Association of the MMP9 gene with childhood cedar pollen sensitization and pollinosis

Matrix metalloproteinase 9 (MMP9) gene has been shown to be involved in the pathogenesis of allergic rhinitis (AR) and asthma. Previous studies suggested that single-nucleotide polymorphisms (SNPs) of the MMP9 gene conferred a risk for childhood asthma. However, whether the SNPs confer a risk for AR has not been previously investigated. The objective of this study was to investigate whether SNPs of the MMP9 gene are associated with risk of seasonal AR (pollinosis), perennial AR and allergen sensitization. A total of 670 school children were recruited in Japan and genotyped for functional polymorphism in the promoter (-1590C/T: rs3918242) and three amino-acid substitutions (R297Q: rs17576; P574R: rs2250889; R668Q: rs17577). Serum levels of total and specific IgE were determined. Disease status and other clinical characteristics of the subjects were investigated using a questionnaire. Associations between the MMP9 SNPs and both AR and serum IgE levels were evaluated. -1590C/T showed significant association with cedar pollinosis (corrected P (Pcor)=0.039). R668Q was in strong linkage disequilibrium (LD) with -1590C/T and showed significant association with cedar pollinosis (Pcor=0.023) and serum cedar pollen-specific IgE level (Pcor=0.022). A haplotype associated with -1590T and 668Q showed a significant association with cedar pollinosis, orchard grass pollinosis and cedar pollen-specific IgE (Pcor=0.0012, Pcor=0.0059 and Pcor=0.0041, respectively). R297Q and P574R were in weak LD with the rest of the SNPs and did not show significant association with disease. Compared with wild-type MMP9 protein (279R-574P-668R), a variant enzyme (279R-574P-668Q) that showed association with pollinosis had lower activity. However, lower enzyme activity was not associated with disease risk because another variant (279Q-574R-668R) showed lower enzyme activity but was not associated with pollinosis. The -1590T allele and its corresponding haplotype was associated with higher promoter activity and with pollen-specific IgE levels and pollinosis, suggesting that -1590C/T may have more impact on sensitization and disease development than R668Q. Our results suggest that the MMP9 gene confers susceptibility to cedar pollinosis in Japanese children. The MMP9 gene may be associated with pollinosis through sensitization processes.     

Genotypes and haplotypes of CCR2 and CCR3 genes in Japanese cedar pollinosis

Whole genome scan analyses have revealed that the chromosomal region 3p21.3, which contains a gene cluster of the CC chemokine receptor, is possibly critical for the pathogenesis of allergic inflammation. Japanese cedar pollinosis is mediated by a type I allergy and induces seasonal rhinitis and conjunctivitis in humans as the most common form of hay fever in spring in Japan, although the candidate genes for cedar pollinosis remain to be elucidated. We sequenced CCR1, CCR2, CCR3, CCR5, and CCXCR1 using the PCR restriction fragment length polymorphism method in subjects with cedar pollinosis and controls. We found 8 polymorphisms of A111G, Arg127Cys and Arg252Gln in CCXCR1, T885C in CCR1, Val64Ile and T780C in CCR2, T51C in CCR3 and Arg223Gln in CCR5. The transmission disequilibrium test using 60 children with pollinosis and their parents and an association study using unrelated adult subjects (151 patients and 157 controls) showed a significant association of 64Ile in CCR2 and 51C in CCR3 with cedar pollinosis. The frequency of haplotype 64Ile/780C/51C in pollinosis was significantly higher than in controls. Our results suggest that CCR2 and CCR3 genes are candidate genes for Japanese cedar pollinosis.     

