아토피피부염에서 초항원의 역할

홍수종 대한알레르기학회 1999 천식 및 알레르기 Vol.19 No.5

Association Between Serum IgE Levels and the CTLA4 +49A/G and FCER1B -654C/T Polymorphisms in Korean Children With Asthma

홍수종,오규영,강미진,최원아,권지원,김병주,유진호 대한천식알레르기학회 2010 Allergy, Asthma & Immunology Research Vol.2 No.2

Purpose: T cells play a central role in cell-mediated immunity, atopic disease, and asthma. The balance of CD28/cytotoxic T-lymphocyte antigen 4(CTLA4)-derived signal transduction plays an important role in the activation of T cells and an increased immunoglobulin E (IgE) response. The aim of the current study was to investigate the association between polymorphisms in the genes encoding both CTLA4 and the high-affinity IgE receptor 1B (FCER1B) and serum IgE levels in Korean children with asthma. Methods: We enrolled 238 controls and 742 children with asthma. The CTLA4 +49A/G and FCER1B -654C/T polymorphisms were genotyped by PCR-restriction fragment length polymorphism analysis. Results: We observed no difference in the distribution of CTLA4 +49A/G among controls, children with asthma, and those with atopic asthma. In contrast, the GA genotype of CTLA4 +49A/G in children with atopic asthma was significantly higher compared to that in those with non-atopic asthma. Moreover, significantly higher log Dp/Df-specific IgE levels were found in children with asthma and those with atopic asthma carrying one or two copies of the CTLA4 +49A versus those homozygous for +49G. Gene-gene interactions between CTLA4 and FCER1B with the heterozygote and homozygote of variant genotypes were associated with the log Dp/Df-specific IgE levels, but not asthma development. In addition, children with Dp/Df (+)asthma carried an elevated combined genotype of risk allele compared to those with Dp/Df (-) asthma. Conclusions: The CTLA4 +49A/G polymorphism may contribute to the production of IgE in Korean children with asthma, especially in Dp/Df-specific IgE levels, but not in the direct development of asthma. In addition, Dp/Df-specific IgE levels with a FCER1B -654C/T polymorphism may involve additive effects.

Bronchiolitis Obliterans의 임상적 특징과 진단 그리고 대책

홍수종 대한 소아알레르기 및 호흡기학회 2000 소아알레르기 및 호흡기학회지 Vol.10 No.부록1

The Effects of Lactobacillus rhamnosus on the Prevention of Asthma in a Murine Model

홍수종,유진호,장성옥,김병주,송영화,권지원,강미진,최원아,정현돈 대한천식알레르기학회 2010 Allergy, Asthma & Immunology Research Vol.2 No.3

Purpose: Lactobacilli are probiotic bacteria that are effective in the management of allergic diseases or gastroenteritis. It is hypothesized that such probiotics have immunoregulatory properties and promote mucosal tolerance. Our goal was to investigate whether Lactobacillus casei rhamnosus Lcr35 could inhibit airway inflammation in an ovalbumin (OVA)-induced murine model of asthma. Methods: BALB/c mice aged 6 weeks were used in the present study. Lactobacillus casei rhamnosus Lcr35 was administered daily, starting 1 week prior to the first OVA sensitization (group 1) and 2days before the first 1% OVA airway challenge (group 2). Mice that received only saline at both sensitization and airway challenge time points were used as negative controls (group 3), and those that had OVA-induced asthma were used as positive controls (group 4). Airway responsiveness to methacholine was assessed, and bronchoalveolar lavage (BAL) was performed. At the endpoint of the study, total IgE as well as OVA-specific IgE,IgG1 and IgG2a in serum was measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: Airway hyperresponsiveness,total cell counts and the proportion of eosinophils in BAL fluid were significantly decreased in group 1 compared with group 4 (P<0.05). Total serum IgE levels were also significantly decreased in group 1 compared with group 4. Serum levels of OVA-specific IgE, IgG1 and IgG2a were not significantly influenced by treatment with Lcr35. There was significantly less peribronchial and perivascular infiltration of inflammatory cells in group 1 compared with group 4; however, there were no significant differences in methacholine challenge, BAL, serology or histology between groups 2and 4. Conclusions: Oral treatment with Lcr35 prior to sensitization can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. These results suggest that Lcr35 may have potential for preventing asthma.

