[Show abstract][Hide abstract] ABSTRACT: We occasionally see egg-allergic children who develop contact urticaria to hen's egg despite the absence of the overt symptoms on ingestion. The mechanisms remain to be elucidated.
Twenty-one subjects with positive reactions to 20-min patch tests for egg-white antigens were divided into subgroups with positive (n = 10) and negative (n = 11) results to oral challenge tests by the same antigens. We measured IgE antibody for egg white and its components, and IgE-binding activities to digestive enzyme-treated ovomucoid by RAST inhibition.
There were no significant differences in IgE antibody titers to egg white (positive vs negative: 30.3% vs 15.3%, P=0.130), ovomucoid (21.5% vs 10.2%, P= 0.078), ovotransferrin (9.9% vs 3.7%, P = 0.105), and lysozyme (3.4% vs 2.9%, P=0.944), except ovalbumin (16.8% vs 5.6%, P=0.024), between the positive and negative subjects in the provocation tests. In contrast, the concentration (1.93 microg/ml) of pepsin-treated ovomucoid needed for 50% RAST inhibition in the challenge-positive subjects was significantly (P=0.0003) lower than that (114.9 microg/ml) of negative subjects. Similar but less significant differences were obtained when ovomucoid fragments treated with chymotrypsin (0.91 microg/ml vs 6.86 microg/ml, P=0.014) and trypsin (0.75 microg/ml vs 4.67 microg/ml, P= 0.041) were used as inhibitors.
We suggest that IgE antibodies from subjects showing contact urticaria despite the absence of reactions to the ingestion of egg white recognize the epitope(s) unstable to digestive enzymes.
[Show abstract][Hide abstract] ABSTRACT: We report on a 9-year-old boy with the hyper-IgM syndrome who presented with rapid impairment of consciousness. The brain CT scan showed multiple round lucencies, and the brain histology revealed necrotizing toxoplasmic encephalitis. This patient, whose CD40/CD40 ligand system was impaired, indicates the importance of this system for defence against toxoplasmic infection. CONCLUSION: Although disseminated toxoplasmosis is a rare complication of the hyper-IgM syndrome, it must be included in the differential diagnosis of infections.
European Journal of Pediatrics 10/1998; 157(9):735-7. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: One hundred and ninety one subjects showing histories of immediate hypersensitive response to egg white ingestion and/or positive IgE antibody titers specific for egg white were enrolled in double-blind placebo-controlled oral challenge with freeze and dried, heated or heated and ovomucoid-depleted egg white antigens. Seventy seven were male and 114 female, and their ages ranged from 11 month to 10 years 5 month; 118 of them had atopic dermatitis, seven had asthma and 33 had both atopic dermatitis and bronchial asthma and 33 had urticaria. One hundred four children developed 147 positive symptoms including 131 immediate reactions and 16 non-immediate reactions by oral challenge tests. Respiratory symptoms were observed in 25 cases (17%) including cough alone in 12 cases (8.2%), and both wheezing and cough in 13 cases (8.8%). These were all observed as immediate reactions and accompanied with dermal symptoms. Frequency of respiratory symptoms correlated with specific IgE antibody titers for egg white. Heated and ovomucoid-depleted egg white was more hypoallergenic that heated or freeze and dried egg white with respect to respiratory symptoms as well as other symptoms. We concluded that respiratory symptoms were provoked through oral challenges with egg white in a part of egg-allergic children.
[Show abstract][Hide abstract] ABSTRACT: No egg white products have been clearly proven to be hypoallergenic. The role of egg white proteins in allergic reactions to eggs is still debatable.
This study was designed to determine the importance of ovomucoid, an egg white protein, in the development of allergies to egg white.
We performed a double-blind, placebo-controlled food challenge in subjects with high levels of IgE antibodies for egg white to compare the allergenicities of heated and ovomucoid-depleted egg white, freeze-dried egg white, and heated egg white. Levels of IgE antibodies for egg white, ovomucoid, ovalbumin, ovotransferrin, and lysozyme were measured in serum by RAST.