Probiotics in the treatment of Japanese cedar pollinosis: a double-blind placebo-controlled trial

BACKGROUND: Probiotic bacteria may be effective in the treatment of allergic inflammation and food allergy, but efficacy and underlying mechanisms remain unclear. OBJECTIVE: The present study investigated the effects of probiotic strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis (JCPsis). METHODS: In a randomized, double-blind, placebo-controlled trial, 44 JCPsis subjects received BB536 or placebo for 13 weeks during the pollen season. Subjective symptoms and self-care measures were recorded daily and blood samples were taken before and during intervention to measure blood levels of parameters related to JCPsis. RESULTS: BB536 intake was associated with a significant reduction in number of subjects prematurely terminated due to severe symptoms and pollinosis medication (P=0.0057 vs. placebo group). Comparison of subjective symptom scores indicated significant decreases in rhinorrhea, nasal blockage and composite scores in the BB536 group compared with the placebo group. Comparison of medical scores showed marked improvements in all symptoms on BB536 intake. A T-helper type 2 (Th2)-skewed immune response occurring along with pollen dispersion was observed. BB536 significantly suppressed increases in plasma thymus- and activation-regulated chemokine and tended to suppress elevations of Japanese cedar pollen (JCP)-specific IgE. CONCLUSION: These results suggest the efficacy of BB536 in relieving JCPsis symptoms, probably through the modulation of Th2-skewed immune response.     

ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics

BACKGROUND: A disintegrin and metalloprotease 33 (ADAM33) is expressed in the lung by fibroblasts and bronchial smooth muscle cells. Given its structure and cellular provenance, ADAM33 may be associated with airway remodelling and bronchial hyper-responsiveness. Single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 gene have previously been associated with asthma susceptibility in the Caucasian population. OBJECTIVE AND METHODS: To assess whether genetic variants of ADAM33 are related to asthma in a Korean population, we conducted an association study of the ADAM33 gene with asthma susceptibility, bronchial hyper-reactivity and serum IgE in Korean asthmatics (n=326) and normal controls (n=151). Five of the 14 polymorphisms originally reported to be associated with asthma development (S1 G>A, T1 T>C, V-1 C>A, V1 T>A, V4 C>G) were genotyped using single base extension and electrophoresis. Haplotypes and their frequencies were inferred using the algorithm implemented by the software Arlequin. Allele frequencies of each SNP and haplotypes were compared between the patients and the normal controls using logistic regression analysis. RESULTS: There was no significant difference in the distribution of SNPs and the six haplotypes between asthmatics and normal controls. All single SNPs and six haplotypes in ADAM33 were also analysed for the association with level of PC(20) using general linear models. The distribution of the T1 T>C SNP and one haplotype (ht4: GCGG) showed significant association with log-transformed PC(20) methacholine level in the asthma patients (P=0.03 and 0.0007, respectively, using a co-dominant model). CONCLUSION: Polymorphism of ADAM33 may contribute to development of BHR in asthma.     

Association of serum interleukin‐33 level and the interleukin‐33 genetic variant with Japanese cedar pollinosis

Background IL‐33, an IL‐1‐like cytokine, is a ligand for IL1RL1, which is an important effector molecule of type 2 T helper responses. Although IL‐33/IL1RL1 interaction has been suggested to be important in induction of allergic airway inflammation, serum levels of IL‐33 and the genetic influences of the polymorphisms of IL‐33 in human allergic diseases are unclear. Objective The aim of this study was to examine whether the serum IL‐33 level and polymorphisms in IL‐33 are associated with Japanese cedar (JC) pollinosis, the most common form of allergic rhinitis, and a major public health problem, in Japan. Methods We performed linkage disequilibrium (LD) mapping of the gene using the HapMap database, and two selected tag single nucleotide polymorphisms were genotyped. We conducted an association study of IL‐33 (JC pollinosis, n=170; normal controls, n=100) and measured the IL‐33 levels in sera of the 270 subjects by ELISA. Results Serum levels of IL‐33 were significantly higher in patients with JC pollinosis (P=0.0018) than in controls. In genetic association analysis, we found a positive association between the polymorphism and JC pollinosis (P=0.048). Conclusion Our results support a role for IL‐33 in the pathogenesis of JC pollinosis.     

