白细胞介素10受体1在食物过敏儿童外周血T淋巴细胞中的表达
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摘要
目的研究白细胞介素10受体1(IL-10R1)在食物过敏儿童外周血T淋巴细胞的表达及其临床意义。方法选择2017-07-01至2017-12-31在北京大学第三医院儿科食物过敏门诊诊断为食物过敏的50例患儿作为食物过敏组,选择同期在北京大学第三医院儿童健康发展中心行健康体检的25名儿童作为对照组。采用流式细胞技术检测IL-10R1在两组儿童外周血CD4~+T及CD8~+T淋巴细胞表达阳性率及平均荧光强度值(MFI)。同时比较IL-10R1在过敏原特异性IgE阳性与阴性食物过敏患儿外周血CD4~+T及CD8~+T淋巴细胞表达阳性率及MFI。根据食物过敏患儿症状、体征严重程度进行赋值评分,分析食物过敏患儿IL-10R1在外周血CD4~+T及CD8~+T淋巴细胞表达阳性率与食物过敏症状、体征评分有无相关性。结果 IL-10R1在食物过敏组患儿外周血CD4~+T及CD8~+T淋巴细胞表达阳性率和MFI均低于对照组,IL-10R1在食物过敏组CD4~+T淋巴细胞表达阳性率和MFI中位数分别为40.23、12.18;在对照组CD4~+T2.506、-5.457;P值分别为0.012、0.000)。IL-10R1在食物过敏组CD8~+T淋巴细胞表达阳性率和MFI中位数分别中位数分别为39.46、17.28(Z值分别为-4.035、-5.226;P值分别为0.000、0.000)。IL-10R1在过敏原特异性IgE阳性与阴性患儿外周血CD4~+T及CD8~+T淋巴细胞表达阳性率及MFI没有差异。食物过敏患儿IL-10R1在外周血CD4~+T及CD8~+T淋巴细胞表达阳性率与食物过敏症状、体征评分无相关性。结论 IL-10R1在外周血CD4~+T淋巴细胞和CD8~+T淋巴细胞表面表达减少可能与食物过敏发病有关;IL-10R1在外周血CD4~+T淋巴细胞和CD8~+T淋巴细胞表面表达在IgE和非IgE介导的食物过敏发病过程中均起作用;IL-10R1在外周血CD4~+T淋巴细胞和CD8~+T淋巴细胞表面表达可能与食物过敏发病严重程度无关。
Objective To study on the expression and clinical significance of interleukin 10 receptor 1(IL-10R1)in T lymphocytes in peripheral blood of children with food allergy. Methods The food allergy group included 50 cases of children admitted in Department of Pediatrics of Peking University Third Hospital from July 1,2017 to December 31,2017 and were diagnosed with food allergy. A total of 25 cases of healthy children who visited Child Health and Development Center of Peking University Third Hospital in the same period with no food allergy manifestation were selected as a healthy control group. The clinical manifestations of food allergy in different age groups were compared.Flow cytometry was used to examine the expression of IL-10R1 in CD4~+T cells and CD8~+T cells in peripheral blood and the MFI. According to the results of allergen specific Ig E test,the food allergy children were classified as allergen specific Ig E positive group and negative group. The expression of l L-10R1 in the CD4~+T lymphocytes and CD8~+T lymphocytes in peripheral blood and the MFI of the two groups were compared. A severity index of clinical symptoms and signs of food allergy was used to grade illness severity of food allergy children. Then it analyzed the correlation between the expression rates of IL-10R1 in CD4~+T cells and CD8~+T cells in peripheral blood and the scores. Results The expression rates and MFI of IL-10R1 in CD4~+T cells in peripheral blood of food allergy group were lower compared to the control group. The median expression rates and MFI were 40.23 versus 45.32,12.18 versus 17.69(Z=-2.506,-5.547,P=0.012,0.000,respectively). The expression rates and MFI of IL-10R1 in CD8~+T cells in the peripheral blood of food allergy group were also lower than the control group. The median expression rates and MFI were 34.50 versus 39.46,12.47 versus 17.28(Z=-4.035,-5.226,P=0.000,0.000,respectively). IL-10R1 expression rates and MFI on CD4~+T cells and CD8~+T cells in peripheral blood of allergen specific Ig E positive group were similar to those of the negative group. The expression rates of IL-10R1 on CD4~+T cells and CD8~+T cells in peripheral blood of children with food allergy had no correlation with the symptom and sign scores of food allergy. Conclusion The decrease of the expression of IL-10R1 in CD4~+T cells and CD8~+T cells in peripheral blood may be associated with food allergy of children;the expression of IL-10R1 may be involved in the pathogenesis of food allergy mediated by Ig E and non-Ig E,but it was not associated with the severity of food allergy.
