학동전기 천식환자에서 혈청 총 IgE와 항원감작 및 기관지과민성과의 관계

전재성 ( Jae Sung Jun ),윤기태 ( Ki Tae Yun ),강임주 ( Im Ju Kang ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2009 소아알레르기 및 호흡기학회지 Vol.19 No.3

서론: 천식환자에서 IgE의 증가는 폐기능 및 기관지과민성과 관련이 있고 특히 항원 감작정도가 IgE의 증가에 상당한 영향을 미친다. 따라서 저자들은 학동전기 소아 천식환자에서 혈청 IgE의 증가와 항원감작 및 기관지과민성과의 관계를 알고자 본 연구를 실시하였다. 대상: 최근 3년간 대구파티마병원 소아청소년과 외래를 방문한 4-6세 사이의 천식 환자 중 알레르기 검사와 함께 메타콜린 흡입 후 흉부청진 즉, Provocative concentration at wheezing (PCw) 및 산소포화도 측정 Provocative concentration at 5% fall of oxygen saturation (PCsat)을 이용한 기관지과민성 검사가 가능했던 환아 109명을 혈청 IgE가 120 IU/mL 미만인 IgE 비증가군 (38명), 120-1,000 IU/mL인 중등도증가군과(45명), 1,000 IU/mL 이상의 고증가군 (26명)으로 분류하여 IgE와 천식병력, 항원 감작, 천식의 중증도 및 기관지과민성과의 관계를 비교하였다. 결과: 가족의 천식병력, 영아기의 모유수유, 집안의 애완동물, 간접흡연이 IgE의 증가와 관련이 없었으나(P>0.050, P=0.631, P=0.066, P=0.056), 아토피피부염의 동반과 함께 혈중 호산구 및 ECP의 증가는 IgE의 증가와 관련이 있었다.(P=0.003, P=0.000, P=0.011) 천식의 중증도와 함께 기관지 과민성의 증가는 IgE의 증가와 관련이 없었으나, 음식항원, 흡입항원, 음식 및 흡입항원 동시 감작의 빈도는 IgE 증가시 감작 빈도가 유의하게 높았다.(P=0.000, P=0.000, P=0.000) IgE 고증가군의 위험요인으로 450/mm3 이상의 혈중 호산구, 아토피피부염의 동반, 음식항원 감작, 흡입항원 감작의 Odds ratio (95% Confidence interval)가 각각 3.2 (1.2-9.2), 4.4 (1.7-11.2), 4.8 (1.7-13.2), 5.5 (1.2-24.9)로 의미 있게 나타났다. 결론: 학동전기 소아천식환자에서 IgE의 중등도 증가는 항원감작과 및 기관지과민성과 상당한 관련이 있으나, 고증가군은 항원감작과 함께 다른 요인이 관여할 것으로 생각되며 향후 좀 더 많은 연구가 필요할 것으로 생각된다. Purpose: This study aimed to evaluate the relationship between the serum IgE level and allergic sensitization/bronchial hyperresponsiveness (BHR) in preschool children with asthma. Methods: One hundred nine asthmatic children age 4-6 years were enrolled. Total serum IgE levels, and specific IgE level to food and inhalant allergens were tested using Pharmacia Auto CAP system RAST(R)FEIA, methacholine bronchial challenge test (PCw=Provocative concentration at wheezing. PCsat=Provocative concentration at 5% fall of oxygen saturation) were performed in all subjects. They were divided into 3 groups according to the serum IgE level:less than 120 IU/mL (group A, n=38), 120 to 1,000 IU/mL (group B, n=45), and greater than 1,000 IU/mL (group C, n=26). The relationships with allergic sensitization and BHR were evaluatied among the 3 groups. Results: Sensitization to foods and inhalant allergens were related to a higher total serum IgE levels. However, BHR and severity of asthma were not related to higher total serum IgE levels, except in group B. Presence of atopic dermatitis, high serum eosinophil (>450/mm3), allergic sensitization to foods and inhalants were related to high serum IgE greater than 1,000 IU/mL. (odds ratio; 95% confidence interval=4.4;1.7-11.2, 3.2;1.2-9.2, 4.8;1.7-13.2, 5.5;1.2-24.9) Conclusion: Moderately elevated total serum IgE was related to allergic sensitization, severity of asthma and BHR. However highly elevated total serum IgE was related to only allergic sensitization. This may be attributed to other factors in preschool children with asthma. [Pediatr Allergy Respir Dis(Korea) 2009;19:260-270]