Japanese cedar pollinosis is a risk factor for bronchial asthma in Japanese adult asthmatics]

It is well known that allergic rhinitis and asthma often coexist in the same patients. Here, we investigated the influence of Japanese cedar pollinosis on the exacerbation of asthma investigated by questionnaire, daily asthma diary, and peak expiratory flow (PEF) monitoring. Furthermore, airway responsiveness to histamine before pollen season was also investigated in some patients. 333 adult patients with asthma were enrolled into the study and 116 patients (34.8%) were suffering from Japanese cedar pollinosis diagnosed by the presence of nasal allergic symptoms during pollen season and high titer of Japanese cedar-specific IgE antibody. Exacerbation of asthma symptoms, including wheezing, dyspnea, cough, and sputum, was detected in 41 of 116 patients (35.3%) during pollen season. Decrease in morning PEF more than 10% compared with the baseline values before pollen season was observed in 13 of 41 patients (11.2% of total asthmatic patients who complicated with Japanese cedar pollinosis). No significant differences in airway responsiveness to histamine and the titer of Japanese cedar-specific IgE antibodies before pollen season were observed between the patients whose asthma exacerbated and the patients whose asthma was not exacerbated. These results suggest that Japanese cedar pollinosis is one of risk factors for asthma in Japanese adult patients with asthma.     

Association of single nucleotide polymorphisms in the eosinophil peroxidase gene with Japanese cedar pollinosis

BACKGROUND: Japanese cedar pollinosis is the most common form of hay fever in spring in Japan. We have previously demonstrated that single nucleotide polymorphism Pro358Leu of exon 7 in the eosinophil peroxidase (EPO) gene is associated with cedar pollinosis, although the association has not been confirmed by analysis of the whole gene in a different population. METHODS: We sequenced all exons of the EPO gene in 60 children with pollinosis and their parents using the PCR-restriction fragment length polymorphism method. RESULTS: We found 8 polymorphisms, Ile40Met, Gln122His, Arg202Arg (A660G), Asn303Asn (C909T), Arg326Pro, Arg326His, Pro358Leu, and Asn572Ty, in the EPO gene. As a result of the transmission disequilibrium test, we recognized significant transmissions of 202Arg (660G) in exon 6 in addition to 358Leu of exon 7 in the EPO gene of affected children. CONCLUSIONS: Our results might indicate that polymorphisms of the EPO gene are associated with Japanese cedar pollinosis.     

ADAM33 genetic polymorphisms, smoking, and rhinoconjunctivitis in Japanese women: the Kyushu Okinawa Maternal and Child Health Study

Two previous studies have demonstrated a significant relationship between ADAM33 single nucleotide polymorphisms (SNPs) and allergic rhinitis. Here, we investigated this issue in young adult Japanese women. The study included 393 women who met the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC) for rhinoconjunctivitis. Controls included 767 women without rhinoconjunctivitis according to the ISAAC criteria who had not been diagnosed with allergic rhinitis by a doctor. The GC genotype of rs2787094, the CT genotype of rs628977, and the haplotype containing the rs2787094 C allele, the rs628977 T allele, the rs2853209 T allele, and the rs612709 G allele were significantly inversely associated with rhinoconjunctivitis. The AA genotype of rs2853209, the GA genotype of rs612709, and the haplotype carrying the rs2787094 G allele, the rs628977 C allele, the rs2853209 A allele, and the rs612709 G allele were significantly positively associated with rhinoconjunctivitis. A significant inverse relationship between rs628977 and rhinoconjunctivitis was demonstrated only in women who had never smoked, indicating a significant interaction between rs628977 and smoking. Our results suggest that SNPs and haplotypes in the ADAM33 gene are associated with rhinoconjunctivitis. This study is the first to demonstrate an interaction between rs628977 and smoking that affects rhinoconjunctivitis.     

