In children with cow's milk allergy, 1-kestose affects the gut microbiota and reaction threshold.

BACKGROUND: Interventions targeting the gut microbiota for treating food allergy (FA) have been gaining much attention. Although several studies have examined the effects of probiotics, few have verified the effects of prebiotic intervention on FA in humans. METHODS: We conducted a preliminary open-label, parallel-group comparison trial in children diagnosed with severe cow's milk allergy (CMA) who were instructed to ingest baked milk (BM; bread or cookies) daily. The subjects either received or did not receive the prebiotic 1-kestose (kestose) daily for 6 months. CMA symptoms and the threshold dose for milk protein were evaluated by oral food challenge with heated milk or BM. Blood and fecal samples were also collected for investigations of the antigen-specific immunoglobulin (Ig) E levels and microbiota composition. RESULTS: Kestose treatment significantly increased the threshold dose for milk protein, and decreased the milk- and casein-specific IgE levels in serum. In those treated with kestose, the abundance of Fusicatenibacter spp. significantly increased in the feces, and a significant inverse correlation was seen between the abundance of Fusicatenibacter spp. and the milk- and casein-specific IgE levels. CONCLUSION: Kestose treatment induced some tolerance to milk protein via changes in the gut microbiota composition in children with FA. IMPACT: A 6-month treatment with the prebiotic kestose increased the threshold dose for milk protein, and decreased the serum levels of milk- and casein-specific IgE in children diagnosed with cow's milk allergy. The kestose treatment increased the abundance of Fusicatenibacter spp. in the gut, which was inversely correlated with the antigen-specific IgE levels. This is the first study to demonstrate that a prebiotic intervention induced some tolerance to an allergen in children with food allergy.

Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study.

BACKGROUND: Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. METHODS: A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. RESULTS: The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. CONCLUSIONS: Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT. TRIAL REGISTRATION: UMIN000009373, Multicenter Oral Immunotherapy for Hen's Egg, Cow's Milk, and Wheat-Allergic Children at Outpatient Clinic.

Changes in the characteristics of patients with latex allergy from 1999 to 2014.

OBJECTIVES: We conducted a multicenter study using the same questionnaire in 1999 and 2014 to investigate changes in the characteristics of patients with latex allergy. METHODS: We mailed questionnaires on latex allergy to hospitals in Japan that were members of the Japanese Latex Allergy Society. RESULTS: We compared the 25 responses received in 2014 and the 81 responses received in 1999. With regard to the age distribution, the number of patients with latex allergy in their 20s declined significantly from 1999 to 2014 (P=0.004). The largest proportion of latex allergy cases was observed among those aged <10 years. The incidence of cases caused by medical rubber gloves decreased significantly (P=0.004). Moreover, latex-fruit syndrome increased from 15% to 40% (P=0.006). CONCLUSIONS: Our findings indicate that the frequency of occurrence of latex allergy in people in their 20s decreased from 1999 to 2014. The largest proportion of latex allergy cases was observed among those aged <10 years. Future measures to protect children are required.

Age-associated effect of kestose on Faecalibacterium prausnitzii and symptoms in the atopic dermatitis infants.

BACKGROUND: Although Faecalibacterium prausnitzii is a major bacterium in the intestine of adults, which is known to have anti-inflammatory effects, the development in infants or the response to prebiotics remains unclear. METHODS: The counts of F. prausnitzii in the feces were examined by real-time polymerase chain reaction (PCR). Fecal samples were obtained from 65 atopic dermatitis (AD) infants who participated in a randomized controlled clinical trial to investigate the therapeutic effect of kestose, the smallest fructooligosaccharide. RESULTS: Although the F. prausnitzii count was undetectable level in most 0- to 1-y-old infants, the count reached a level comparable to that in adults in 2- to 5-y-old infants. The bacterial number increased about 10-fold by oral administration of kestose every day for 12 wk in the younger infants, but not so much in the older infants. This bacterial increase was significantly correlated with an improvement in the AD symptoms in the older infants. CONCLUSION: The F. prausnitzii population in the intestine reaches a level comparable to that in adult at approximately 2 y of age. Kestose efficiently stimulates the growth of this bacterium in the intestine, which might lead to an improvement in AD symptoms in infants.