Anti-IgE mAb Suppresses Systemic Anaphylaxis through the Inhibitory IgG Receptor Fc ${\gamma}$ RIIb in Mice - Interaction between Anti-IgE and Fc ${\gamma}$ RIIb -

Kang, Nam-In,Jin, Zhe-Wu,Lee, Hern-Ku The Korean Association of Immunobiologists 2007 Immune Network Vol.7 No.3

Background: Anti-IgE mAb which binds circulating but not receptor-bound IgE has been shown to be effective in treatment for asthma and other allergic diseases. However, the mechanisms by which anti-IgE mAb influences the pathophysiological responses are remained to be illustrated. This study was undertaken to examine the therapeutic efficacy of non-anaphylactogenic anti-mouse IgE mAb using murine models of IgE-induced systemic fatal anaphylaxis. Methods: Active systemic anaphylaxis was induced by either penicillin V(Pen V) or OVA and passive systemic anaphylaxis was induced by either anaphylactogenic anti-mouse IgE or a mixture of anti-chicken gamma globulin (CGG) IgG1 mAb and CGG. The binding of the Fc portion of anti-IgE to CHO-stable cell line expressing mouse Fc ${\gamma}$ RIIb was examined using flow cytometry. Fc fragments of anti-IgE mAb were prepared using papain digestion. The expression of phosphatases in lungs were assessed by Western blotting and immunohistochemistry. Results: Anti-IgE mAb prevented IgE- and IgG-induced active and passive systemic fatal reactions. In both types of anaphylaxis, anti-IgE mAb suppressed antigen-specific IgE responses, but not those of IgG. Anti-IgE mAb neither prevented anaphylaxis nor suppressed the IgE response in Fc ${\gamma}$ RIIb-deficient mice. The Fc portion of anti-IgE mAb was bound to murine Fc ${\gamma}$ RIIb gene-transfected CHO cells and inhibited systemic anaphylaxis. Anti-IgE mAb blocked the anaphylaxis-induced downregulation of Fc ${\gamma}$ RIIb-associated phosphatases such as src homology 2 domain-containing inositol 5-phosphatase (SHIP) and phosphatase and tensin homologue deleted on chromosome ten (PTEN). Conclusion: Anti-IgE mAb prevented anaphylaxis by delivering nonspecific inhibitory signals through the inhibitory IgG receptor, Fc ${\gamma}$ RIIb, rather than targeting IgE.

학동전기 천식환자에서 혈청 총 IgE와 항원감작 및 기관지과민성과의 관계

전재성,강임주,윤기태 대한 소아알레르기 호흡기학회 2009 Allergy Asthma & Respiratory Disease Vol.19 No.3