Objective To study on the expression and clinical significance of interleukin 10 receptor 1(IL-10R1)in T lymphocytes in peripheral blood of children with food allergy. Methods The food allergy group included 50 cases of children admitted in Department of Pediatrics of Peking University Third Hospital from July 1,2017 to December 31,2017 and were diagnosed with food allergy. A total of 25 cases of healthy children who visited Child Health and Development Center of Peking University Third Hospital in the same period with no food allergy manifestation were selected as a healthy control group. The clinical manifestations of food allergy in different age groups were compared.Flow cytometry was used to examine the expression of IL-10R1 in CD4~+T cells and CD8~+T cells in peripheral blood and the MFI. According to the results of allergen specific Ig E test,the food allergy children were classified as allergen specific Ig E positive group and negative group. The expression of l L-10R1 in the CD4~+T lymphocytes and CD8~+T lymphocytes in peripheral blood and the MFI of the two groups were compared. A severity index of clinical symptoms and signs of food allergy was used to grade illness severity of food allergy children. Then it analyzed the correlation between the expression rates of IL-10R1 in CD4~+T cells and CD8~+T cells in peripheral blood and the scores. Results The expression rates and MFI of IL-10R1 in CD4~+T cells in peripheral blood of food allergy group were lower compared to the control group. The median expression rates and MFI were 40.23 versus 45.32,12.18 versus 17.69(Z=-2.506,-5.547,P=0.012,0.000,respectively). The expression rates and MFI of IL-10R1 in CD8~+T cells in the peripheral blood of food allergy group were also lower than the control group. The median expression rates and MFI were 34.50 versus 39.46,12.47 versus 17.28(Z=-4.035,-5.226,P=0.000,0.000,respectively). IL-10R1 expression rates and MFI on CD4~+T cells and CD8~+T cells in peripheral blood of allergen specific Ig E positive group were similar to those of the negative group. The expression rates of IL-10R1 on CD4~+T cells and CD8~+T cells in peripheral blood of children with food allergy had no correlation with the symptom and sign scores of food allergy. Conclusion The decrease of the expression of IL-10R1 in CD4~+T cells and CD8~+T cells in peripheral blood may be associated with food allergy of children;the expression of IL-10R1 may be involved in the pathogenesis of food allergy mediated by Ig E and non-Ig E,but it was not associated with the severity of food allergy.
引文
[1]Kleine-Tebbe J,Wa?mann-Otto A,M?nnikes H.Food allergy and intolerance:Distinction,definitions and delimitation[J].Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz,2016,59(6):705-722.
[2]Wang X,Sherman A,Liao G,et al.Mechanism of oral tolerance induction to therapeutic proteins[J].Adv Drug Deliv Rev,2013,65(6):759-773.
[3]Michaud B,Aroulandom J,Baiz N,et al.Casein-specific IL-4-and IL-13-secreting T cells:a tool to implement diagnosis of cow's milk allergy[J].Allergy,2014,69(11):1473-1480.
[4]De Long JH,Simpson KH,Wambre E,et al.Ara h 1-reactive Tcells in individuals with peanut allergy[J].J Allergy Clin Immu?nol,2011,127(5):1211-1218.
[5]Shen Y,Hu GH,Kang HY,et al.Allergen induced Treg re?sponse in the peripheral blood mononuclear cells(PBMCs)of patients with nasal polyposis[J].Asian Pac J Allergy Immunol,2014,32(4):300-307.
[6]Krogulska A,Borowiec M,Polakowska E,et al.FOXP3,IL-10,and TGF-βgenes expression in children with Ig E-dependent food allergy[J].J Clin Immunol,2011,31(2):205-215.
[7]Sabat R,Grütz G,Warszawska K,et al.Biology of interleukin-10[J].Cytokine Growth Factor Rev,2010,21(5):331-344.
[8]Muraro A,Werfel T,Hoffmann-Sommergruber K,et al.EAACIfood allergy and anaphylaxis guidelines:diagnosis and manage?ment of food allergy[J].Allergy,2014,69(8):1008-1025.
[9]Ebisawa M,Ito K,Fujisawa T.Japanese guidelines for food aller?gy 2017[J].Allergol Int,2017,66(2):248-264.
[10]中华医学会儿科学分会儿童保健学组.婴幼儿食物过敏诊治建议专家共识[J].中华儿科杂志,2011,49(5):344-348.
[11]中华医学会儿科学分会消化学组.食物过敏相关消化道疾病诊断与管理专家共识[J].中华儿科杂志,2017,55(7):487-492.
[12]Koletzko S,Niggemann B,Arato A,et al.Diagnostic approach and management of cow’s-milk protein allergy in infants and children:ESPGHAN GI Committee practical guidelines[J].JPediatr Gastroenterol Nutr,2012,55(2):221-229.
[13]Ballmer-Weber BK.Food allergy in adolescence and adult?hood[J].Chem Immunol Allergy,2015,101:51-58.
[14]Fiocchi A,Pecora V,Petersson CJ,et al.Sensitization pattern to inhalant and food allergens in symptomatic children at first evaluation[J].Ital J Pediatr,2015,41:96.
[15]Archila LD,Jeong D,Pascal M,et al.Jug r 2-reactive CD4+Tcells have a dominant immune role in walnut allergy[J].J Al?lergy Clin Immunol,2015,136(4):983-992.
[16]Brooks DG,Walsh KB,Elsaesser H,et al.IL-10 directly sup?presses CD4 but not CD8 T cell effector and memory responses following acute viral infection[J].Proc Natl Acad Sci U S A,2010,107(7):3018-3023.
