B-FAHF-2 plus oral immunotherapy (OIT) is safer and more effective than OIT alone in a murine model of concurrent peanut/tree nut allergy.

BACKGROUND: Concurrent sensitization to peanut (PN) and tree nuts (TN), the most dangerous food allergies, is common. Current oral immunotherapy (OIT) is not fully satisfactory. OBJECTIVE: To determine whether the herbal formula B-FAHF-2 (BF2) ameliorates PN/TN OIT adverse reactions and enhances persistence of a tolerant state. METHODS: Concurrently sensitized PN-, walnut- (WN) and cashew (CSH)-allergic mice received 1-day PN/WN/CSH rush OIT plus 3 weeks of maintenance dosing, with or without 3 weeks prior and 3 weeks BF2 co-treatment. Anaphylactic symptom scores, core body temperatures, plasma histamine levels, basophil numbers, antigen-specific IgE, cytokine levels, and IL-4, INF-γ and Foxp3 gene promoter DNA methylation status, and their correlation with final challenge symptom scores were determined. RESULTS: BF2+OIT-treated mice experienced significantly fewer and less severe adverse reactions than OIT-only-treated mice (P<.01) during the 1-day rush OIT build-up dose phase. Both OIT-only and BF2+OIT mice showed significant desensitization (P<.01 and .001, respectively) at 1 week post-therapy challenge, being greater in BF2+OIT mice. All sham-treated and 91% of OIT-treated mice experienced anaphylaxis whereas only 21% of BF2+OIT-treated mice exhibited reactions during 5-6 weeks of dose escalation single PN and TN challenges. Greater and more persistent protection in BF2+OIT mice was associated with significantly lower plasma histamine and IgE levels, increased IFN-γ/IL-4 and IL-10/IL-4 ratios, DNA remethylation at the IL-4 promoter and demethylation at IFN-γ and Foxp3 promoters. Final challenge symptom scores were inversely correlated with IL-4 DNA methylation levels (P<.0002) and positively correlated with IFN-γ and Foxp3 gene promoter methylation levels (P<.0011) (P<.0165). CONCLUSIONS AND CLINICAL RELEVANCE: Combined BF2/OIT therapy was safer and produced longer post-treatment protection and more tolerance-prone immunological and epigenetic modifications than OIT alone. BF2/OIT may provide an additional OIT option for patients with concurrent PN/TN and other food allergies.

Induction of tolerance after establishment of peanut allergy by the food allergy herbal formula-2 is associated with up-regulation of interferon-gamma.

BACKGROUND: Peanut (PN)-anaphylaxis is potentially life threatening. We previously reported that a Chinese herbal medicine preparation, food allergy herbal formula-2 (FAHF-2), prevented peanut allergy (PNA) in mice when administered during sensitization. OBJECTIVE: To investigate whether FAHF-2 also can prevent anaphylactic reactions when administered to mice with established PNA and, if so, whether protection would persist after cessation of therapy. METHODS: C3H/HeJ mice sensitized and boosted over 8 weeks with a standard protocol known to establish PN hypersensitivity received seven weeks of FAHF-2 treatment or water as a sham treatment. Mice were subsequently challenged with PN at week 14 (1-day post-therapy) and week 18 (4-week post-therapy) to evaluate the efficacy and persistence of FAHF-2 treatment by assessing anaphylactic scores, core body temperatures and plasma histamine levels. Serum PN-specific antibody levels and cytokine profiles from splenocytes and mesenteric lymph node (MLN) cells were also determined. RESULTS: All sham-treated mice challenged at weeks 14 and 18 showed anaphylactic symptoms. In contrast, FAHF-2-treated mice showed no sign of anaphylactic reactions. PN-specific IgE levels in FAHF-2-treated mice also were reduced whereas IgG2a levels were increased. Furthermore, MLN cells from FAHF-2-treated mice produced markedly less IL-4 and IL-5, but more IFN-gamma, and contained increased numbers of IFN-gamma-producing CD8+ cells as compared with sham-treated mice. CONCLUSION: FAHF-2 treatment established PN tolerance in this model, which persisted for at least 4-week post-treatment. This result was associated with modulation of intestinal T helper type 1 cell (Th1) and Th2 cytokine production, and with increased numbers of mesenteric IFN-gamma-producing CD8+ cells.

Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model.