Purpose : This study aimed to evaluate the relationship between the serum IgE level and allergic sensitization/bronchial hyperresponsiveness (BHR) in preschool children with asthma. Methods : One hundred nine asthmatic children age 4-6 years were enrolled. Total serum IgE levels, and specific IgE level to food and inhalant allergens were tested using Pharmacia Auto CAP system RAST®FEIA, methacholine bronchial challenge test (PCw=Provocative concentration at wheezing. PCsat=Provocative concentration at 5% fall of oxygen saturation) were performed in all subjects. They were divided into 3 groups according to the serum IgE level : less than 120 IU/mL (group A, n=38), 120 to 1,000 IU/mL (group B, n=45), and greater than 1,000 IU/mL (group C, n=26). The relationships with allergic sensitization and BHR were evaluatied among the 3 groups. Results : Sensitization to foods and inhalant allergens were related to a higher total serum IgE levels. However, BHR and severity of asthma were not related to higher total serum IgE levels, except in group B. Presence of atopic dermatitis, high serum eosinophil (>450/mm3), allergic sensitization to foods and inhalants were related to high serum IgE greater than 1,000 IU/mL. (odds ratio ; 95% confidence interval=4.4;1.7-11.2, 3.2;1.2-9.2, 4.8;1.7-13.2, 5.5;1.2-24.9) Conclusion : Moderately elevated total serum IgE was related to allergic sensitization, severity of asthma and BHR. However highly elevated total serum IgE was related to only allergic sensitization. This may be attributed to other factors in preschool children with asthma. 서 론 : 천식환자에서 IgE의 증가는 폐기능 및 기관지과민성과 관련이 있고 특히 항원 감작정도가 IgE의 증가에 상당한 영향을 미친다. 따라서 저자들은 학동전기 소아 천식환자에서 혈청 IgE의 증가와 항원감작 및 기관지과민성과의 관계를 알고자 본 연구를 실시하였다. 대 상 : 최근 3년간 대구파티마병원 소아청소년과 외래를 방문한 4-6세 사이의 천식 환자 중 알레르기 검사와 함께 메타콜린 흡입 후 흉부청진 즉, Provocative concentration at wheezing (PCw) 및 산소포화도 측정 Provocative concentration at 5% fall of oxygen saturation (PCsat)을 이용한 기관지과민성 검사가 가능했던 환아 109명을 혈청 IgE가 120 IU/mL 미만인 IgE 비증가군 (38명), 120-1,000 IU/mL인 중등도증가군과(45명), 1,000 IU/mL 이상의 고증가군 (26명)으로 분류하여 IgE와 천식병력, 항원 감작, 천식의 중증도 및 기관지과민성과의 관계를 비교하였다. 결 과 : 가족의 천식병력, 영아기의 모유수유, 집안의 애완동물, 간접흡연이 IgE의 증가와 관련이 없었으나(P>0.050, P=0.631, P=0.066, P=0.056), 아토피피부염의 동반과 함께 혈중 호산구 및 ECP의 증가는 IgE의 증가와 관련이 있었다.(P=0.003, P=0.000, P=0.011) 천식의 중증도와 함께 기관지과민성의 증가는 IgE의 증가와 관련이 없었으나, 음식항원, 흡입항원, 음식 및 흡입항원 동시 감작의 빈도는 IgE 증가시 감작 빈도가 유의하게 높았다.(P=0.000, P=0.000, P=0.000) IgE 고증가군의 위험요인으로 450/mm3 이상의 혈중 호산구, 아토피피부염의 동반, 음식항원 감작, 흡입항원 감작의 Odds ratio (95% Confidence interval)가 각각 3.2 (1.2-9.2), 4.4 (1.7-11.2), 4.8 (1.7-13.2), 5.5 (1.2-24.9)로 의미 있게 나타났다. 결 론 : 학동전기 소아천식환자에서 IgE의 중등도 증가는 항원감작과 및 기관지과민성과 상당한 관련이 있으나, 고증가군은 항원감작과 함께 다른 요인이 관여할 것으로 생각되며 향후 좀 더 많은 연구가 필요할 것으로 생각된다.

Anti-IgE mAb Suppresses Systemic Anaphylaxis through the Inhibitory IgG Receptor Fc γ RIIb in Mice