[A case of food-dependent exercise-induced anaphylaxis caused by ingestion of orange].

The patient was a 10-year-old girl who presented with a history of anaphylactic episodes on three occasions, that developed in association with exercise after she ate citrus fruit. She underwent tolerance tests, as food-dependent exercise-induced anaphylaxis (FDEIA) induced by citrus fruit was suspected. The result of the test for the combination of intake of oranges and exercise was negative. The patient presented with swollen eyelid and wheezing following combined intake of orange and aspirin, based on which she was diagnosed as having FDEIA. Many patients developing an allergic reaction to fruit are diagnosed as having oral allergy syndrome (OAS), and only few cases of FDEIA are reported. Immunoblot tests revealed antigens of 9 kDa, 39 kDa and 53 kDa in this patient, and an inhibition study with oranges revealed that the 39 kDa and 53 kDa antigens were probably antigen-specific allergens. Although the studied patient showed a strongly positive result for IgE antibodies specifically directed at cedar pollen, no common antigenicity with cedar pollen could be recognized. The final diagnosis was a type of FDEIA caused by 39 kDa and 53 kDa proteins, which are different from antigens previously identified in patients with citrus fruits allergy. It should be the first report of such a case.

The use of complementary and alternative medicine by pediatric food-allergic patients in Japan.

BACKGROUND: In developed countries, increasing food allergy prevalence and concern regarding food allergies have been reported. Although the use of complementary and alternative medicine (CAM) for the treatment of allergic diseases has increased in some Western countries, the actual proportion and patterns of CAM use for pediatric food allergies in Japan are still unknown. METHODS: Fourteen allergy centers in Japan participated in the study using a questionnaire survey regarding the use of CAM by pediatric patients. A diagnosis of food allergy was made at each hospital by pediatric allergists. RESULTS: Surveys were completed by parents/guardians, and data were collected for a total of 962 pediatric food-allergic patients. Overall, 8.4% of the participants used CAM to treat a food allergy. The major CAM therapies used were herbal teas (22.2%), including several Japanese herbal teas, Chinese herbal medicine (18.5%) and lactic acid bacteria (16%). Among the participants using CAM to treat food allergy, 13.6% thought that the CAM being used was very effective, while 11.1% of participants thought that CAM caused some type of side effect. CONCLUSIONS: Our study is the first large-scale national survey regarding the use of CAM in pediatric patients with food allergies in Japan. Unlike in the USA, which has a higher rate of CAM use (17%), approximately 8.4% of food-allergic patients used CAM in Japan. Interestingly, the major types of CAM used in Japan differed from those used in the USA. Cultural differences and food customs may affect the use of CAM.

The Relationship between Symptom Flare of Atopic Dermatitis and Airborne Japanese Cedar and Cypress Pollen Counts: A Self-Scoring Diary Study.

Background. With an increase in Japanese cedar and cypress (JC) pollinosis, the relationship between JC pollen and atopic dermatitis (AD) has been studied. Some reports suggest that JC pollen can be one exacerbating factor for AD, but there has been no report that discusses JC pollen counts relating to AD symptom flare although actual airborne JC pollen counts can widely fluctuate throughout the pollen season. Objective. The relationship between symptom flare of AD and airborne JC pollen counts was examined. Methods. We monitored JC pollen counts in real time and divided the counts into low and high level. We then analyzed self-scored "itch intensity" recorded by 14 AD patients through a self-scoring diary. Results. Among the 14 patients, 7 had significantly higher itch intensity while the pollen counts were high. Conclusion. Even during the pollen season, actual airborne pollen counts can widely fluctuate. Our study suggested that symptom flare of AD could be influenced by the actual pollen counts.