한국 소아알레르기 질환의 유병률

홍수종,이수영,김규언 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.4

Asthma and allergic diseases are one of the most common disorders in children. Due to its increased prevalence, as well as the increased morbidity and mortality from these diseases, asthma and allergic diseases have come to be recognized as a major worldwide public health issue. In addition, socioeconomic burden of asthma and allergic diseases has increased in Korea also. The International Study of Asthma and Allergies in Childhood (ISAAC) investigated the worldwide prevalence of asthma and other allergic diseases using simple standardized methods because of the comparison of asthma and allergic diseases between the countries. In Korea, several epidemiologic studies have been conducted to determine the prevalence of asthma in children. Although these studies showed increased prevalence of asthma among Korean children (from 3.4% in 1964 to 10.1% in 1989), these findings were based on data from small numbers of subjects. The first Nationwide Study of Asthma and Allergies in Korean Children, which utilized the Korean version of ISAAC written and video questionnaire, was conducted in 1995 and the second Nationwide Study of Asthma and Allergies in Korean Children was conducted in 2000, directed by the Korean Academy of Pediatric Allergy and Respiratory Diseases. We report here the prevalence of asthma and other allergic diseases in Korean children and adolescents, and show the changes that occurred over this 5 year period. We also describe the risk factors for development of these diseases in Korean children. We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 25,117 children selected from 34 elementary school and 14,946 children selected from 34 middle school across the nation, the response rate was 94.8%. In 2000, 27,831 children selected from 34 elementary school and 15,214 children selected from 34 middle school, and the response rate was 96.4%. From these studies, we can confirm that increase of the prevalences of asthma, allergic rhinitis, and atopic dermatitis in Korea, except the prevalence of food allergy. Especially, the video questionnaire showed increases in the lifetime and 12 month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time in middle school children. In addition, the increase of prevalences of symptoms, diagnosis and treatment of atopic dermatitis was noted significantly. Risk factor analysis showed that body mass index (BMI), passive smoking and living with a dog or cat were associated with higher risk of wheeze. Also the occurrence of fever during infancy and the frequent use of antibiotics were associated with the risk of wheeze. In conclusion, during the 5 year period from 1995 to 2000, the prevalences of asthma, allergic rhinitis, and atopic dermatitis has increased in Korean children. BMI, passive smoking, living with a dog or cat, the fever episodes in infancy, and the frequent use of antibiotics in infancy are important risk factors to development of asthma and atopic dermatitis. In the near future, the birth cohort study will be needed to investigate the causes of this increase and the natural course of allergic diseases, then we develop the methods to control asthma and allergic diseases. (Korean J Pediatr 2008;51:343-350) Asthma and allergic diseases are one of the most common disorders in children. Due to its increased prevalence, as well as the increased morbidity and mortality from these diseases, asthma and allergic diseases have come to be recognized as a major worldwide public health issue. In addition, socioeconomic burden of asthma and allergic diseases has increased in Korea also. The International Study of Asthma and Allergies in Childhood (ISAAC) investigated the worldwide prevalence of asthma and other allergic diseases using simple standardized methods because of the comparison of asthma and allergic diseases between the countries. In Korea, several epidemiologic studies have been conducted to determine the prevalence of asthma in children. Although these studies showed increased prevalence of asthma among Korean children (from 3.4% in 1964 to 10.1% in 1989), these findings were based on data from small numbers of subjects. The first Nationwide Study of Asthma and Allergies in Korean Children, which utilized the Korean version of ISAAC written and video questionnaire, was conducted in 1995 and the second Nationwide Study of Asthma and Allergies in Korean Children was conducted in 2000, directed by the Korean Academy of Pediatric Allergy and Respiratory Diseases. We report here the prevalence of asthma and other allergic diseases in Korean children and adolescents, and show the changes that occurred over this 5 year period. We also describe the risk factors for development of these diseases in Korean children. We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 25,117 children selected from 34 elementary school and 14,946 children selected from 34 middle school across the nation, the response rate was 94.8%. In 2000, 27,831 children selected from 34 elementary school and 15,214 children selected from 34 middle school, and the response rate was 96.4%. From these studies, we can confirm that increase of the prevalences of asthma, allergic rhinitis, and atopic dermatitis in Korea, except the prevalence of food allergy. Especially, the video questionnaire showed increases in the lifetime and 12 month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time in middle school children. In addition, the increase of prevalences of symptoms, diagnosis and treatment of atopic dermatitis was noted significantly. Risk factor analysis showed that body mass index (BMI), passive smoking and living with a dog or cat were associated with higher risk of wheeze. Also the occurrence of fever during infancy and the frequent use of antibiotics were associated with the risk of wheeze. In conclusion, during the 5 year period from 1995 to 2000, the prevalences of asthma, allergic rhinitis, and atopic dermatitis has increased in Korean children. BMI, passive smoking, living with a dog or cat, the fever episodes in infancy, and the frequent use of antibiotics in infancy are important risk factors to development of asthma and atopic dermatitis. In the near future, the birth cohort study will be needed to investigate the causes of this increase and the natural course of allergic diseases, then we develop the methods to control asthma and allergic diseases. (Korean J Pediatr 2008;51:343-350)