Update on epidemiology of pollinosis in Japan: changes over the last 10 years

A nationwide epidemiologic survey of atopic diseases including allergic pollinosis was conducted in 9656 Japanese otorhinolaryngologists and their family members during the Japanese cedar pollen dispersion season in 2008 using methods identical to a previous survey that was performed in 1998. The survey response rate was 37.7% (compared with 42.8% in 1998). The overall prevalence rate of Japanese cedar pollinosis was 26.5%, which is an increase of approximately 9% from that noted in 1998. Similar increases were observed in all age groups, and the prevalence rate was similar between male and female respondents. A unimodal distribution was observed in male and female subjects, with a peak in both men and women aged in their 40s. Nationwide, a consistent positive relation was observed between the prevalence of Japanese cedar pollinosis and the regional Japanese cedar pollen counts. The prevalence rate of pollinosis other than Japanese cedar pollinosis and of perennial allergic rhinitis was 15.4% and 23.3%, respectively; both disease entities tended to occur more frequently in male than in female subjects. The prevalence rate of asthma, atopic dermatitis, and food allergy was 5.2%, 14.1%, and 3.9%, respectively. Our results suggest that the prevalence rates of atopic diseases including Japanese cedar pollinosis are dramatically increasing across all age groups in Japan. In particular, the increasing prevalence rate of Japanese cedar pollinosis seems to reflect higher exposure to the Japanese cedar pollen antigen in many prefectures.     

ADAM33 polymorphisms are associated with asthma susceptibility in a Japanese population

BACKGROUND: Asthma is the most common chronic disorder in childhood, and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Asthma is believed to be a complex disorder involving genetic and environmental factors, and several asthma susceptibility loci have been identified through genome-wide screening. A disintegrin and metalloprotease 33 (ADAM33) was the first asthma susceptibility gene to be discovered by positional cloning in 2002. OBJECTIVE: The aim of the present study was to investigate whether single-nucleotide polymorphisms (SNPs) in ADAM33 are associated with childhood asthma in the Japanese population. METHODS: Twenty-three ADAM33 SNPs were genotyped by fluorescence correlation spectroscopy with the use of DNA from 155 families (538 members) identified through children with atopic asthma. The transmission disequilibrium test (TDT) was performed for family-based association study. RESULTS: TDT revealed that minor alleles of S+1, ST+4, and T2 SNPs were over-transmitted to asthma-affected offspring (P<0.05). According to the haplotype TDT, no haplotype of ADAM33 was transmitted preferentially to asthmatic offspring. CONCLUSION: Our results confirm the involvement of ADAM33 in the development of childhood asthma among the Japanese.     

Polymorphism of the immune-braking gene CTLA-4 (+49) involved in gender discrepancy of serum total IgE levels and allergic diseases

BACKGROUND : A variety of genes are related to allergic disorders in different ethnic populations. The genetic basis for the gender discrepancy of allergic diseases remains to be determined. OBJECTIVE : This study was conducted to investigate whether IL-4 promoter (-590 C/T) and cytotoxic T lymphocyte antigen 4 (CTLA-4) (+49 A/G) polymorphisms were correlated with a gender discrepancy of total IgE levels and allergic diseases in a Chinese population. METHODS : A total of 1333 participants aged 19-49 years were enrolled in this study. Allergic diseases were recognized by the presence of asthma, rhinitis or atopic dermatitis in conjunction with detectable specific IgE in the blood. Polymorphisms of IL-4 promoter (-590) and CTLA-4 (+49) were determined by restriction fragment length polymorphism. RESULTS : Males or females with allergic diseases had higher total IgE levels than those without (P=0.000). Females with the A/A genotype in the CTLA-4 (+49) position had significantly higher total IgE levels than those with A/G, and those with the G/G genotype had the lowest IgE levels (154.9 vs. 107.1 vs. 79.8 KU/L; mean log values: 1.79 vs. 1.65 vs. 1.54, P< 0.001). However, males with different genotypes in the CTLA-4 (+49) position exhibited no difference in the total IgE levels. Females with allergic rhinitis had a significantly higher frequency of the A/A genotype in the CTLA-4 (+49) polymorphism than those without atopic diseases (P=0.016). In contrast, males with and without allergic disorders exhibited no significant difference in the CTLA-4 (+49) polymorphisms (P>0.05). The IL-4 promoter (-590) polymorphisms, however, had no correlation with the total IgE levels or allergic diseases in either females or males. CONCLUSION : In females only, the CTLA-4 (+49), but not the IL-4 promoter (-590), polymorphism was significantly associated with elevation of total IgE levels and allergic rhinitis. Here, we have, for the first time, demonstrated a gender-linked genetic relationship with allergic disease.     

