Modification of T-cell receptor Vβ repertoire in response to allergen stimulation in peanut allergy

Background: Peanut is one of the most common foods causing allergic reactions and is the most common cause of fatal and near-fatal food-related anaphylaxis. Little is known of the immunologic mechanisms that underlie peanut allergy. Objectives: In this study we examined clonality of the T-cell response (TCR) to peanut in MHC class II identical, peanut allergy–discordant sibling pairs. Methods: Four sibling pairs were investigated. The TCR repertoire was analyzed before and after in vitro stimulation of PBMCs with crude peanut or PHA, as control for general/nonspecific reactivity. Eighteen TCR-Vβ families were examined by flow cytometry. Where significant differences in incidence of particular TCR-Vβ families were observed, PCR familyspecific cDNA amplification and gene scanning were performed. Results: After stimulation with peanut, no selective expansion of any TCR-Vβ subpopulation was observed with flow cytometry, in either the peanut-allergic or nonallergic siblings, with the exception of 1 peanut-allergic subject who demonstrated a significant increase of TCR-Vβ11⁺ cells (0.3%-5.9% of the total CD3⁺ cells). However, gene scanning revealed predominant single-size PCR products for TCRBV11 in all peanut-allergic subjects after peanut stimulation. TCRBV11 polyclo-nality was observed in allergic and nonallergic subjects before peanut stimulation and in nonallergic subjects after peanut stimulation. In comparison, all subjects, before and after stimulation with peanut, showed polyclonality for TCRBV2.Conclusions: Our results argue for clonal or oligoclonal TCRs to crude peanut and indicate that changes in the TCRBV11 subpopulation are restricted to peanut-allergic subjects after stimulation with crude peanut allergen. (J Allergy Clin Immunol 2001;107:1089-94.)     

Immunochemical characterization of edible bird’s nest allergens

Background: We have previously described anaphylaxis induced by edible bird’s nest (BN) and demonstrated that this condition is IgE mediated. Objectives: This study aimed at describing the immunochemical properties of the BN allergens. Comparative studies between 3 commercially available sources (according to the country of origin) of BN were also made. Methods: Crude extracts of commercially available processed BN from Sarawak (Malaysia), Thailand, and Indonesia and fresh unprocessed BN from the caves of Sarawak were obtained by means of aqueous extraction. Specific IgE toward these sources were determined by using fluorescence allergosorbent tests (FASTs). Cross-reactivity studies between the 3 sources of commercially available processed BN were carried out by means of FAST inhibition. Immunochemical characterization by means of IgE immunoblot, periodate treatment, and heat stability studies were carried out on fresh unprocessed BN from Sarawak. Results: Serum from allergic patients showed differences in IgE binding to the 3 sources of commercially available BN, with the highest levels of specific IgE recorded with the Sarawak source (P < .0001). Of these, only the Sarawak and Thailand sources showed considerable cross-reactivity. Further work on the unprocessed fresh Sarawak source identified a putative 66-kd major allergen containing several isoforms. Periodate treatment resulted in loss of IgE binding. Despite a progressive decline in the molecular weights of allergens on SDS-PAGE with increasing periods of boiling, IgE binding, as assessed by means of FAST, was not affected. N-terminal sequence of the major putative allergen (66 kd) showed homology to a domain of an ovoinhibitor precursor in chicken (SWISS-PROT accession No. P10184). Conclusions: We have described the immunochemical properties of BN allergens. Edible BN from different sources are allergenically dissimilar. The putative major allergen is a 66-kd protein. (J Allergy Clin Immunol 2001;107:1082-8.)     

The effect of topically applied aspirin on localized circumscribed neurodermatitis

BACKGROUND: Lichen simplex chronicus is a troublesome intractable itchy dermatosis, which may persist despite intensive topical treatments. Recently it has been demonstrated that topical aspirin solution with dichloromethane has a significant antipruritic effect in an experimentally induced itch. OBJECTIVE: The aim of this double-blind, crossover placebo trial was to evaluate the efficacy of this solution in the treatment of lichen simplex chronicus. METHODS: Twenty-nine patients with lichen simplex chronicus of at least 3 months' duration that did not respond to topical corticosteroids were randomized in a double-blind fashion to receive aspirin/dichloromethane solution in treatment period 1 for 2 weeks followed by placebo in treatment period 2 or placebo followed by aspirin in period 2 with a crossover design after a 2-week washout. The patients rated the pruritus intensity before and during therapy with a visual analog scale; a blinded investigator performed photographic assessment. RESULTS: A significant therapeutic response was achieved in 11 (46%) of the patients who completed the study compared with 3 patients (12%) receiving placebo. Overall, aspirin-treated patients experienced an average decrease in the visual analog scale of 2.18 +/- 2.86 versus 0.69 +/- 2.31 of those receiving placebo. The difference between the 2 treatments for week 2 was significant (P =.03). CONCLUSION: The study suggests that topical aspirin/dichloromethane might be a practical treatment for lichen simplex chronicus.     

Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4 T lymphocytes and eosinophils in the nasal mucosa and increases the number of cells expressing messenger RNA for interferon-γ

BACKGROUND: Grass pollen injection immunotherapy is effective in patients with summer hay fever, although efficacy must be balanced against possible side effects. The mechanism of immunotherapy is unknown but may be related to its ability to inhibit allergen-induced late responses, which are known to be characterized by infiltration of T lymphocytes, eosinophils, and cells with messenger RNA for so-called T_H2-type cytokines (IL-4 and IL-5). OBJECTIVE: This study was designed to observe the effect of grass pollen immunotherapy on late nasal responses and associated cellular infiltration and cytokine mRNA expression. METHODS: We performed local nasal provocation with grass pollen (and a control challenge) in 28 patients after a 12-month double-blind, placebo-controlled trial of immunotherapy. Nasal biopsy specimens were obtained at 24 hours and processed for immunohistology and in situ hybridization studies. RESULTS: Grass pollen immunotherapy inhibited allergen-induced immediate (0 to 60 minutes) increases in sneezing (p < 0.02) and nasal blocking (p < 0.01) and late (0 to 24 hours) nasal symptoms (p < 0.05). Immunotherapy also inhibited the associated infiltration of the nasal mucosa by CD4⁺ T lymphocytes and total (major basic protein–containing) and “activated” (cationic protein–secreting) eosinophils (all p = 0.03). There was a significant (p = 0.04) increase in cells expressing mRNA for interferon-γ at 24 hours after allergen challenge, which correlated inversely with patients’ seasonal symptoms (r = -0.65, p < 0.05) and medication requirements (r = -0.75, p < 0.02) during the pollen season. CONCLUSION: The results suggest that successful grass pollen immunotherapy for summer hay fever may act by inhibiting allergen-induced T lymphocyte and eosinophil recruitment and eosinophil activation in the target organ, possibly through a mechanism involving protective local increases in T_H1-type cells. (J ALLERGY CLIN IMMUNOL 1996;97:1356-65.)