BACKGROUND: Peanut allergy is a major cause of fatal and near-fatal anaphylactic reactions to foods. There is no curative therapy for this condition. Traditional Chinese medicines have been reported to have antiallergic properties, which might be useful for treating peanut allergy. OBJECTIVE: The purpose of this study was to investigate the effects of a Chinese herbal formula, FAHF-1, on peanut anaphylactic reactions in a mouse model of peanut allergy. METHODS: Mice were sensitized with freshly ground whole peanut in the presence of cholera toxin and boosted 1 and 3 weeks later. FAHF-1 treatment was initiated 1 week later and continued for 7 weeks. After treatment, mice were challenged with peanut, and anaphylactic symptoms, body temperatures, and plasma histamine and IgE levels were measured. T-cell proliferative responses and cytokine production were also determined. RESULTS: FAHF-1 completely blocked peanut-induced anaphylactic symptoms and markedly reduced mast cell degranulation and histamine release. Peanut-specific serum IgE levels were significantly reduced by 2 weeks of treatment at the time of challenge, and they remained lower 4 weeks after discontinuation of treatment. FAHF-1 significantly reduced peanut-induced lymphocyte proliferation as well as IL-4, IL-5, and IL-13 synthesis but not IFN-gamma synthesis. No toxic effects on liver or kidney functions were observed, nor was there any overall immune suppression. CONCLUSION: FAHF-1 protected peanut-sensitized mice from anaphylactic reactions and significantly reversed established IgE-mediated peanut allergy. This suggests that FAHF-1 might prove valuable for the treatment of peanut allergy.

The chinese herbal medicine formula MSSM-002 suppresses allergic airway hyperreactivity and modulates TH1/TH2 responses in a murine model of allergic asthma.

BACKGROUND: Asthma is a major public health problem worldwide, and the morbidity and mortality of asthma have increased in the past two decades. The reputed efficacy, low cost, and relative absence of side effects of traditional Chinese medicines (TCMs) have led to increasing interest in the use of TCMs for the treatment of asthma in Western countries. However, there are few well-controlled scientific studies on the efficacy, safety, and mechanisms of action of TCMs used to treat asthma. OBJECTIVE: The goal of this study was to investigate the effects of the Chinese herbal medicine formula MSSM-002, derived from TCMs used to treat allergic asthma, on a well-characterized mouse model of allergic asthma. METHODS: Mice sensitized intraperitoneally and challenged intratracheally with conalbumin were treated with MSSM-002 24 hours after the first intratracheal challenge. Dexamethasone-treated, saline solution sham-treated, and naive mice served as controls. The effects of MSSM-002 on allergic airway hyperreactivity, inflammation, antigen-specific antibody production, lung histologic features, and cytokine profiles were evaluated. RESULTS: MSSM-002 treatment virtually eliminated airway hyperreactivity and markedly reduced the total number of cells and the percent eosinophils in bronchoalveolar lavage fluids compared with the sham-treated group. Lung histologic features showed that MSSM-002 reduced inflammation and mucus production. These effects were equivalent to the effects of dexamethasone, but in contrast to the overall immunosuppressive effects of dexamethasone MSSM-002 treatment decreased antigen-specific IgE, IL-4, IL-5, and IL-13 levels without suppressing IgG2a and IFN-gamma synthesis. CONCLUSION: MSSM-002 exhibits anti-airway hyperresponsiveness, anti-airway inflammation, and immunoregulatory effects on T(H)1/T(H)2 responses, which may be useful for treatment of allergic asthma.

Identification of unique peanut and soy allergens in sera adsorbed with cross-reacting antibodies.

BACKGROUND: Soybean and peanut are members of the legume family and share several common antigenic fractions. Patients allergic to one of these foods have serum IgE antibodies that immunologically cross-react with other legumes. Nevertheless, ingestion of other legumes generally does not induce an allergic reaction, suggesting that cross-reacting antibodies are not clinically relevant. OBJECTIVE: This study was designed to identify unique peanut or soybean antigenic fractions, with sera adsorbed to remove cross-reacting antibodies, thus resulting in sera with IgE antibodies unique to either soy or peanut. METHODS: Cross-reacting antibodies to soy were removed from the sera of two patients allergic to peanut and soy and three patients allergic to peanut by soy-affinity chromatography. Cross-reacting antibodies to peanut were adsorbed from the sera of a patient allergic to peanut and soy and a patient allergic to peanut by peanut-affinity chromatography. Adequate removal of cross-reacting antibodies was verified by ELISA after each adsorption step. Unadsorbed sera and sera adsorbed to remove cross-reacting antibodies (either to soy or to peanut) were assayed for specific IgE binding to peanut or soy immunoblots. RESULTS: Unique peanut-specific IgE antibodies (i.e., soy antibody-adsorbed) were found to bind to peanut fractions at 46, 29, 25, 19, 17, 14, and 5 kd on immunoblots of whole peanut protein. Similarly, unique soy-specific IgE (i.e., peanut antibody-adsorbed) were found to bind a fraction at 46 kd, and to a lesser extent, to a fraction at 21 kd on immunoblots of whole soy protein. The 73% reduction of IgE antibody binding to peanut by ELISA after adsorption of cross-reacting antibodies indicates extensive cross-reactivity between soy and peanut antigens. CONCLUSIONS: Antigen-affinity chromatography is an effective method for removal of cross-reacting antibodies. We identified IgE antibody binding (with sera where cross-reacting antibodies were removed) to several unique antigenic fractions of peanut and soy. Further studies will determine the clinical significance of these fractions in IgE-mediated food hypersensitivity reactions.

The role of allergens in atopic dermatitis.