Kang, Nam-In,Jin, Zhe-Wu,Lee, Hern-Ku 대한면역학회 2007 Immune Network Vol.7 No.3

Anti-IgE mAb which binds circulating but not receptor-bound IgE has been shown to be effective in treatment for asthma and other allergic diseases. However, the mechanisms by which anti-IgE mAb influences the pathophysiological responses are remained to be illustrated. This study was undertaken to examine the therapeutic efficacy of non-anaphylactogenic anti-mouse IgE mAb using murine models of IgE-induced systemic fatal anaphylaxis. Methods: Active systemic anaphylaxis was induced by either penicillin V(Pen V) or OVA and passive systemic anaphylaxis was induced by either anaphylactogenic anti-mouse IgE or a mixture of anti-chicken gamma globulin (CGG) IgG1 mAb and CGG. The binding of the Fc portion of anti-IgE to CHO-stable cell line expressing mouse Fc γ RIIb was examined using flow cytometry. Fc fragments of anti-IgE mAb were prepared using papain digestion. The expression of phosphatases in lungs were assessed by Western blotting and immunohistochemistry. Results: Anti-IgE mAb prevented IgE- and IgG-induced active and passive systemic fatal reactions. In both types of anaphylaxis, anti-IgE mAb suppressed antigen-specific IgE responses, but not those of IgG. Anti-IgE mAb neither prevented anaphylaxis nor suppressed the IgE response in Fc γ RIIb-deficient mice. The Fc portion of anti-IgE mAb was bound to murine Fc γ RIIb gene-transfected CHO cells and inhibited systemic anaphylaxis. Anti-IgE mAb blocked the anaphylaxis-induced downregulation of Fc γ RIIb-associated phosphatases such as src homology 2 domain-containing inositol 5-phosphatase (SHIP) and phosphatase and tensin homologue deleted on chromosome ten (PTEN). Conclusion: Anti-IgE mAb prevented anaphylaxis by delivering nonspecific inhibitory signals through the inhibitory IgG receptor, Fc γ RIIb, rather than targeting IgE.

Induction of Rice Allergen-Specific IgE Synthesis by KU812 Cells

Sun-Yup Shim(심선엽),Yoshinori Katakura(요시노리 카타쿠라),Sanetaka Shirahata(시라하타 사네타카) 한국생명과학회 2007 생명과학회지 Vol.17 No.11

CD40L를 발현하는 KU812세포와 CD40를 발현하는 항원 특이적 B 세포의 배양을 통해 IgE 클라스 스위치가 유도된다. 본 연구자는 체외면역법에 의해 건강인의 말초혈액을 이용하여 쌀 알레르겐 특이적 IgM 항체를 생성하는 B 세포주를 수립하였다. 본 연구에서는 KU812세포에 의한 쌀 알레르겐 특이적 IgE 항체의 유도를 시도하였다. 배양 전, 쌀 알레르겐 특이적 B 세포주, RA9G11과 PMA와 ionomycin을 6시간 처리하여 활성화된 KU812세포에서 CD40와 CD40L 발현량을 flow cytomerty를 통화여 각각 확인하였다. RA9G11세포와 활성화된 KU812세포는 높은 수준의 CD40와 CD40L를 각각 발현하였다. 쌀 알레르겐 특이적 IgE항체 합성 유도를 위해, 여러 가지 농도의 IL-4 존재하에, RA9G11세포와 활성화된 KU812세포를 12일 동안 배양하였다. IgE 정상영역의 mRNA 발현량과, 쌀 알레르겐 특이적 IgE 항체 생성 세포가 모든 조건에서 확인되었으며, 특히 50U의 L-4 농도 하에서 같은 비율의 RA9G11과 활성화된 KU812세포를 배양했을 때, IgE 합성이 가장 높았다. 따라서 활성화된 KU812세포에 의한 쌀 알레르겐 특이적 IgE 합성은 알레르기 질환의 치료 및 예방에 관한 연구에 기여할 것으로 사료된다. In vitro IgE class switching could be induced through co-culture of CD40L-expressing KU812 cells and CD40-expressing B cells in the presence of IL-4 or IL-13. It has been generated several B cell lines, which produce rice allergen (RA)-specific IgM antibody by in vitro immunization (IVI) using peripheral blood lymphocyte (PBL). In this study, induction of RA-specific IgE antibody by KU812 cells was attempted. Before co-culture, we determined the CD40 expression in RA-specific B cell lines, RA9G11 and the CD40 ligand (CD40L) expression in activated KU812 cells by treatments with phorbol myristate acetate (PMA) and ionomycin for 6 hrs. Flow cytometric analysis shown that RA9G11 and activated KU812 cells expressed high level of CD40 and CD40L, respectively. RA9G11 cells were cultured with activated KU812 cells for 12 days in the presence of IL-4 for IgE class switching. Mature Cε mRNA level and RA-specific IgE spot forming cells (SFC) were observed in all culture condition, and especially, high level of RA-specific IgE synthesis was determined the same ratio of RA9G11 and activated KU812 cells in the presence of 50U IL-4. Therefore, induction of RA-specific IgE synthesis by activated KU812 cells can be contributed in the application for allergic therapy and prevention.