류마티열

洪秀宗 임상약학사 1992 臨床藥學 Vol.12 No.9

소아에서 우중엽 증후군

홍수종,이소연 대한 소아알레르기 호흡기학회 2004 Allergy Asthma & Respiratory Disease Vol.14 No.4

천식환아와 정상아에서 β2-아드레날린 수용체 유전자 다형에 관한 연구

홍수종,김봉성,김자형,오홍범,이무송,최수옥,김미영,오선영,박양,고영률 대한 소아알레르기 호흡기학회 2002 Allergy Asthma & Respiratory Disease Vol.12 No.4

목 적 : 천식의 치료에 있어서 염증조절제의 역할이 강조되고 있기는 하지만, 아직 β2-아드레날린 수용체와 반응하여 기도 수축을 이완시키는 β2-항진제의 역할은 중요하다. 근래에 β2-아드레날린 수용체 유전자 다형과 관련하여, Gly16과 중증 천식 및 야간 천식과 관련이 있고, Glu27은 천식에서 기도과민성의 감소와 관련이 있으며, Gly16 Gln27 일배체형은 아토피군에서 야간 기침과 관련이 있다고 보고되었다. 본 연구에서 천식환자와 정상군에서 β2-아드레날린 수용체 유전자 다형이 차이가 있는지 확인하고, β2-아드레날린 수용체 유전자가 아토피지표 및 기도과민성과 연관성이 있는지 조사하였다.방 법 : 천식으로 진단된 99명과 아토피가 없는 정상아 73명을 대상으로, 말초혈액내 총 호산구수와 혈청 총 IgE를 측정하였고, 메타콜린 기관지 유발검사 및 폐기능검사를 실시하였다. β2-아드레날린 수용체 유전자의 일배체형 분석을 위해 아미노산 16과 27의 부위를 포함하고 있는 β2-아드레날린 수용체의 유전자부위를 polymerase chain reaction(PCR)으로 증폭한 후 16번 유전형은 allele specific PCR, 27번 유전형은 PCR-restriction fragment length polymorphism(RFLP) 방법으로 분석하였다.결 과 : β2-아드레날린 수용체의 16번과 27번 대립 유전자의 빈도는 두 군 사이에 차이가 없었으며, 16번과 27번 아미노산의 일배체형 빈도도 두 군 사이에 차이가 없었다. 그러나 Arg16 Glu27은 한 례도 없어 Arg16은 Gln27과 강한 연쇄불평형이 관찰되었다. 천식군에서 총호산구수와 호산구 분율(%) 및 총 IgE 농도는 각각의 일배체형에 따라 차이가 없었으며, PC20 및 기도 자극 후 β2-항진제에 대한 반응 수치도 각각 일배체형에 따라 차이가 없었다. β2-adrenoceptor Polymorphisms between Asthmatic and Normal Children in KoreaSoo-Jong Hong, M.D.1, Bong-Seong Kim, M.D.1, Ja-Hung Kim, M.D.1,Heung-Bum Oh, M.D.2, Moo-Song Lee, M.D.3, Soo-Ok Choi, M.D.4,Mi-Young Kim, M.D.4, Sun-Young Oh, M.D.5, Yang Park, M.D.6, Young-Yull Koh, M.D.6