The usefulness of combined measurements of squamous cell carcinoma antigens 1 and 2 in diagnosing atopic dermatitis.

BACKGROUND: The squamous cell carcinoma antigen (SCCA) is widely used as a serological biomarker for various cancers. There are two known SCCA molecules, SCCA1 and SCCA2. We previously found that interleukin-4 or interleukin-13, two related Th2-type cytokines that play an important role in allergic diseases, induce expression of SCCA1 and SCCA2. In this study, we examined whether combined measurements of SCCA1 and SCCA2 are useful for diagnosing atopic dermatitis (AD). METHODS: We established new enzyme-linked immunosorbent assays (ELISAs) to specifically detect SCCA1 or SCCA2. We applied serum samples from AD patients with food allergies and from cervical cancer patients to these ELISAs. We performed receiver operating characteristic analyses to diagnose AD and to distinguish AD from cervical cancer. RESULTS: Serum concentrations of both SCCA1 and SCCA2 were elevated in AD patients. The serum concentrations of SCCA1 and SCCA2 positively correlated with the clinical severity of AD, showing high specificity (0.86-0.88) and sensitivity (0.86) against control donors. The serum concentrations of SCCA1 and SCCA2 were elevated in cervical cancer patients; however, the SCCA2/SCCA1 ratios clearly distinguished AD patients from cervical cancer patients with high specificity (0.87) and sensitivity (0.87). Expression of SCCA2 was predominant in AD patients, whereas cervical cancer patients showed a predominance of SCCA1. CONCLUSIONS: Combined measurements of SCCA1 and SCCA2 are very useful in estimating the severity of allergic diseases, making it possible to distinguish allergic diseases from cancers.

Clinical utility of IgE antibodies to ω-5 gliadin in the diagnosis of wheat allergy: a pediatric multicenter challenge study.

BACKGROUND: There are contradictory results regarding the clinical usefulness of the determination of IgE antibodies to ω-5 gliadin in children with a suspicion of wheat allergy (WA). METHODS: The study comprised 311 children and young adults with suspected wheat intolerance treated at three separate pediatric clinics and, with the exception of 25, were found to be positive in specific IgE antibody determinations to wheat. Their ages ranged from 6 months to 20.4 years (median age, 2.3 years). Possible relationships between IgE antibodies to ω-5 gliadin and a physician's diagnosis of WA and challenge symptoms were studied. RESULTS: The mean concentration of IgE antibodies to ω-5 gliadin was 1.2 kU(A)/l in WA patients and <0.35 kU(A)/l in patients without WA (p < 0.0001). Seventy-two percent of the WA patients had positive ω-5 gliadin levels and 75% of the patients without WA had negative levels. Logistic regression showed a significant relationship between the probability of WA and the concentration of IgE antibodies to ω-5-gliadin with a 2.6-fold (95% CI: 2.0-3.3) increased risk. Age was an important factor to consider as the risk of WA increased 5.4-fold (95% CI: 1.4-21) for children ≤1 year of age and 2.5-fold (95% CI: 2.0-3.2) for children >1 year of age with increasing levels of IgE. CONCLUSION: Detection of IgE to ω-5 gliadin seems to be associated with responsiveness to the challenge test and is particularly useful in infants with a suspicion of WA.

Usefulness of specific IgE antibodies to ω-5 gliadin in the diagnosis and follow-up of Japanese children with wheat allergy.