Decrease in the allergenicity of Japanese cedar pollen allergen by treatment with positive and negative cluster ions

BACKGROUND: Japanese cedar pollinosis is a severe allergic disease in Japan. The most effective means of decreasing allergic inflammation reactions is still avoidance of the aeroallergen. Recently, a novel air purification system using positively and negatively charged cluster ions was developed to create comfortable living environments. We aimed to assess the ability of existing technology to lower allergenicity of Japanese cedar pollen. METHODS: A Japanese cedar pollen extract was nebulized from the top of a cylindrical container with 2 or 4 ion-generating devices. The extract in a mist was passed through the space filled with or without plasma cluster ions for 90 s, and the ion-treated or nontreated extract was then collected in a Petri dish at the bottom of the container. RESULTS: The ion-exposed extract was significantly diminished in its reactivities to anti-Cry j 1 or anti-Cry j 2 antiserum and to human allergic sera IgE on ELISA. SDS-PAGE analysis revealed that ion exposure induced protein degradation in the pollen extract. Similarly, the ion treatment impaired about 80% of the binding to pooled sera IgE from patients allergic to Japanese cedar pollen on ELISA inhibition. Furthermore, intracutaneous and conjunctival reaction tests showed a remarkable diminution in the allergenicity of the ion-irradiated extract. CONCLUSION: Ion irradiation resulted in a remarkable decrease in in vitro and in vivo allergenicities of atomized Japanese cedar pollen extracts.     

Association of ADAM33 gene polymorphisms with asthma in Indian children

Asthma is the most common chronic disorder in childhood, and asthma exacerbation is an important cause of childhood morbidity and hospitalization. In the present study, the relationship between single-nucleotide polymorphisms (SNPs) of the ADAM33 gene and asthma in Indian children has been examined using a case-control study. Five SNPs of the ADAM33 gene, F+1(rs511898) G/A, S2 (rs528557) G/C, ST+4 (rs44707) A/C, ST+5 (rs597980) C/T and V4 (rs2787094) C/G, were analyzed in 211 asthma cases and 137 controls aged 1-15 years using the PCR-restriction fragment length polymorphism method. Data were statistically analyzed using the χ(2)-test and logistic regression model. Haplotype estimation and linkage disequilibrium were conducted using the expectation-maximization algorithm. The genotypes and allele frequencies of SNPs S2 and ST+5 of the ADAM33 gene were significantly associated with asthma risk (P = 0.020 - < 0.001), whereas F+1, ST+4, V4 homozygous mutant genotypes and mutant alleles were significantly associated with increased asthma risk (P = 0.031 - < 0.001). A positive association was also found with haplotypes AGCCT, GGACT and AGCCC (P = < 0.001, odds ratio (OR) = 6.10-6.50), whereas ACAGT, AGCGC, AGCGT, GCAGC and GCCGT showed protective association with asthma (P = 0.019-0.000, OR = 0.50-0.20). Taken together, out results suggest that ADAM33 gene polymorphisms may modify individual susceptibility to develop childhood asthma in the Indian population.     