Twenty-one of 38 subjects with positive challenge responses to freeze-dried egg white had negative challenge responses to heated egg white, whereas 16 of 17 subjects (94.1%) with positive responses to heated egg white did not respond to the heated and ovomucoid-depleted egg white challenge. The subjects with positive challenge responses to freeze-dried egg white tended to have higher IgE antibody values to ovomucoid than those with negative responses. IgE antibody levels to ovomucoid were significantly higher in subjects with positive responses to a challenge with heated egg white than in those with no response. There were no significant differences in the levels of IgE antibodies to the other proteins, except ovomucoid, in the negative-response and positive-response groups in challenge tests with freeze-dried and heated egg white.
The heated and ovomucoid-depleted egg white preparation was less allergenic than heated or freeze-dried preparations. Ovomucoid has a more important role in the pathogenesis of allergic reactions to egg white than other proteins in egg white.
Journal of Allergy and Clinical Immunology 09/1997; 100(2):171-6. · 12.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A girl, 5.7 years old, gained tolerance to egg white ingestion in spite of high immunoglobulin E (IgE) antibody titers to egg white but retained contact urticaria against egg white. She developed atopic dermatitis on her face at 2 months of age and showed high IgE antibody titers to egg white and cow's milk. Accidental ingestion of egg products initiated immediate symptoms such as wheezing, urticaria, erythema and edema of the eyelids and conjunctiva three times. These symptoms were confirmed by challenge tests using boiled egg white at 3.9 years of age. She also reacted positively to a 20 min patch test on her volar arm with raw egg white. However, there were no reactions to the oral challenge test by boiled egg and freeze-dried egg white at 5.1 and 5.7 years of age, respectively. This non-responsiveness was confirmed by a double-blind, placebo-controlled food challenge using freeze-dried egg white. Nevertheless, she showed positive reactions to a 20 min patch test with freeze-dried egg white. Her IgE antibody titers to the egg white components including ovomucoid, ovalbumin, ovotransferrin and lysozyme as well as egg white were high from 2.9 to 5.7 years old. Her IgE antibody titers for the ovomucoid fragments digested by pepsin, chymotrypsin and trypsin were not lower than those of positive control subjects. The binding activity of IgE antibody to ovomucoid, however, decreased from 2.9 to 5.6 years as shown by radioallergosorbent test (RAST) inhibition assays. The IgE antibody showed weaker binding activity to pepsin- and chymotrypsin-digested ovomucoid that were filtered through cut-off 10,000 filter at the age of 2.1 and 5.7 years. We speculated that the maturation of secretion of digestive enzymes was involved in the mechanisms of the acquisition of tolerance to egg white ingestion in spite of the persistence of contact urticaria.
[Show abstract][Hide abstract] ABSTRACT: Severe combined immunodeficiency (SCID) with a normal number of B-lymphocytes usually demonstrates an X-linked inheritance and now is regarded as an interleukin-2-receptor (IL-2R) gamma-chain gene defect. Here, we report the characterization of mutations in the IL-2R gamma-chain gene of six unrelated SCID patients. One large deletion, one short deletion, one nonsense mutation and three single missense mutations were identified. The missense mutations were located near the motifs common to members of the class I cytokine receptor family. Two of the missense mutations were the same as previously reported in spite of the difference of ethnic backgrounds. The remaining four patients had newly identified mutations. CONCLUSION: Our results emphasize the broad molecular heterogeneity of X-linked SCID and suggest the presence of mutational "hot spots" within the IL-2R gamma-chain gene.
European Journal of Pediatrics 01/1997; 155(12):1018-24. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immediate hypersensitive reactions induced by buckwheat ingestion are considered to be IgE-mediated. Some subjects, however, develop no immediate adverse reactions after buckwheat ingestion despite high levels of buckwheat-specific antigens IgE. The mechanism is unknown.
To investigate the mechanisms.
RAST for buckwheat and rice and RAST inhibition between these antigens were performed using sera from 23 buckwheat-sensitive subjects and 30 buckwheat-tolerant subjects who had IgE antibodies for both buckwheat and rice.
