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Shingo Ochiai,
Naoki Shimojo,
Yoshinori Morita,
Minako Tomiita, Takayasu Arima,
Yuzaburo Inoue,
Mayuko Nakaya,
Naoki Uehara,
Yasunori Sato,
Chisato Mori,
Yoichi Suzuki,
Yoichi Kohno
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ABSTRACT: Background: A few studies have reported that the quantity of selected cytokines/chemokines in breast milk might be associated with atopic dermatitis (AD). Using the multiplex cytokine assay system, we examined cytokines/chemokines in human milk in order to identify new biomarkers related to AD. Methods: We recruited 49 infants with or without AD who participated in a birth cohort and measured the concentrations of cytokines/chemokines in the colostrum (collected within 4-5 days after birth) and mature milk (collected at 1 month postpartum) received by the infants. Results: There were significant differences in the concentrations of interleukin (IL)-1β and IL-12p40 in the colostrum, and in those of IL-4, eotaxin, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α2 and MIP-1α in the mature milk between the milk received by infants who developed AD at the age of 6 months and that received by the control infants. There was weak to moderate correlation between those 6 cytokines/chemokines in mature milk. Atopic history and IgE levels of mothers were not related to cytokine/chemokine concentrations in breast milk. Logistic regression analyses showed that high levels of eotaxin in the mature milk were a risk for the development of AD at 6 months of age. Conclusion: These results suggest that several cytokines/chemokines, especially eotaxin, are potential biomarkers for development of AD in early infancy.
International Archives of Allergy and Immunology 11/2012; 160(4):401-408. · 2.40 Impact Factor
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Fumiya Yamaide,
Siizkhuu Undarmaa,
Yoichi Mashimo,
Naoki Shimojo, Takayasu Arima,
Yoshinori Morita,
Tomomitsu Hirota,
Kimie Fujita,
Akihiko Miyatake,
Satoru Doi, [......],
Hiroko Watanabe,
Akira Hoshioka,
Minako Tomiita,
Akiko Yamaide,
Misa Watanabe,
Yoshitaka Okamoto,
Yoichi Kohno,
Mayumi Tamari,
Akira Hata,
Yoichi Suzuki
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ABSTRACT: Background: Matrix metalloproteinase 12 gene (MMP12) has been shown to be associated with asthma in a Caucasian population. In this study, we investigate whether single-nucleotide polymorphisms (SNPs) of MMP12 are associated with a risk for asthma in a Japanese population. Methods: We tested for an association between SNPs in MMP12 and asthma, including its severity, in a Japanese population (630 pediatric and 417 adult patients with atopic asthma and 336 children and 632 adults as controls). The rs652438 A and G variants (N357S) were generated by site-directed mutagenesis and an assay with artificial peptide substrates was used to compare two types of MMP12 activity. The effect of MMP12 inhibition with MMP12-specific small interfering RNA (siRNA) on chemokine secretion from airway epithelial cells was also tested in vitro. Results: N357S showed a p value <0.05 for childhood and combined (adult plus childhood) asthma in the dominant model [odds ratio (OR) 1.60, 95% confidence interval (CI) 1.00-2.56, p = 0.047; OR 1.40, 95% CI 1.04-1.89, p = 0.028, respectively]. This risk variant is associated with asthma severity in adult patients. In the functional assay, the minor-allele enzyme showed significantly lower activity than the major-allele enzyme. MMP12-specific siRNA suppressed IP-10 secretion from airway epithelial cells upon stimulation with IFN-β. Conclusions: Our results suggest that MMP12 confers susceptibility to asthma and is associated with asthma severity in a Japanese population. MMP12 may be associated with asthma through inappropriate attraction of leukocytes to the inflamed tissue.
International Archives of Allergy and Immunology 10/2012; 160(3):287-296. · 2.40 Impact Factor
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ABSTRACT: Blau syndrome/early-onset sarcoidosis (Blau/EOS) is an autoinflammatory disease characterized by granulomatous arthritis, uveitis, and skin rash. It has been shown that gain-of-function NOD2 mutations cause Blau/EOS. In this paper, we describe a patient with a gain-of-function NOD2 mutation who developed infantile Takayasu arteritis, which is rare in Blau/EOS, but who has not yet had significant granulomatous changes in joints, eyes, or skin. We suspect that this case is an unusual phenotype of Blau/EOS.
Modern Rheumatology 07/2012; · 1.58 Impact Factor
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Syuji Yonekura,
Yoshitaka Okamoto,
Naoki Shimojo,
Heizaburo Yamamoto,
Daiju Sakurai,
Shigetoshi Horiguchi,
Toyoyuki Hanazawa,
Yuzaburo Inoue, Takayasu Arima,
Minako Tomiita,
Yoichi Kohno
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ABSTRACT: This preliminary prospective study suggests that background factors may differ among allergic diseases. The beneficial interventions for reducing development of allergic rhinitis (AR) are also effective for the prevention of subsequent onset of bronchial asthma (BA).
To determine the risk factors associated with onset of AR in atopic children in a prospective study.