천식 환아 말초혈액 단핵구의 싸이토카인 생산 양상

홍수종,심정연,조유숙,박재경,우빈,문희범 대한천식알레르기학회 1997 천식 및 알레르기 Vol.17 No.3

To investigate the imbalance of the cytokine production profile of T cells from atopic asthmatics, we measured concentrations of IL - 4, IL - 5 and IFN-r by ELISA method in the culture supernatants of peripheral blood mononuclear cells(PBMCs) and Dermato- phagoides pteronyssinus(Der p) 1 stimulated PBMCs from Der p sensitized atopic asthmatics, Der p sensitized.healthy atopics, non atopic asthmatics and healthy non atopics. The suppressive effect of IFN-r on cytokine production of Der p 1 stimulated PBMCs was also examined. The PBMCs from atopics showed higher IL 4 and IL 5 production in response to PHA +TPA and higher IFN-r production in response to Der p lq compared with non atopics. The Der p 1 stimulated PBMCs from atopics showed a tendency of increased IL 5 production in response to Der p 1 and higher IL 4 and IL 5 production in response to PHA+TPA compared with non atopics. IL 5 production of Der p 1 stimulated PBMCs from atopics was suppressed by IFN - r It is suggested t,hat an imbalance in IL 4, IL 5 and IFN -r production is a feature of the atopic state. The TH characteristics of allergen stimulated PBMCs could be regulated by IFN -r .

천식 환자에서 분리된 Dermatophagoides pteronyssinus 항원 - 특이 T세포 클론의 특성

홍수종,오순환,조영주,유빈,고윤석,문희범 대한천식알레르기학회 1995 천식 및 알레르기 Vol.15 No.1

T cells play a central role in IgE synthesis and airway inflammation in asthmatic patients. In order to characterize antigen specific T cell clones, we established Dermatophagoides pteronyssinus(D.p) specific and purified protein de- rivatives(PPD) -specific T cell clones, and investigated their cytokine production profile in response to the antigenic and nonspecific stimulation. We established six D.p-specific T cell clones from the peripheral blood of two atopic asthmatics and seven PPD-specific T cell clones from one PPD sensitized ayrnptomatic individual and two pulmonary tuberculosis pa- tients using limiting dilution method. We analyzed the ability of T cell clones to produce IL 4, IFNy and their IL 2R expres- sion upon stimulation with D.p, PPD or PHA plus TPA. Only one D.p-specific T cell clone produced IL 4 upon stimulation with D.p, whereas three clones produced both IL 4 and IFNy upon stimulation with PHA plus TPA, Four PPD specific T cell clones produced IFNy upon stimulation with PPD, five clones produced IFNy upon stimulation with PHA plus TPA, but none of them produced IL-4 regardless of stimulation. Two of five D.p-specific T cell clones and one of four PPD-specific T cell clones showed more than 200 % increass in IL 2R expression upon stimulation with each antigen. These data showed that some of D.p-specific T cell clones were able to produce both IL 4 and IFNy after nonspecific stimulation, but PPD specific T cell clones produced only IFNy regardless of stimulation. This suggests that D. p-specific T cell clones have the ability to produce TH, type cytokines depending on the stimulation.