RAST values for buckwheat and rice were significantly correlated with each other (P < .01) in the buckwheat-tolerant group, but not in the buckwheat-sensitive group. This suggests the IgE antibodies from the subjects without any overt symptoms after buckwheat ingestion recognize the cross-reactive epitope between buckwheat and rice, whereas the IgE antibodies from those with immediate reactions to buckwheat ingestion do not. RAST inhibition assays were performed to evaluate this. RAST inhibition of heterogeneous combination of inhibitor and disc antigen such as rice and buckwheat was significantly smaller than that of homologous combination of rice and rice or buckwheat and buckwheat in the group with immediate symptoms after buckwheat ingestion. There was no significant difference in RAST inhibition between homologous and heterogeneous combinations in the group without the symptoms.
There was cross-reactivity with IgE antibodies between buckwheat and rice and IgE antibodies from the buckwheat-tolerant subjects with high levels of IgE antibodies from the buckwheat might recognize the epitopes on buckwheat antigens which cross-react with rice antigens, whereas IgE antibodies from the buckwheat-sensitive subjects might bind to buckwheat-specific epitopes.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/1995; 75(1):56-61. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IgE is considered to be involved in immediate hypersensitive reactions (IHR) following egg ingestion. IgE antibody levels to egg-white (EW) antigens in the IHR-positive group (n = 19, mean age +/- SD = 5.2 +/- 4.5 yr) were higher than those in the IHR-negative group (n = 13, mean of age +/- SD = 3.6 +/- 2.2 yr). However, even in the IHR-negative group, some patients showed high IgE to EW. RAST inhibition tests with heat-treated (100 degrees C, 5, 10, and 30 min) egg-white antigens were performed on 13 serum samples from subjects with IHR and 9 serum samples from subjects without IHR. Heat treatment decreased the IgE-binding activity of egg white and it was speculated that IgE from IHR-negative subjects bound to relatively heat-unstable sites of egg-white antigens. Furthermore, we selected IHR-negative subjects (n = 8, mean of age +/- SD = 3.0 +/- 1.7 yr) with higher IgE antibody levels than the lowest limit of IgE to EW of the IHR-positive group and compared IgE to ovomucoid (OM), ovalbumin (OA), conalbumin (CA), and lysozyme (Ly) between these IHR-negative and positive groups. IgE-binding activities to egg-white components, including OA, CA, and Ly but not OM, were significantly decreased with heat treatment. The IHR-negative group showed significantly lower IgE to OM (untreated, 5, 10, 30 min treatment) and 5 min treated OA alone than the IHR-positive group, while no difference was found in IgE to other components between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
[Show abstract][Hide abstract] ABSTRACT: We investigated the patterns of DNA rearrangements at loci for Ig JH genes in patients with severe combined immunodeficiency (SCID). Four SCID patients without B cells (B- SCID) and four SCID patients with B cells (B+ SCID) were examined. Bone marrow cells of these patients were transformed with EBV. The majority of the transformed cells from three B- SCID patients had the germline configuration at their JH gene loci. The rearranged fragments from one patient were analyzed extensively. The rearranged regions in all of the fragments had a common structure wherein two fragments derived from the JH-S mu region were connected inversely. The possible presence of rearranged forms of VHDJH and DHQ52JH sequences in bone marrow cells of two B- SCID patients were examined directly by the polymerase chain reaction (PCR) method. In one patient, we found neither a VHDJH sequence nor a DHQ52JH sequence within the range of sensitivity of the PCR method. In another patient, we found a VHDJH sequence at an extremely low level and DHQ52JH sequences at a relatively low level. Either RAG-1 or RAG-2 gene was not expressed in the B- SCID-derived cell lines. B+ SCID patients did not show any abnormalities in terms of VHDJH rearrangements. These results indicate that B- SCID may be caused by defects in factors involved in V(D)J rearrangements.