BACKGROUND: Gliadins have been implicated in IgE-mediated allergy to ingested wheat. ω-5 gliadin seems to be a clinically relevant allergen component in children with immediate wheat allergy (WA), but contradictory results have been published. OBJECTIVES: To investigate whether specific IgE (sIgE) antibodies to recombinant ω-5 gliadin could be used as a marker for oral wheat challenge outcome in wheat-sensitized children and to study whether measurements of sIgE to ω-5 gliadin are useful in monitoring children with WA to assess whether the allergy is outgrown or persistent. METHODS: Eighty-eight serum samples from children sensitized to wheat were collected consecutively. sIgE to ω-5 gliadin was related to a physician's diagnosis of WA. RESULTS: Sixty-seven of 88 children sensitized to wheat were diagnosed as having WA. The geometric mean concentrations of sIgE to ω-5 gliadin were 2.04 kU(A)/L (range, <0.35-100 kU(A)/L) in children with WA and 0.40 kU(A)/L (range, <0.35-1.8 kU(A)/L) in children without WA. At follow-up, after being on a wheat-free diet for approximately 2 years, the sIgE titers to ω-5 gliadin were below 0.35 kU(A)/L (mean, 0.34 kU(A)/L; range, 0.34-2.3 kU(A)/L) in 10 of 15 children with outgrown WA. Conversely, in 12 of 14 children with persistent WA, the sIgE titers to ω-5 gliadin were still elevated (mean, 5.89 kU(A)/L; range, 0.34-16.3 kU(A)/L). CONCLUSIONS: sIgE to ω-5 gliadin can be used as an accurate alternative to potentially dangerous wheat food challenges in monitoring WA.

[Relationship between compliance with inhaled corticosteroids and changes in the fraction of exhaled nitric oxide during summer camp for asthmatic children].

BACKGROUND: Recently, the fraction of exhaled nitric oxide (FENO), which can be measured easily and noninvasively even in children, has attracted attention as a method of evaluating airway inflammation. The aim of this study was to investigate the relationship between compliance with inhaled corticosteroids (ICS) before a summer camp for asthmatic children and the changes in the FENO during camp. METHODS: Fifty asthmatic children (26 boys and 24 girls) aged 6-12 years old were recruited from the Fukuoka National Hospital Summer Camp between 2008 and 2010. We measured their FENO on the first and last day of camp. The children were taught appropriate inhalation methods by pediatric pulmonologists and nurses and performed ICS under their supervision every day during the camp. Before the camp, we asked the participants to complete a questionnaire regarding the use of ICS. The participants were classified into four groups according to their adherence to this therapy. The changes in FENO were then examined and compared among the groups. RESULTS: The FENO measured on the last day of camp was significantly lower than that measured on the first day of camp among children who tended to forget to perform ICS. However, no significant difference in the FENO measurements were observed during the camp, when the children were performing ICS every day. CONCLUSION: The FENO decreased significantly after only four days of camp in the poor compliance group. Therefore, teaching children the appropriate method for inhaling ICS is important, especially for children who tend to forget to perform ICS.

[Case of food protein-induced enterocolitis syndrome caused by short-neck clam ingestion].

A 6-year-old boy was referred for evaluation because he had several vomiting episodes, from the age of 2 years, following short-neck clam ingestion. He tested negative for short-neck clam-specific IgE just before visiting our hospital, and he was not allergic to other foods or shellfish. The patient had low levels of short-neck clam-specific IgE (1.04 UA/ml), and the skin prick test was positive for short-neck clam (4 mm). The lymphocyte stimulation test was positive (5305 counts per min (cpm), stimulation index (SI) =1211%) and the patch test was positive for short-neck clam ingestion. An oral challenge test with boiled short-neck clam induced abdominal pain and vomiting 2 h after ingestion, and the patient presented with increased peripheral leukocytes after 6 h. He was therefore diagnosed with food protein-induced enterocolitis syndrome (FPIES) due to short-neck clam ingestion. To our knowledge, this is the first case report of FPIES induced by the intake of shellfish.

Influence of maternal bifidobacteria on the establishment of bifidobacteria colonizing the gut in infants.

