Rumiko Shibata

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 kUA/l in WA patients and <0.35 kUA/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.

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

Summary. 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)γ‐ 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 IFNγ/IL‐4 or IFNγ/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‐β (TGFβ)/IL‐4 ratio in HLA‐DR+ T cells of HIES was lower than that of atopy (0·0106) or CGD (0·0062). The TGFβ/IL‐4 ratio in HLA‐DR– T cells of HIES was also lower than that of atopy (0·0285). Stepwise logistic regression analysis identified TGFβ/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 IFNγ/IL‐4 (0·0108), IFNγ/IL‐10 (0·0254), or TGFβ/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 IFNγ and TGFβ genes, which could affect IL‐4‐dependent IgE production. The reduced TGFβ expression may involve the indigenous T‐cell defects of HIES.

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 physicians 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.

Distinct gene expression patterns of peripheral blood cells in hyper–IgE syndrome

Hyper‐immunoglobulin E (IgE) syndrome (HIES) is one of the primary immunodeficiency syndromes. Although the cytokine dysregulation is suggested to play a role in its pathophysiology, the causative gene has not yet been identified. To investigate the pathophysiology and candidate genes involved in this disease, we performed microarray analysis of unstimulated peripheral CD4+ T cells and CD14+ cells, as well as peripheral blood mononuclear cells (PBMNC) stimulated with Staphylococcus aureus isolated from HIES patients and healthy controls. By microarray analysis, 38 genes showed over 2‐fold differences between the HIES patients and healthy controls in purified CD14+ cells, although only small differences in the gene expression profiles were observed between the two groups in purified CD4+ T cells. RGC32 expression levels showed the greatest difference between the two groups, and were significantly  elevated  in  HIES  compared  with  those  in  severe  atopic  dermatitis or healthy controls using real‐time PCR. A significantly larger number of lysosome‐related genes were up‐regulated, and significantly larger number of genes related to cell growth and maintenance were down‐regulated in HIES. After the stimulation of PBMNC with Staphylococcus aureus, 51 genes showed over 3‐fold differences between HIES patients and healthy controls. A significantly large number of immunoglobulin‐related genes were up‐regulated in HIES. The distinct patterns of gene expression profiles and RGC32 expression levels will be useful for understanding the pathophysiology and for diagnosis of HIES, respectively.

Selective IgA Deficiency: Analysis of Ig Production in Vitro

The cellular basis of the pathogenesis of selective IgA deficiency (SIgAD) was investigated by examining surface immunoglobulin (SmIg) andin vitro pokeweed mitogen (PWM)-stimulated immunoglobulin (Ig) synthesis and by assaying in combination the counterpart lymphocytes from individuals with SIgAD and healthy donors. Peripheral blood lymphocytes (PBL) from 14 individuals with SIgAD synthesized normal amounts of IgG and IgM but did not synthesize normal amounts of IgA. Functional defects of lymphocytes for IgA synthesis were classified into four types: (i) B-lymphocyte dysfunction, (ii) increased function of suppressor T lymphocytes (Ts), (iii) decreased function of helper T lymphocytes (Th), and (iv) B-lymphocyte dysfunction and increased Ts function. The cells bearing SmIgG, SmIgM, and SmIgD were demonstrated at normal percentage ratios in all cases by immunofluorescent staining. The cells bearing SmIgA were at normal percentage ratios in the cases of T-lymphocyte dysfunction, while in the cases of B-lymphocyte defect SmIgA-bearing cells were reduced.

Trivalent cold recombinant influenza live vaccine in institutionalized children with bronchial asthma and patients with psychomotor retardation.

Twenty asthematic children and 48 patients with severe psychomotor retardation were inoculated intranasally with trivalent cold-adapted recombinant (CR) influenza vaccine containing CR-125 (H1N1), CR-159 (H3N2) and CRB-117 (B). The vaccinees were mostly seropositive. Severe adverse reactions or asthmatic attacks were not observed, but 7 (15%) of 48 vaccinees with severe psychomotor retardation developed mild to moderate fever. Significant antibody responses in hemagglutination-inhibition tests were demonstrated in 33 (49%) vaccinees to CR-125, 20 (29%) to CR-159 and 8 (12%) to CRB-117. Two nosocomial outbreaks of influenza were observed in the subsequent winter. During an outbreak with H3N2 in one ward of severe psychomotor retardation patients. 2 (11%) of 18 vaccinees became infected compared with 10 (48%) of 21 placebo controls in the same ward (P < 0.05). In the other outbreak, with influenza B virus, 2 (14%) of 14 vaccinees and 13 (52%) of 25 controls in the ward for asthmatic children were infected (P < 0.05). The results indicate that trivalent CR vaccine is safe and effective against nosocomial outbreaks of influenza.

Immunization of institutionalized asthmatic children and patients with psychomotor retardation using live attenuated cold-adapted reassortment influenza A H1N1, H3N2 and B vaccines

Live attenuated cold-adapted reassortant (CR) influenza virus vaccines were evaluated in institutionalized asthmatic children and severe psychomotor-retarded (SPR) patients. Almost all the vaccinees were seropositive to the vaccine strains before immunization. Trivalent CR vaccine (containing A H1N1 (CR-125), A H3N2 (CR-149) and B (CRB-117)), bivalent CR vaccine (CR-125 and CR-149) and monovalent CRB-117 were inoculated to 19 asthmatic children and 36 and 16 SPR patients, respectively. Overall 49, 22, and 11% of vaccinees were infected by A H1N1, A H3N2 or B vaccine viruses, respectively, as indicated by significant haemagglutination-inhibition (HI) antibody titre rises 4 weeks after inoculation. No severe adverse reactions associated with CR vaccination were observed in the handicapped patients. A nosocomial outbreak of influenza A H1N1 occurred in the ward with asthmatic children, but none of the 19 CR-trivalent vaccinees became infected. However, five of 20 non-vaccinees in the same ward, and ten of 30 vaccinees in another ward that received inactivated split vaccine became infected. The CR vaccines demonstrated significant protective effects against natural exposure to the A H1N1 virus, and were well tolerated and safe when given to patients with bronchial asthma and severe psychomotor retardation.

Pharyngoconjunctival fever caused by adenovirus type 11.

Among a group of hospitalized children in Fukuoka, southern Japan, an epidemic of pharyngoconjunctival fever-like disease caused by adenovirus type 11 was observed in the autumn of 1988. Of the 47 children studied 38 were seronegative in neutralizing antibody for adenovirus type 11 before the epidemic, and sero-conversion occurred in 16 (42%) including 5 subclinical cases. Of the 11 symptomatic patients the incidences of conjunctivitis, pharyngitis and fever were 91, 64 and 46%, respectively. Four patients (36%) had all three symptoms. Fifteen patients (94%) were boys. The sex predominance and high incidence of conjunctivitis suggested that infection may have been transmitted in the large bathroom where boys took baths together.

A Sensitive Solid Phase Radioimmunoassay for Secretory IgA

A sensitive solid phase radioimmunoassay method was established for the specific quantitative determination of secretory IgA (sIgA) by taking advantage of the dual antigenicities of sIgA, one specific for α‐chain and the other for secretory component (SC). The sIgA and IgA in the sample were first bound by anti‐IgA antibodies coated on the polystyrene tube, then the amount of bound sIgA was quantified by the use of 125I‐labeled anti‐SC antibodies. This method is quite sensitive and allows us to distinguish sIgA from IgA and free SC which usually coexist in exocrine secretions. Linear relationship was observed between the bound radioactivity of radioiodinated anti‐SC and the amount of sIgA in the range of 5 to 60 ng of sIgA.

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.