The Journal of Immunology 07/1994; 152(11):5504-13. · 5.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The X chromosome inactivation analysis of eight female relatives was performed to elucidate the X chromosome gene defect of six male hypogammaglobulinaemic individuals. The patients had diminished numbers of circulating B-cells and no relevant family history. The methylation status of three X-linked genes, phosphoglycerate kinase, hypoxanthine phosphoribosyl transferase and DXS255, was determined on DNA from Epstein-Barr virus-transformed B-cell lines established from the female relatives. The methylation pattern of at least one gene was informative in all eight females examined. While both alleles were equally methylated in four of eight females, the remaining four female relatives of three hypogammaglobulinaemia patients exhibited a non-random methylation pattern in their B-cells, suggesting that these three patients represented sporadic cases of X-linked agammaglobulinaemia (XLA). The clinical or immunological status of these three patients did not differ from the remaining two who had early onset hypogammaglobulinaemia and who were tentatively diagnosed as having common variable immunodeficiency. The sixth patient had recurrent infections after undergoing surgical removal of a brain tumour at 22 years of age, although his immunological features did not distinguish him from the other patients. X chromosome inactivation analysis can be useful in differentiating XLA from hypogammaglobulinaemia in male patients.
European Journal of Pediatrics 12/1993; 152(11):900-4. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immediate hypersensitive reactions (IHR) induced by buckwheat ingestion are considered to be IgE-mediated. However we found 28 subjects without IHR to buckwheat ingestion out of 46 subjects who had positive RAST values for both buckwheat and rice antigens. The IHR-positive group showed significantly higher RAST values for buckwheat antigens (p < 0.01) but lower RAST values for rice antigens (p < 0.01) than did the IHR-negative group. RAST values for buckwheat and rice were significantly correlated with each other (p < 0.01) in the IHR-negative group, but not in the IHR-positive group. An effective dose-dependent inhibition was obtained in a RAST inhibition assay between homologous combinations of inhibitor and disc antigens such as rice and rice or buckwheat and buckwheat. The IHR-positive group showed no significant RAST inhibition between heterogeneous combinations of rice and buckwheat antigens. In contrast, the IHR-negative group showed a significant decrease in IgE binding even in the RAST inhibition assay between heterogenous combinations. These results led to the conclusion that there is cross-reactivity with IgE antibodies between buckwheat and rice and that IgE antibodies from IHR-negative subjects might recognize the epitopes on buckwheat antigens which cross react with rice antigens, whereas IgE antibodies from IHR-positive subjects might bind to buckwheat-specific epitopes.
[Show abstract][Hide abstract] ABSTRACT: In a previous study (Immunogenetics 1988. 27:330) with Epstein-Barr virus, we established lines of precursor B cells from bone marrow cells of a patient with severe combined immunodeficiency in whom the numbers of B cells and T cells were markedly reduced. Although based on their surface markers these cell lines appeared to be at an early stage of B cell differentiation, the gene loci for immunoglobulin heavy chains (IgH) retained the germ-line configuration on both chromosomes in almost all the transformants. In this study, we found that the enhancer sequence, located between the JH and mu genes, was hypomethylated and an abundance of the germ-line Cmu transcript was detected in these cell lines by Northern hybridization. These results suggest that the chromatin structure of the IgH gene locus in these cell lines is accessible to VDJ recombinase and is able to participate fully in DNA rearrangement. By contrast, we did not detect transcripts of the RAG-1 and RAG-2 genes, which are required for V(D)J recombination at gene loci for immunoglobulin and T cell receptors. Thus, it seems likely that these cell lines fail to initiate the V(D)J recombination process because of some deficiency in the formation of VDJ recombinase, which includes the inability to express RAG genes.