Lowered effectiveness of immunotherapy for cypress pollinosis by using Japanese cedar pollen extract]

BACKGROUND: Japanese cedar and cypress pollen share a common antigen. The cedar pollen season is followed by the cypress pollen season. However, both the clinical significance and involvement of cypress pollinosis in the treatment of the cedar pollinosis have not yet been clarified. METHODS: The clinical efficacy of sublingual immunotherapy with cedar pollen extract for cedar pollinosis was evaluated during the cypress pollen dispersal season in Japan. In addition, the change in cypress pollen specific IgE antibodies of the patients with cedar pollinosis was examined before and after the pollen season. RESULTS: Sublingual immunotherapy with cedar pollen extract did not improve the clinical symptoms of the cedar pollinosis patients combined with cypress pollinosis in the cypress pollen season. The cypress pollen specific IgE antibodies were found to demonstrate significant seasonal changes. CONCLUSION: The presence of cypress pollinosis should therefore be taken into consideration when planning the optimal treatment for cedar pollinosis. Sublingual immunotherapy with cedar pollen extract may not be effective for cypress pollinosis.     

Lack of association between ADAM33 gene and asthma in a Chinese population

Asthma is a complex polygenic disease with gene-environment interactions being important. It has been previously suggested that ADAM33, which is a member of a gene family that encodes membrane-anchored proteins with a disintegrin and a metalloprotease domain, is primarily expressed in lung fibroblasts and bronchial smooth muscle cells and has been associated with airway remodelling and bronchial hyperresponsiveness. A significant association has previously been demonstrated between single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 and asthma in ethnically diverse populations. To assess whether SNPs or haplotypes of ADAM33 are related to asthma in a Chinese Han population, we genotyped three SNPs of ADAM33 (7575G/A in intron 6, 11188A/T in intron 19, and 12433T/C in exon 20) in a case-control study involving 296 patients with asthma and 270 healthy controls. No significant association was detected between these three SNPs and asthma susceptibility in the Chinese population.     

High contribution contrast between the genes of eosinophil peroxidase and IL-4 receptor alpha-chain in Japanese cedar pollinosis

BACKGROUND: Japanese cedar pollinosis is the most common form of hayfever in Japan in spring and has remarkably increased since 1960. OBJECTIVE: We sought to clarify the candidate genes for cedar pollinosis using a case-control study. METHODS: After diagnosing 351 subjects on the basis of an intradermal test, nasal provocation test, and questionnaire regarding nasal and conjunctival symptoms, we determined the blood-specific IgE values and genotypes of eosinophil peroxidase (EPO) and interleukin-4 receptor alpha-chain (IL4RA) in 145 patients with pollinosis and 206 healthy subjects, including 75 healthy subjects with higher specific IgE values. RESULTS: We found significant differences in the frequencies of Pro358Leu in EPO and of Ile50Val and Glu375Ala in IL4RA between patients and healthy subjects. There was a significantly higher frequency of 358Leu in EPO in patients than in healthy subjects showing a higher specific IgE value. In contrast, we recognized significant changes in the prevalence of Ile50Val and Glu375Ala in IL4RA in healthy subjects with a normal IgE value compared with those in healthy subjects with a higher specific IgE value. The relationship between EPO polymorphisms and the onset of symptoms was exactly opposite that for IL4RA. CONCLUSIONS: These results suggest that Pro358Leu in EPO is strongly involved in the development of cedar pollinosis. Ile50Val and Glu375Ala in IL4RA seem to be related to cedar pollen sensitization. Subjects with Ile50 or Glu375 might develop cedar pollinosis with increased exposure to cedar pollen.     