All patients with atopic dermatitis (AD) or food allergy with or without BA who visited the Pediatric Unit of Chiba University Hospital from 2005 to 2006 were enrolled in the study and received allergy examinations every 3-6 months.
A total of 100 patients were followed up for more than 2 years. Among the 60 patients without BA at entry to the study, 12 developed BA during the follow-up period. Development of AR preceded BA in 10 of the 12 patients (83.3%). In the background factors at the entry, positive sensitization to house dust mite (HDM) was significantly related to development of BA. Among the 48 patients without AR, 20 developed AR. High titers of serum HDM-specific IgE and high eosinophil counts in blood, and detection of eosinophils in nasal smears at the entry were significantly related to development of AR.
Acta oto-laryngologica 04/2012; 132(9):981-7. · 0.98 Impact Factor
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ABSTRACT: The objective of this study was to analyze the sensitization to casein and beta-lactoglobulin (BLG) in children with cow's milk allergy (CMA) in Japan. To this end, 115 CMA children were selected on the basis of the presence of cow's milk-specific IgE antibodies in serum and compatible clinical history. Specific IgE antibodies against casein and BLG were determined using CAP-RAST (considered positive when score 2 or more).
Titer of anti-casein IgE was significantly higher than that of anti-BLG IgE in CMA patients. IgE antibodies specific to casein were positive in 107 patients (97.3%), while those to BLG were positive in 51 patients (46.6%). Forty-eight patients (43.6%) were positive to both casein and BLG. We divided patients to two groups who were sensitized to casein only (C group) and who were sensitized to both casein and BLG (C/B group). No significant difference was seen in sensitization rate to white egg between C/B group and C group. However titer of anti-white egg IgE was significantly higher in C/B group than C group. As for sensitization rate and levels of specific antibodies to mite and Japanese cedar pollen there was no difference between two groups. Rates of resolution of CMA at the 3 years of age were higher in the C group than C/B group.
In conclusion we found that casein is a major allergen of cow's milk allergy in Japanese children. Patients who are sensitized to several milk allergens are likely to be more sensitized to other food allergens. Sensitization to several milk allergens tends to have poor prognosis of CMA.
Arerugī = [Allergy] 02/2010; 59(2):117-22.
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ABSTRACT: Our objective was to investigate the efficacy of intravenous alendronate for the treatment of glucocorticoid-induced osteoporosis (GIOP) in children with autoimmune diseases. Five children with autoimmune disease and GIOP were treated with 5 mg intravenous alendronate once every 3 months. After 1 and 2 years, we evaluated the changes in the Z score of the femoral neck bone mineral density (BMD), serum bone alkaline phosphatase, and urinary deoxypyridinoline. Six patients with GIOP, whose BMD could be observed over a 1-year period without alendronate treatment, were defined as controls. After 1 and 2 years of treatment, intravenous treatment significantly inhibited bone loss. The efficacy of alendronate demonstrated a significant correlation with a high level of bone turnover markers before alendronate treatment. Intravenous alendronate is considered to be a good choice for the treatment of GIOP because of its excellent efficacy. In addition, our study suggests that the efficacy of alendronate depends on the bone turnover of patients before treatment. Intervention with bisphosphonates during periods of high bone turnover may be recommended.
Clinical Rheumatology 08/2008; 27(7):909-12. · 2.00 Impact Factor
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ABSTRACT: We previously showed that immunization of mice with murine fibroblasts transfected with the thyrotropin receptor (TSHR) and a murine major histocompatibility complex (MHC) class II molecule induces immune thyroid disease with the humoral and histological features of human Graves' disease in about 20% of mice. In this model, based on the proliferative response of T cells from hyperthyroid mice to a panel of overlapping TSHR peptides, we now demonstrate that TSHR 121-140 peptide contains an immunodominant T cell epitope. Supporting this conclusion, spleen cells from mice immunized with TSHR 121-140 peptide showed a strong proliferative response to fibroblasts transfected with the TSHR and a murine I-A(k) molecule, but not either alone. Also, intranasal administration of 100 mug of TSHR 121-140 peptide led to suppressed proliferative response of lymph node cells to the peptide. Interestingly, however, administration of this peptide enhanced, rather than suppressed, the frequency and severity of Graves' disease induced by the immunization of the fibroblasts transfected with the TSHR and a murine I-A(k) molecule. Spleen cells from hyperthyroid mice that were pretreated with intranasal peptide tended to produce lesser amounts of IL-4, IL-10 and IFN-gamma than those from normothyroid control mice. Although precise mechanisms of this enhancement remain to be determined, the results suggest that attempts to treat Graves' disease by intranasal administration of an immunodominant TSHR T cell epitope may aggravate, not prevent, the disease.