European Journal of Immunology 07/1993; 23(6):1401-4. · 4.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The methylation pattern of three X-linked genes, phosphoglycerate kinase (PGK), hypoxanthine phosphoribosyl transferase (HPRT) and DXS255 detected by hypervariable M27 beta probe, was analysed to determine the proportion of aplastic anaemia (AA) with clonal haematopoiesis in Japanese children. Methylation analysis was performed on DNA from separated granulocytes and compared to that of bone marrow derived fibroblasts to exclude selective lyonization in all somatic cells. Of 20 female patients examined, the methylation pattern of at least one gene was informative in granulocyte DNA from 18 patients (90%). Of these, 8/20 patients (40%) were heterozygous for PGK, 8/18 (44%) were heterozygous for HPRT and 17/18 (94%) were heterozygous for DXS255. In 14/18 patients both alleles were equally methylated. Four patients exhibited a unilateral methylation pattern in their granulocytes. The same unilateral pattern was again demonstrated in fibroblasts from two of the four patients suggesting that in the latter one X chromosome was selectively inactivated in all of the somatic cells. The remaining two patients showed a unilateral methylation pattern that was restricted to their granulocytes, suggesting the existence of true clonal haematopoiesis. They responded well to antilymphocyte globulin (ALG) and presently have no evidence of a clonal disorder such as myelodysplastic syndrome (MDS) or paroxysmal nocturnal haemoglobinuria (PNH). Although these results indicate that some children with AA exhibit clonal haematopoiesis, analysis of a greater number of subjects will be required to establish the clinical value of clonal haematopoiesis in patients with AA.
British Journal of Haematology 06/1993; 84(1):137-43. · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cross-reactivity between rice, wheat, corn, Japanese millet and Italian millet in Poaceae family were studied by absorption test, radioallergosorbent test (RAST), and RAST inhibition assay. In absorption test using Phadebas RAST discs, more than 50% absorption of IgE antibodies was observed between rice, wheat and corn. There were significant correlations of RAST values for cereal grains including rice, wheat, corn, Japanese millet and Italian millet. RAST inhibition assay between every combinations of these cereals showed dose-dependent decrease in IgE-binding. These data indicated cross-reactivity with IgE antibodies between the five cereals in Poaceae family. RAST values for RP16KD significantly correlated with those for Italian millet as well as rice but not with those for corn and wheat. There was a trend of positive correlation between RAST values for RP16KD and Japanese millet. In RAST inhibition assay using sera with positive RAST for these five cereal grains and RP16KD, RP16KD inhibited IgE-binding to these all cereal discs in dose-dependent manner. Similarly, all of five cereal grain extracts showed an effective diminution in IgE-binding to RP16KD disc. These results indicated possible participation of IgE-binding structure on RP16KD in cross-reactivity between these cereal grains in Poaceae family.
[Show abstract][Hide abstract] ABSTRACT: Recently Aspergillus restrictus, a species of osmophilic fungi, has been found to be widely distributed in our inhabited environment. The authors reported previously that the prevalence of hypersensitivity to this fungal species determined by skin prick test and radioallergosorbent test (RAST) was comparable with that to Aspergillus fumigatus. In this study, the allergenic relationships between the two fungi were examined by RAST and RAST inhibition tests in which A. restrictus extracts prepared from mycelial mats of two different strains cultured in M40Y liquid medium and A. fumigatus, one made from a mycelial mat cultured in YNB liquid medium containing 3% sucrose, were used. In the RAST inhibition tests using a serum pool obtained from five patients with highly positive RAST to these species, the two extracts of A. restrictus inhibited RAST to A. fumigatus by over 80%, and A. fumigatus extract inhibited RAST to the two strains of A. restrictus by approximately 75%. In A. fumigatus RAST inhibition tests using individual sera with positive A. fumigatus RAST, a strong inhibition (greater than 60%) elicited by each extract of A. restrictus was observed in 5 of 8 sera tested. In RAST, nine of 11 serum samples with positive RAST to A. fumigatus showed positive RAST to both strains of A. restrictus. There was a significant correlation between the RAST values of the two fungal species. These results give evidence of the presence of shared allergenic components between the two fungi, and indicate that these components may contain part of major allergens of A. fumigatus.