총 IgE의 신속한 정량 측정을 위한 ImmuneCheck IgE의 임상적 유용성

이신행 ( Shinhaeng Lee ),최진영 ( Jinyoung Choi ),최은주 ( Eunju Choe ),이상철 ( Sang Chul Lee ),박경희 ( Kyung Hee Park ),이재현 ( Jae-hyun Lee ),박중원 ( Jung-won Park ) 대한천식알레르기학회 2018 Allergy Asthma & Respiratory Disease Vol.6 No.6

Purpose: Conventional serum IgE assay was costly, required the skills of expert, and relied heavily on expensive equipment. Quantitative measurement of total IgE using Point of Care Test (POCT) device can be the solution for these limitations. This study evaluated and validated the reproducibility of ImmuneCheck IgE. Methods: This study included 120 patients of allergic diseases such as allergic rhinitis, asthma, drug allergy, food allergy, atopic dermatitis, or anaphylaxis . The reliability of POCT ImmuneCheck IgE was evaluated by comparing results from the naked eye and from the Q-Reader. Intratest reproducibility and intertest correlation were analyzed using intraclass correlation coefficient (ICC). Results: Of the 120 enrolled patients, 51 were males and 69 were females. The ages ranged from 19 to 84 years, with an average age of 51.5 years. The concentration of serum total IgE measured by Phadia ImmunoCAP IgE ranged from 5.95 to 5,000 IU/mL. ICC for Intratest reproducibility of ImmuneCheck IgE by naked eye and by Q-Reader were 0.991 (P<0.001) and 0.989 (P<0.001), respectively. In addition, intertest correlation between ImmuneCheck IgE and Phadia ImmunoCAP IgE results of naked eye and Q-Reader were 0.968 (P<0.001) and 0.948 (P<0.001), respectively. Conclusion: The ImmuneCheck IgE was reproducible and highly correlated with conventional Phadia ImmunoCAP IgE assay. This result suggests that ImmuneCheck IgE can be a useful tool for rapid and precise detection of total IgE. (Allergy Asthma Respir Dis 2018;6:310-314)

Usefulness of Total IgE in Predicting Positive Allergen Specific IgE Tests in Korean Subjects

정승원,오은지,이제훈,김용구,김수영,김영식,박용진 대한진단검사의학회 2010 Annals of Laboratory Medicine Vol.30 No.6

Background : Total IgE levels in allergic patients tend to be higher than those in healthy individuals. We evaluated the usefulness of total IgE levels in predicting positive results of allergen specific IgEs in multiple allergen simultaneous tests. Methods : A total of 133 patients with allergic symptoms were evaluated. Allergen specific IgEs were detected using 3 different kits: Allergy screen (R-biopharm, Germany), AdvanSure Allergy Screen (LG Life Science, Korea) and Polycheck allergy (Biocheck Co., Germany). Total IgE was measured by turbidoimmunometric assay (LX-2200, Eiken Chemical Co., Japan). The patients were divided into high (≥170 IU/mL) and low (<170 IU/mL) groups of total IgE level, and the positive rates and number of positive allergen specific IgEs were evaluated in each group. Positive concordance rates among different kits were also evaluated. Results : High total IgE group showed significantly higher positive rates and number of positive allergen specific IgEs in all of the 3 test kits used compared to low total IgE group. Only two of the allergens, Dermatophagoides farinae and Dermatophagoides pteronyssinus had positive concordance rates of ≥50%. Allergen specific IgEs to these two allergens showed good correlation with total IgE (correlation coefficients >0.5). Conclusions : Total IgE appears to be useful in predicting positive results in allergen specific IgE tests to common allergens. The specific IgEs to D. farinae and D. pteronyssinus showed good correlation with total IgE. However, for other allergens, significant differences were observed among different test kits, and the standardization of allergens in multiple allergen simultaneous tests is needed. (Korean J Lab Med 2010;30:660-7)