A study of aggravation of atopic dermatitis during Japanese cedar pollen season--correlation with grades of dermatitis on face and Cry j 1 specific IgE]

We studied influence of Japanese cedar pollen (Jcp) on aggravation of atopic dermatitis (AD) during the pollination season. 48.5% of 97 patients with atopic dermatitis showed aggravation of dermatitis during the pollination season and 85% of them had Japanese cedar pollinosis, whereas only 44% of AD patients without the aggravation had the pollinosis. There was no difference of grades of dermatitis on face between the groups with or without the aggravation. Furthermore, we measured specific IgE to Jcp and Cry j 1, a major allergen of Jcp, by ELISA in the sera from the 54 patients with AD. The levels of specific IgE antibodies to both allergens in the group with the pollinosis were significantly higher than in the group without the pollinosis. However, significant difference of those was not recognized between the groups with or without the aggravation of AD. Therefore, our study has suggested that Japanese cedar pollen is likely to be one of causes of seasonal aggravation of AD in individuals sensitized to the pollen, and some other factors, e.g. Jcp-specific T cells, might play an important roll in addition to the Jcp-specific IgE.     

Preclinical evaluation of an immunotherapeutic peptide comprising 7 T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens.

BACKGROUND: Peptide immunotherapy is a new approach to treating allergic diseases, but a therapeutic peptide for Japanese cedar pollinosis has not yet been developed. OBJECTIVE: The aim of this study is to prepare and preclinically evaluate a hybrid peptide comprising 7 T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens. METHODS: The recombinant hybrid peptide was prepared after immunodominance of 7 T-cell determinants was confirmed by means of PBMC proliferation assay in 113 volunteers with pollinosis. The hybrid peptide was compared with a mixture of the 7 T-cell determinants in a dose-dependent PBMC proliferation assay in 6 volunteers with pollinosis. PBMC proliferation and binding activity of serum IgE antibody against the hybrid peptide, Cry j 1, and Cry j 2 were investigated in 48 volunteers with pollinosis. RESULTS: The hybrid peptide induced T-cell proliferation with an average 100-fold lower concentration than a mixture of the 7 peptides. PBMCs from 44 (92%) of 48 volunteers proliferated against the hybrid peptide, with significant correlation (r = 0.87) in T-cell proliferation against Cry j 1 and Cry j 2. No serum IgE antibodies specific to Cry j 1 or Cry j 2 bound to the hybrid peptide. CONCLUSION: A hybrid peptide comprising 7 T-cell determinants has the potential for inducing T-cell proliferative responses that is superior to the potential of a mixture of the T-cell determinants and comparable with that of Cry j 1 and Cry j 2. The hybrid peptide will be of use in specific immunotherapy against Japanese cedar pollinosis.     

A comprehensive evaluation of IL4 variants in ethnically diverse populations: association of total serum IgE levels and asthma in white subjects

BACKGROUND: The role of variation in the IL4 gene in asthma and allergy susceptibility is controversial. This cytokine is important in IgE isotype switching and the regulation of allergic inflammation; however, published studies have not delineated the specific role of variation in this gene in allergic disorders. OBJECTIVE: We sought to identify single nucleotide polymorphisms (SNPs) in IL4 and to evaluate the association of SNPs and haplotypes with asthma and allergic phenotypes (total serum IgE) in white, African American, and Hispanic asthmatic populations. METHODS: Sixteen individuals were resequenced, and 19 SNPs were identified; 2 novel and 17 SNPs were previously reported. Eleven of the SNPs were used to evaluate association in the 3 groups. RESULTS: Nine polymorphisms were associated with total serum IgE levels in white subjects (.0012 < or = P < or =.034), and 5 of these were also associated with asthma in this population (.010 < or = P < or =.031). Three common haplotypes were observed, and all were associated with either high or low serum IgE levels in white subjects (.00008 < or = P < or =.004). Inspection of the haplotypes revealed that 3017 G/T in intron 2 was the only SNP concordant with serum IgE levels (G allele with lower levels and T allele with higher levels). CONCLUSIONS: After a comprehensive genetic evaluation, our data suggest that the 3017 G/T variant or the haplotype it identifies influences IL4's ability to modulate total serum IgE levels. Inconsistencies with previously reported IL4 associations might be due to population differences in allele frequencies, the extent of linkage disequilibrium with this SNP or haplotype, or both.