[Show abstract][Hide abstract] ABSTRACT: Recently large amounts of Aspergillus restrictus, a species of osmophilic fungi, have been detected in house dust using culture media with low water activity. But little attention has been paid to this fungus as an allergen. In the present study, the authors examined the allergenic activity of A. restrictus by skin prick tests and radioallergosorbent tests (RAST) on 94 asthmatic patients (mean age 12.0, range 3-18). Aspergillus fumigatus, Alternaria alternata and house dust were used for comparison. In the skin prick tests, A. restrictus, A. fumigatus, A. alternata and house dust elicited positive reactions in 8 (8.5%), 8 (8.5%), 15 (16.0%) and 69 (73.4%) patients, respectively. RAST showed positive reactions in 27 (28.7%) subjects for A. restrictus, 22 (23.4%) for A. fumigatus, 35 (37.2%) for A. alternata, and 75 (79.8%) for house dust. These results indicated that some asthmatic individuals showed immediate-type hypersensitivity to A. restrictus, and the prevalence of hypersensitivity of A. restrictus determined by skin prick tests and RAST was comparable with that of A. fumigatus but lower than that of A. alternata or house dust. This indicates that this fungal species may be of importance as a causative agent in atopic diseases.
[Show abstract][Hide abstract] ABSTRACT: Recently, moulds are considered to be important allergens for bronchial asthma. To confirm this fact, 76 asthmatic patients (mean age 12.5, range 6-17 years) admitted to National Chubu Hospital were investigated for 16 different mould allergens by Pharmacia RAST RIA to measure specific-IgE for moulds. The results were as follows. 1) The frequency of positive RASTs (score greater than or equal to 2) varied from 4% to 21% depending on the allergen. Because 21 patients were RAST positive to one or more allergens, ultimately 26 patients (34%) appeared to be RAST positive to more than one of the 16 mould allergens. 2) According to the number of positive RASTs, the patients were divided into 3 groups, i.e. group 1 with more than five, group 2 with less than four and group 3 with zero. The ratio of patients with severe and moderate asthma to the total subjects was not significantly different between three groups before admission, but significantly high in group 1 and group 2 in order compared to groups 3 (chi 2(4)df = 18.81, p less than 0.005) one year after admission. This tendency was already apparent even one month after admission. 3) The frequency of positive RASTs for mould allergens was higher in patients with atopic dermatitis than in those without it. From these results, positive RAST for mould allergen seems to have considerable influence to intractable asthma and atopic dermatitis in young asthmatic patients.
[Show abstract][Hide abstract] ABSTRACT: Amlexanox, an anti-allergic drug, showed a concentration-dependent inhibition against hrIL-3-induced enhancement of in vitro histamine release from human leukocytes by anti-IgE. The significant inhibitory action of amlexanox was observed in one out of nine and six out of nine allergic subjects at concentrations of 10(-5) M and 10(-4) M, respectively. This means that the inhibitory effect of amlexanox varied from patient to patient. Post-treatment as well as simultaneous treatment with amlexanox produced an inhibitory action on the enhancing effect of hrIL-3, suggesting that hrIL-3-induced enhancement of releasability is a reversible reaction. AA-861, OKY-046, superoxide dismutase and prostaglandin E2 showed no effects on the hrIL-3-induced enhancement of histamine releasability. The inhibitory action of amlexamox to the hrIL-3-induced enhancement of histamine releasability may be a new anti-allergic mechanism, details of which remains unclear.
[Show abstract][Hide abstract] ABSTRACT: We established a transformed B cell line expressing both IgM and IgG on the cell surface from a patient with hyper IgM immunodeficiency using Epstein-Barr viruses. DNA and RNA of the cells were analyzed. DNA rearrangements of Ig JH gene loci were observed on both chromosomes. Cloning and DNA sequence analyses showed that one has a VHDHJH structure while the other has a DHJH structure. Southern hybridization with 5'-S mu and S gamma region-containing probes indicated germline configuration in the switch regions of mu and gamma genes on both chromosomes. To test expression of mu and gamma chains in the transformed cells at the mRNA-level, we used the polymerase chain reaction with three kinds of synthetic oligonucleotides as primers, one of which was part of the VH gene, while the other two were complementary to parts of C mu and C gamma genes. Sequence analysis of the amplified products showed that the same VHDHJH sequence is directly connected with either the C mu or the C gamma sequence in the mRNAs. This is direct evidence showing that in double isotype-bearing cells one VHDHJH exon in the transcript is alternatively spliced to C mu or C gamma without DNA rearrangement. The defect in this disease could be at the S-S recombination stage.
Journal of Clinical Investigation 07/1990; 85(6):1722-7. · 12.81 Impact Factor