The aim of this study was to examine the influence of maternal intestinal and vaginal bifidobacteria on the establishment of bifidobacteria colonizing the gut in infants. Fecal samples from 110 healthy pregnant mothers within 1 mo before delivery and their babies at 1 mo of age and 100 vaginal swabs from the mother within 7 d before delivery were collected at a maternity hospital in Fukuoka city, Japan. The fecal and vaginal samples were assayed by PCR to detect Bifidobacterium species and by real-time PCR assays to estimate the bifidobacterial number. The detection of Bifidobacterium breve in the mothers' feces was significantly associated with increases in both the bifidobacterial counts and number of Bifidobacterium species in the babies' feces. In addition, a cesarean section was significantly associated with both a decrease in the counts and diversity of bifidobacteria in the babies' feces. The number of Bifidobacterium species detected in the vaginal swabs of mothers were not associated with either the bifidobacterial counts or the diversity of bifidobacteria in the babies' feces. The most important determinants of intestinal bifidobacteria in infants were the colonization of B. breve in the mothers' gut and vaginal delivery.

[Efficacy and safety of budesonide inhalation suspension nebulization by mesh nebulizer in Japanese infants and young children with bronchial asthma in 12-week, randomised, open study].

OBJECTIVE: This study evaluated the efficacy and safety of Budesonide Inhalation Suspension (BIS) nebulazation by mesh nebulizer in children ages 6 months to 4 years with moderate to severe persistent asthma. METHOD: This 12-week, randomized, open study involved 30 asthmatic children. They were randomized 3 different nebulizer groups, Pari TurboBoy +LC Plus nebulizer, Pari eMotion and Omron MicroAir NE-22U. BIS administered 0.25 mg once daily (qd). Efficacy was assessed by daily card. Safety was assessed by adverse event, plasma cortisol and growth. RESULT: Baseline concentrations of plasma cortisol were significantly high in the group of Omron MicroAir NE-22U compared to other group. Plasma cortisol were decreased significantly at 4 weeks in Omron MicroAir NE-22U compared with baseline, but those in no subjects decreased under normal range. Asthma symptoms were improved significantly from baseline to 12-week. CONCLUSION: This study demonstrate that usage of mesh nebulizer in BIS 0.25 mg qd is effective and safe in young asthmatic children.

Guidelines for diagnosis and management of pediatric food allergy in Japan.

In Japan, the prevalence of food allergy has been increasing and a variety of problems have emerged regarding what should be considered a food allergy. A treatment regimen consists of avoiding the offending food (elimination diet therapy) and receiving nourishment from alternative foods (substitutional diet therapy). There is a growing concern that confusion has resulted from the lack of a consensus on the procedures for diagnosing and treating food allergies. The Food Allergy Committee of the Japanese Society of Pediatric Allergy and Clinical Immunology established the "Guidelines for Diagnosis and Management of Pediatric Food Allergy." Definition, classification, pathophysiology, clinical disorders and management of food allergy are discussed and determined.

[Characteristics of shrimp allergy from childhood to adulthood in Japan].

OBJECTIVE: We examined profiles and clinical symptoms of shrimp allergy patients and investigated the correlation of shrimp-specific IgE to crustaceans-specific IgE, mollusks-specific IgE and shellfish-specific IgE. In addition, symptoms when eating crustaceans other than shrimp, mollusks and shellfish were examined, because they shared tropomyosin as a major allergen. METHODS: We examined 99 definitive shrimp allergy cases with questionnaire. RESULTS: Their onset started during either childhood or young adulthood. Symptoms appeared within an hour after ingestion of shrimp in 87.9% cases. The most common symptoms were skin symptoms, followed by oral allergic syndrome (OAS) like symptoms, respiratory symptoms. Anaphylaxis were observed in 61 cases including 2 anaphylactic shock cases. Among 99 shrimp allergy cases, 44 cases (64.7%) showed positive reaction to crabs out of 68 cases experiencing crab ingestion. Only 11 cases (17.5%) reacted against squid out of 63 cases with the experience in squid ingestion. Crab-specific IgE (C.I. 0.954, p < 0.001) and squid-specific IgE (C.I. 0.582, p > 0.001) were strongly correlated with shrimp-specific IgE. CONCLUSION: We conclude that a lot of cases with shrimp allergy react to crabs clinically, and which seem to be different from the reaction against mollusk and shellfish intake in spite of sharing tropomyosin as a major allergen among them.