알레르기 환자에서 혈청 IgE와 특이항원 양성율의 일치도

남해선,권준택,박준수 순천향의학연구소 2000 Journal of Soonchunhyang Medical Science Vol.6 No.2

To evaluate usefulness of serum IgE to determine specific allergens, authors conducted priest IgE and MAST-CLA allergen-specific IgE assays in 78 allergic patients diagnosed at Soonchunhyang University Chunan Hospital during October 1998 through July 2000. During the study period, inhalent and food Korean panels were applied in 57 (73.1%) and 21 outpatients (26.9%), respectively. Kappa index was calculated to evaluate the agreement of priest IgE with Total IgE and allergen-specific IgE by MAST-CLA. 1. The men (±SD) age was 13.2 (±14.1) year-old and male accounted for 62.8%. 2. The overall positive rate of priest IgE was 66.7% and mean (±SD) level of priest IgE was 271.2 (±265.6) IU/ml 3. Patients with more than one specific allergen and with elevated total IgE by MAST-CLA were 25 (32.1%) and 33 (42.3%), respectively. 4. Significant agreement between total IgE and allergen-specific IgE was shown, but strength of agreement was slight (Kappa = 0.186, P = 0.046), 5. While no significant agreement between priest IgE and total IgE was observer, the priest IgE agreed significantly with allergen-specific IgE (Kappa = 0.153, P=0.043) In conclusion, our data suggested that serum priest IgE is more likely associated with allergen-specific IgE than total IgE in MAST-CLA assay. Furthermore, it is recommended that Korean panel of MAST-CLA should contain more specific allergens.

태아 및 산모 혈청 IgE수치 측정 방법평가

박천욱(Chun Wook Park),이종육(Jong Yuk Yi),김형옥(Hyung Ok Kim),김정원(Chung Won Kim) 대한피부과학회 1986 大韓皮膚科學會誌 Vol.24 No.2

The aim of the present work is to evaluate the most accurate technique for analysirig low levels of serum IgE. Following results are obtained from experiments by PRIST, Overnight PRIST, PRIST using RAST anti-IgE tracer and Overnight PRIST using RAST anti-IgE tracer methods with cord serum and maternal serum of 21 individuals respectively. 1) There was no statistical significance in maternal serum IgE titer using above 4 methods. However, the higher level of IgE titer was found in PRIST method when IgE was over 190 IU/ml(5 cases) estimated by PRIST method and in Overnight PRIST using RAST anti-IgE tracer method when Ig.E was below lgp IU/ml (16 cases) (p40.05). 2) In cord serum IgE titer, only Overnight PRIST using RAST anti-IgE tracer method showed statistical significance. 3) The most desirable correlation coefficient between maternal serum and cord serum IgE titer was estimated by Overnight PRIST using RAST anti-IgE tracer method than any other rnethods.

RIST 法을 利用한 血淸 IgE 測定法에 關한 檢討

張喆守 ; 閔在基 김천대학교 1986 김천대학교 논문집 Vol.7 No.-

This study was performed to determination methods in serum IgE with RIST. In this work, measure of phadebas IgE test kit(Pharmacia, Sweden) with redioimmunoassay. The following results were obtained. ①Reproducibility of each standard solution in this phadebas IgE test kit interassay were 4.4~14.9%, but intraassay were 4.8~13.8%. Shortening within 20~35 hours of incubation time in IgE levels determina-tion ②There was 70 significent different between serum IgE levels and measured serum IgE levels in dilutied(X10) serum. ③In recovery test was satisfactory within 95~105% up to added 5U/m IgE levels. ④The comparison of regression equation and correlation coefficient between stock frojen for a week serum IgE levels and premeasured serum IgE levels show Y=1.6+42.7 r=0.985 ⑤Mean serum IgE Value of 69. healthy Koreans was 287 162U/m. The difference of the mean serum IgE levels among each age grops was not statistical significant. There was also no significant difference between male and female.