overall trigger, accounting for up to 50% of all anaphylaxis episodes in this age group (2). Recent articles on peanut allergy in _The New England Journal of Medicine_ give

reason for cautious optimism about prevention of peanut-induced allergic _reactions_ by injecting the anti-IgE antibody TNX-901 (3), and about the possibility of prevention of

_sensitization_ to peanut by avoidance of newly identified risk factors for peanut allergy (4). Leung et al explored the novel approach of injecting a humanized IgG1 monoclonal anti-IgE

antibody, TNX-901, in a Phase II, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study lasting 3–4 months. They investigated 81 patients age 13-59 years with a total

serum IgE level ranging from 11-1017 IU/mL (mean 273 IU/mL), positive epicutaneous test to peanut, and positive double-blind, placebo-controlled oral challenge to peanut flour (mean

baseline threshold sensitivity of 331 mg (range 1–2000), equivalent to 1/2–1 peanut). TNX-901 150, 300, or 450 mg, or placebo was injected subcutaneously every 4 weeks for a total of four

doses. TNX-901 injections led to substantial reduction in serum free IgE levels in all the active treatment groups. Approximately 3 weeks after the last injection, compared with unchanged

tolerance in the individuals receiving placebo, those receiving TNX-901 450 mg had increased tolerance to peanut flour (_p_ < 0.001), expressed as the mean threshold of sensitivity of

2805 mg (approximately 8–9 peanuts), and there was a trend for a dose response to TNX-901 (_p_ < 0.001). Some allergen-specific IgE remained. Most individuals receiving TNX-901 developed

mild local reactions at the injection sites. Systemic allergic reactions to the peanut flour challenges were not completely prevented and required termination of the challenge and treatment

with oral charcoal, epinephrine, antihistamines, and corticosteroids, as appropriate. No individual developed anti-TNX-901 antibodies. Anti-IgE antibodies work by binding with high affinity

to an epitope in the CH3 domain of IgE and forming small, discrete complexes with free IgE in the serum, thus masking the region responsible for binding to the Fcε receptor (IgE receptor I)

on mast cells and basophils (3). Due to the fact that anti-IgE antibodies do not interact with receptor-bound IgE on these cells to trigger the release of histamine, tryptase, and other

mediators, they do not trigger anaphylaxis. Anti-IgE antibodies also reduce the number of IgE receptors on basophils and bind to the constitutive IgE expressed by differentiated B cells, the

precursors of IgE-secreting plasma cells. They do not bind to structurally unrelated IgE-binding receptors (IgE receptor II) expressed on lymphocytes and monocytes. Additional anti-IgE

antibody studies are needed in children less than 13 years of age, and in patients with more severe peanut allergy who cannot tolerate _any_ ingestion of peanut before treatment. In

individuals with greatly elevated total serum IgE levels (>1000 IU/mL) and those with large body mass, it might be difficult to inject an adequate anti-IgE antibody dose. Injections might

be needed indefinitely in many peanut-allergic patients, since sensitization to peanut is rarely lost (5). Although IgE appears to be involved in most humans with anaphylaxis, the

possibility of non-IgE-dependent anaphylaxis occurring in some individuals, as documented in other mammalian species (6), cannot be ruled out. Moreover, subacute or chronic food allergy

symptoms are generally mediated by T cells rather than by IgE (5). Most allergic individuals have more than one disease phenotype; therefore, a potential advantage of anti-IgE antibody over

currently available treatments is that it is not specific for a particular allergy such as peanut allergy, or for a particular allergic disorder such as anaphylaxis. Indeed, the monoclonal

anti-IgE antibody omalizumab (Xolair®) reduces asthma and allergic rhinitis symptoms significantly (7, 8). In another study published in the same issue of _The New England Journal of

Medicine_, Lack et al identified previously unreported risk factors for peanut allergy in a geographically defined cohort of 13,971 preschool children, 23 of whom had peanut allergy

confirmed by double-blind peanut challenge (4). Case children and controls were not matched. A significant independent relationship of peanut allergy was found with: application of skin

creams containing peanut oil to inflamed skin (Odds Ratio (OR), 6.8; 95% Confidence Interval (CI), 1.4–32.9); atopic dermatitis (OR, 2.6; 95% CI, 1.4–5.0); oozing, crusted rash (OR, 5.2; 95%

CI, 2.7–10.2); and intake of soy milk or soy formula (OR, 2.6; 95% CI, 1.3–5.2), perhaps through cross-sensitization to common epitopes in peanut and soy. There was no evidence that

sensitization to peanut was attributable to the maternal diet, either before birth or by transmission of maternally ingested peanut allergens through breast milk. IgE synthesis and

production of pro-inflammatory cytokines are favored by exposure to extremely low concentrations of allergens (9). If these risk factors involving exposure to minute amounts of peanut are

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permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Simons, F. Peanut Allergy: Recent Advances. _Pediatr Res_ 54, 291–292 (2003). https://doi.org/10.1203/01.PDR.0000088364.16983.E1 Download

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