[17]Swamy M,Abeler-D?rner L,Chettle J,et al.Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance[J].Nat Commun,2015,6:7090.
[18]Yamada A,Ohshima Y,Yasutomi M,et al.Antigen-primed splenic CD8+T cells impede the development of oral antigeninduced allergic diarrhea[J].J Allergy Clin Immunol,2009,123(4):889-894.
[19]Emmerich J,Mumm JB,Chan IH,et al.IL-10 directly acti?vates and expands tumor-resident CD8+T cells without de novo infiltration from secondary lymphoid organs[J].Cancer Res,2012,72(14):3570-3581.
[20]Renz H,Allen KJ,Sicherer SH,et al.Food allergy[J].Nat Rev Dis Primers,2018,4:17098
[21]Wang T,Li Z,Li X,et al.Expression of CD19+CD24highCD38high B cells,IL-10 and IL-10R in peripheral blood from patients with systemic lupus erythematosus[J].Mol Med Rep,2017,16(5):6326-6333.
[2]Wang X,Sherman A,Liao G,et al.Mechanism of oral tolerance induction to therapeutic proteins[J].Adv Drug Deliv Rev,2013,65(6):759-773.
[3]Michaud B,Aroulandom J,Baiz N,et al.Casein-specific IL-4-and IL-13-secreting T cells:a tool to implement diagnosis of cow's milk allergy[J].Allergy,2014,69(11):1473-1480.
[4]De Long JH,Simpson KH,Wambre E,et al.Ara h 1-reactive Tcells in individuals with peanut allergy[J].J Allergy Clin Immu?nol,2011,127(5):1211-1218.
[5]Shen Y,Hu GH,Kang HY,et al.Allergen induced Treg re?sponse in the peripheral blood mononuclear cells(PBMCs)of patients with nasal polyposis[J].Asian Pac J Allergy Immunol,2014,32(4):300-307.
[6]Krogulska A,Borowiec M,Polakowska E,et al.FOXP3,IL-10,and TGF-βgenes expression in children with Ig E-dependent food allergy[J].J Clin Immunol,2011,31(2):205-215.
[7]Sabat R,Grütz G,Warszawska K,et al.Biology of interleukin-10[J].Cytokine Growth Factor Rev,2010,21(5):331-344.
[8]Muraro A,Werfel T,Hoffmann-Sommergruber K,et al.EAACIfood allergy and anaphylaxis guidelines:diagnosis and manage?ment of food allergy[J].Allergy,2014,69(8):1008-1025.
[9]Ebisawa M,Ito K,Fujisawa T.Japanese guidelines for food aller?gy 2017[J].Allergol Int,2017,66(2):248-264.
[10]中华医学会儿科学分会儿童保健学组.婴幼儿食物过敏诊治建议专家共识[J].中华儿科杂志,2011,49(5):344-348.
[11]中华医学会儿科学分会消化学组.食物过敏相关消化道疾病诊断与管理专家共识[J].中华儿科杂志,2017,55(7):487-492.
[12]Koletzko S,Niggemann B,Arato A,et al.Diagnostic approach and management of cow’s-milk protein allergy in infants and children:ESPGHAN GI Committee practical guidelines[J].JPediatr Gastroenterol Nutr,2012,55(2):221-229.
[13]Ballmer-Weber BK.Food allergy in adolescence and adult?hood[J].Chem Immunol Allergy,2015,101:51-58.
[14]Fiocchi A,Pecora V,Petersson CJ,et al.Sensitization pattern to inhalant and food allergens in symptomatic children at first evaluation[J].Ital J Pediatr,2015,41:96.
[15]Archila LD,Jeong D,Pascal M,et al.Jug r 2-reactive CD4+Tcells have a dominant immune role in walnut allergy[J].J Al?lergy Clin Immunol,2015,136(4):983-992.
[16]Brooks DG,Walsh KB,Elsaesser H,et al.IL-10 directly sup?presses CD4 but not CD8 T cell effector and memory responses following acute viral infection[J].Proc Natl Acad Sci U S A,2010,107(7):3018-3023.
[17]Swamy M,Abeler-D?rner L,Chettle J,et al.Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance[J].Nat Commun,2015,6:7090.
[18]Yamada A,Ohshima Y,Yasutomi M,et al.Antigen-primed splenic CD8+T cells impede the development of oral antigeninduced allergic diarrhea[J].J Allergy Clin Immunol,2009,123(4):889-894.
[19]Emmerich J,Mumm JB,Chan IH,et al.IL-10 directly acti?vates and expands tumor-resident CD8+T cells without de novo infiltration from secondary lymphoid organs[J].Cancer Res,2012,72(14):3570-3581.
[20]Renz H,Allen KJ,Sicherer SH,et al.Food allergy[J].Nat Rev Dis Primers,2018,4:17098
[21]Wang T,Li Z,Li X,et al.Expression of CD19+CD24highCD38high B cells,IL-10 and IL-10R in peripheral blood from patients with systemic lupus erythematosus[J].Mol Med Rep,2017,16(5):6326-6333.