Hypoallergenic and T cell reactive analogue peptides of bovine serum albumin, the major beef allergen.

We recently identified IgE-binding epitopes of bovine serum albumin (BSA), the major beef allergen, and found that the major epitope structure contains an EXXV motif. Here we report hypoallergenic analogue peptides of BSA that preserve T cell reactivity to retain the capacity to induce immunotolerance. Substitution of the glutamic acid in the EXXV sequence to aspartic acid leads to a remarkable reduction of IgE-binding ability and induces potent T cell proliferation. Moreover, in response to the substitutions, the production of INF-gamma is markedly increased compared with that elicited by the native peptides. Therefore, these analogue peptides represent potential candidates for specific immunotherapy.

High levels of urinary pentosidine, an advanced glycation end product, in children with acute exacerbation of atopic dermatitis: relationship with oxidative stress.

Pentosidine is an advanced glycation end product formed by sequential glycation and oxidation. The formation of pentosidine is increased in diseases associated with oxidative stress, such as inflammatory conditions. The aim of the present study was to determine the urinary concentration of pentosidine in atopic dermatitis (AD) and its relationship to the inflammatory status of AD. Urine samples of 32 children with AD and 30 age-matched healthy control subjects were assayed for pentosidine, pyrraline (another advanced glycation end product formed by nonoxidative glycation), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) (an established marker of oxidative stress). Of these 3 markers, urinary concentrations of pentosidine were significantly higher in patients with acute exacerbation of AD than in healthy controls and patients with stable AD. Urinary concentrations of 8-OHdG were significantly higher in AD patients with and without acute exacerbation than in healthy controls. Urinary pentosidine levels correlated significantly with those of 8-OHdG when all data of healthy controls and AD patients were plotted. In patients with acute exacerbation of AD, both urinary pentosidine and 8-OHdG significantly decreased after 7 to 9 days of treatment. Our findings in patients with acute exacerbation of AD suggest that pentosidine levels are partly determined by the prevailing oxidative stress in these patients.

Cytokine imbalance in hyper-IgE syndrome: reduced expression of transforming growth factor beta and interferon gamma genes in circulating activated T cells.

Hyper-IgE syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent infections and marked immunoglobulin (Ig)E elevation. To assess the proper T-cell defects of HIES, the cytokine profile of naturally activated T cells was compared between HIES, atopic dermatitis and chronic granulomatous disease (CGD). Intracellular flow cytometric analysis after in vitro stimulation showed no difference in the proportion of interferon (IFN)gamma- or interleukin 4 (IL-4)-producing T cells among these diseases. Quantitative polymerase chain reaction (PCR) for the cytokine genes was performed using circulating highly fractionated HLA-DR+ and HLA-DR- T cells. The IFNgamma/IL-4 or IFNgamma/IL-10 ratios were lower in HLA-DR+ T cells of HIES than in CGD (P = 0.0106, 0.0445), but did not differ between HIES and atopy. The transforming growth factor-beta (TGFbeta)/IL-4 ratio in HLA-DR+ T cells of HIES was lower than that of atopy (0.0106) or CGD (0.0062). The TGFbeta/IL-4 ratio in HLA-DR- T cells of HIES was also lower than that of atopy (0.0285). Stepwise logistic regression analysis identified TGFbeta/IL-4 ratios in HLA-DR+ (0.0001) or HLA-DR- (0.0086) T cells as the most powerful parameters to distinguish HIES from atopy and/or CGD. Serum IgE levels negatively correlated with IFNgamma/IL-4 (0.0108), IFNgamma/IL-10 (0.0254), or TGFbeta/IL-4 (0.0163) ratios in HLA-DR+, but not HLA-DR-, T cells. These results suggested that the in vivo activated T cells of HIES did not sufficiently express the IFNgamma and TGFbeta genes, which could affect IL-4-dependent IgE production. The reduced TGFbeta expression may involve the indigenous T-cell defects of HIES.