Clinical Immunology 05/2008; 127(1):7-13. · 4.05 Impact Factor
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Eduardo Jose Campos Alberto,
Naoki Shimojo,
Yoichi Suzuki,
Yoichi Mashimo, Takayasu Arima,
Tomoko Matsuura,
Yuzaburo Inoue,
Akiko Yamaide,
Minako Tomiita,
Katsunori Fujii,
Akira Hata,
Yoichi Kohno
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ABSTRACT: The regulatory IL-10 and TGF-beta1 cytokine gene polymorphisms have been associated with allergic diseases in different populations, like Caucasian, Chinese and Indians. We investigated the association between the polymorphisms IL-10 A-1082G, C-819T, C-627A and TGF-beta1 T+869C, G+915C, C-509T and food allergy in Japanese children. One hundred and eleven children with food allergy and 115 atopic control children without food allergy were recruited. DNA samples from these subjects were genotyped by using PCR. The odds ratio of IL-10 -1082 AA genotype was 2.5 (95% CI, 1.0-6.4) for food allergy risk when compared with atopic control subjects (p = 0.03). There were no significative differences in the frequency of TGF-beta1 gene polymorphisms between both groups. Our results indicate that IL-10 A-1082G gene polymorphism is associated with food allergy susceptibility in atopic Japanese children.
Pediatric Allergy and Immunology 02/2008; 19(8):716-21. · 2.46 Impact Factor
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ABSTRACT: Cogan's syndrome is a rare inflammatory disease characterized by nonsyphilitic ocular interstitial keratitis associated with hearing loss and vestibular impairment. Although systemic corticosteroids are usually used as the standard therapy, hearing ability in most cases gradually deteriorates. We, herein, describe a patient with childhood Cogan's syndrome who was treated with low-dose oral methotrexate, which successfully helped to taper the doses of the systemic corticosteroids. The serum levels of the complements were good markers for the disease activity in this patient.
Clinical Rheumatology 01/2008; 26(12):2201-3. · 2.00 Impact Factor
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ABSTRACT: Cogan’s syndrome is a rare inflammatory disease characterized by nonsyphilitic ocular interstitial keratitis associated with
hearing loss and vestibular impairment. Although systemic corticosteroids are usually used as the standard therapy, hearing
ability in most cases gradually deteriorates. We, herein, describe a patient with childhood Cogan’s syndrome who was treated
with low-dose oral methotrexate, which successfully helped to taper the doses of the systemic corticosteroids. The serum levels
of the complements were good markers for the disease activity in this patient.
Clinical Rheumatology 11/2007; 26(12):2201-2203. · 2.00 Impact Factor
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World Allergy Organization Journal 10/2007;
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Yuzaburo Inoue,
Naoki Shimojo,
Yoichi Suzuki,
Eduardo Jose Campos Alberto,
Akiko Yamaide,
Shuichi Suzuki, Takayasu Arima,
Tomoko Matsuura,
Minako Tomiita,
Masahiko Aoyagi,
Akira Hoshioka,
Akihito Honda,
Akira Hata,
Yoichi Kohno
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ABSTRACT: The contribution that genetic polymorphisms of Toll-like receptor (TLR) 4 and of CD14--both of which recognize respiratory syncytial virus (RSV) in the innate immune response--make to RSV bronchiolitis in the Japanese population has not yet been clarified.
This study genotyped 2 TLR4 mutations, Asp299Gly and Thr399Ile, and 2 single-nucleotide polymorphisms (SNPs) of CD14, -550 C/T and -159 C/T, in 54 children with RSV bronchiolitis and in 203 control subjects. CD14 SNPs and the serum level of soluble CD14 (sCD14) also were examined in 67 cord-blood specimens and in serum samples from 73 6-year-old children.
No TLR4 mutations were found. The frequencies of both the CC genotype and the C allele of CD14 -550 C/T were significantly higher in children with RSV bronchiolitis than in the control subjects. The serum level of sCD14 was significantly higher in children with the CC genotype of CD14 -550 C/T than in those with the CT and TT genotypes.
CD14 -550 C/T, which is related to the serum level of sCD14, is associated with the development of RSV bronchiolitis in the Japanese population. This study's results indicate that, in different ethnic groups, different genetic factors contribute to the development of RSV bronchiolitis.
The Journal of Infectious Diseases 07/2007; 195(11):1618-24. · 6.41 Impact Factor
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Eduardo Campos,
Naoki Shimojo,
Yuzaburo Inoue, Takayasu Arima,
Shuichi Suzuki,
Minako Tomiita,
Tomoko Matsuura,
Akira Hata,
Yoichi Suzuki,
Masahiko Aoyagi,
Yoichi Kohno
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ABSTRACT: The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localized on chromosome 5q31, a region that is linked to atopy-related phenotypes. Although it has been shown that a polymorphism in the 5' region of the CD14 gene is associated with food allergy in white subjects, it is not clear whether this association is also present in the Japanese population.
Eighty-eight children with food allergy were recruited along with 101 children controls without food allergy. DNA samples from these subjects were genotyped by PCR-based restriction fragment length polymorphism (RFLP) assay to investigate the relationship between two polymorphisms in the 5' region of the CD14 gene (C-159T and C-550T) and food allergy.
There was no association among the CD14 alleles, dominant model or recessive model of either polymorphism with food allergy.
The CD14-159 and -550 polymorphisms might not play a major role in the pathogenesis of food allergy in Japanese children.
Allergology International 04/2007; 56(1):23-7.