AD is a disorder that affects up to 12% of the pediatric population. This disease is multifactorial and encompasses a wide array of etiologic factors. Strong evidence has existed in the literature over the past century for the role of inhalant and food allergies in the pathogenesis of AD. Much work is currently ongoing to delineate the role of individual cellular components, cytokines, and other mediators in the pathogenesis of AD. The answers to these questions, as well as a more comprehensive understanding of hereditary factors, will provide key information to our overall understanding of AD and our ability to treat patients with this disease more effectively in the future.

Anaphylactic reactions to a psyllium-containing cereal.

Historical data were obtained by questionnaire and telephone survey on 20 of 24 women with reported allergic reactions to a psyllium-containing cereal, Heartwise. Protein fractions from this new cereal, as well as from psyllium mucilloid and a psyllium-containing laxative, Metamucil, were extracted, quantitated, and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Patients' sera were collected, and specific IgE and IgG antibodies to these psyllium antigens were detected by immunoblotting techniques. Of the 20 women evaluated, all but six were nurses. Eighteen (90%) of the women had historical and/or laboratory evidence of atopy. Exposures included ingestion or dispensing of psyllium-containing products. Only three women denied prior exposure to psyllium. Symptoms developed shortly after small amounts of the cereal were ingested and most commonly included moderate to severe wheezing, throat and chest tightness, and urticaria. All the women required medical therapy, 11 (55%) in an emergency room. Specific IgE and IgG antibodies to various psyllium protein fractions were documented in all the subjects. It was concluded that individuals sensitized by occupational exposure to psyllium dust are at high risk for allergic reactions to ingested psyllium-containing products.

Cross-allergenicity in the legume botanical family in children with food hypersensitivity. II. Laboratory correlates.

Only two of 41 legume-allergic patients diagnosed by double-blind, placebo-controlled oral food challenge or "convincing history" of anaphylaxis had an IgE-mediated hypersensitivity reaction to more than one member of the legume family. However, extensive immunologic cross-reactivity was demonstrated among legume antigens on Immunoblot and Immunodot-blot analyses and prick skin tests. The proteins of six legumes (peanut, soybean, lima bean, pea, garbanzo bean, and green beans) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and probed with sera from six legume-allergic patients. Multiple IgE-binding bands were identified in each legume lane by the sera from each of these legume-allergic patients. In vitro cross-reactivity did not correlate with clinical hypersensitivity. All the legumes studied (except green bean) had a prominent band at 20 kd. Numerous proteins and protein subunits can be identified in each of the legumes (16 peanut, 21 soybean, 23 lima bean, 25 pea, 22 garbanzo bean, and 11 green bean protein bands) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it appears that legume-allergic patients' sera may recognize multiple similar fractions from each legume. A second in vitro test was performed in which the six legume extracts were bound directly onto nitrocellulose paper. These "legume" Immunodot blots were probed for specific IgE-binding activity with sera from 62 patients with positive legume prick skin tests. The legume Immunodot blots again demonstrated extensive clinically irrelevant cross-reactivity. However, this test may prove useful as a simple technique for screening food-specific IgE with minimal quantities of sera.

Cross-allergenicity in the legume botanical family in children with food hypersensitivity.

Sixty-nine patients with one or more positive prick skin tests to legumes (peanut, soybean, green bean, pea, and lima bean) were evaluated for food hypersensitivity with in-hospital oral food challenges. Of the 280 prick skin tests to legumes performed, 130 were positive. Forty-three positive food challenges occurred in 41 patients. The prevalence of legume allergy was not statistically different in those patients (N = 36) with two or more positive legume prick skin test (64% positive) compared to those patients (N = 33) with only one positive legume prick skin test (55% positive; p greater than 0.10). Even in this selected patient population, only two patients had symptomatic hypersensitivity to two legumes. Among patients with a positive prick skin test to peanut (N = 60), the mean wheal size was larger in patients with a positive versus a negative oral food challenge to peanut (p less than 0.001). Results of oral food challenges demonstrate that clinically important cross-reactivity to legumes in children is very rare. Clinical hypersensitivity to one legume does not warrant dietary elimination of all legumes. Results of prick skin tests should not be used to determine prolonged food restriction diets.

The role of "allergy" in atopic dermatitis.

Atopic dermatitis is a disorder that affects up to 4.3% of the pediatric population. Its etiology is unknown, but is probably multifactorial. Evidence has been presented to implicate a role for "allergy" in the pathogenesis of AD. Disregarding the myriad of clinical reports, there is sufficient data in the literature to suggest an etiologic role for inhalants (pollen, mold, and dust mite) and foods in some patients with AD. Definitive studies have demonstrated that both inhalant and food antigens can be absorbed rapidly and transported to the skin, where sensitized mast cells can be activated. Controlled challenges have demonstrated skin reactions following exposure to inhalant and food antigens in sensitive subjects. Activiation of mast cells and/or basophils has been shown following oral food challenges in sensitized children with AD. Although sufficient evidence is now available to implicate "allergy" as an etiologic factor in atopic dermatitis, the link between mast cell activation and the development of eczematous skin changes remains to be clearly defined.