Oral desensitization therapy for peanut allergy induces dynamic changes in peanut-specific immune responses.
Oral desensitization therapy for peanut allergy induces dynamic changes in peanut-specific immune responses.
复制标题
DOI：
10.1111/all.15276
复制
发表时间：
2022-08
期刊：
影响因子：
12.4
通讯作者：
Wambre, Erik
中科院分区：
文献类型：
--
作者：
Bajzik, Veronique;DeBerg, Hannah A.;Garabatos, Nahir;Rust, Blake J.;Obrien, Kimberly K.;Nguyen, Quynh-Anh;O'Rourke, Colin;Smith, Alex;Walker, Alex H.;Quinn, Charlie;Gersuk, Vivian H.;Farrington, Mary;Jeong, David;Vickery, Brian P.;Adelman, Daniel C.;Wambre, Erik
栅栏研究是一项关于AR 101的花生口服免疫疗法（POIT）的国际III期试验，导致对花生高度过敏的儿童和青少年脱敏。对食物过敏原免疫疗法诱导的免疫机制的更好理解将使更明智和有效的治疗策略成为可能。我们的主要目的是检查血液样本中的免疫学变化，这些样本来自接受AR 101口服脱敏免疫治疗的花生过敏个体的子集。作为入组筛选的一部分和在栅栏研究期间的多个时间点获得的血液样品用于评估嗜碱性粒细胞和CD 4 + T细胞对花生的反应性。与DBPCFC反应者相比，对进入双盲安慰剂对照花生激发（DBPCFC）的临床反应性的缺乏伴随着对花生的嗜碱性粒细胞敏感性和T细胞反应性的显著降低。在基线时，在许多但不是所有的花生过敏患者中观察到花生反应性TH 2A细胞，其在外周血中的水平与T细胞对花生的反应性以及血清花生特异性IgE和IgG 4水平相关。POIT以亚群依赖性方式重塑循环花生反应性T细胞应答。嗜碱性粒细胞和T细胞对花生反应的变化与AR 101治疗的临床益处密切相关，并且与对花生临床敏感性较低的患者的反应相似。然而，未观察到组间花生反应性Treg细胞频率的差异。AR 101的口服脱敏疗法导致嗜碱性粒细胞对花生的敏感性降低，并重塑花生反应性T效应细胞应答，支持其作为免疫调节疗法的潜力。CRTH 2 + pTeff细胞和CCR 6 + pTeff细胞代表两种相互排斥的、不重叠的涉及食物过敏性疾病的细胞和分子实体。循环中的CRTH 2 + pTeff细胞主要局限于对100 mg DBPCFC有反应的花生过敏个体，而对花生的临床敏感性较低。嗜碱性粒细胞和T细胞对花生的反应变化与POIT的临床获益密切相关，与对基线100 mg DBPCFC无反应的患者的反应相似。缩略语：BAT-EC 50，嗜碱性粒细胞活化试验中对应于嗜碱性粒细胞50%最大活化的变应原浓度; CCR 6，C-C基序趋化因子受体6; CRTH 2，Th 2细胞上表达的化学引诱物受体同源分子; DBPCFC，双盲安慰剂对照花生激发; FOXP 3，叉头盒P3; freq，频率; GATA 3，加塔结合蛋白3; HPGDS，造血前列腺素D合酶; IFNG，干扰素γ; IL，白细胞介素;栅栏，AR 101用于儿童和成人脱敏的花生过敏口服免疫疗法研究; POIT，花生口服免疫疗法; PPARG，过氧化物酶体增殖物激活受体α; pTeff，花生反应性T细胞; RORC，RAR相关孤儿受体C; ST 2，致瘤性抑制2
The PALISADE study, an international, phase 3 trial of peanut oral immunotherapy (POIT) with AR101, resulted in desensitization in children and adolescents who were highly allergic to peanut. An improved understanding of the immune mechanism induced in response to food allergen immunotherapy would enable more informed and effective therapeutic strategies. Our main purpose was to examine the immunologic changes in blood samples from a subset of peanut-allergic individuals undergoing oral desensitization immunotherapy with AR101. Blood samples obtained as part of enrollment screening and at multiple time-points during PALISADE study were used to assess basophil and CD4+ T cell reactivity to peanut. Absence of clinical reactivity to the entry double-blinded placebo-controlled peanut challenge (DBPCFC) was accompanied by a significantly lower basophil sensitivity and T cell reactivity to peanut compared to DBPCFC reactors. At baseline, peanut-reactive TH2A cells were observed in many but not all peanut allergic patients and their level in peripheral blood correlate with T cell reactivity to peanut and with serum peanut-specific IgE and IgG4 level. POIT reshaped circulating peanut-reactive T cell responses in a subset dependent manner. Changes in basophil and T cell responses to peanut closely paralleled clinical benefits to AR101 therapy and resemble responses in those with lower clinical sensitivity to peanut. However, no difference in peanut reactive Treg cell frequency was observed between groups. Oral desensitization therapy with AR101 leads to decreased basophil sensitivity to peanut and reshapes peanut-reactive T effector cell responses supporting its potential as an immunomodulatory therapy. CRTH2+ pTeff cells and CCR6+ pTeff cells represent two mutually exclusive, non-overlapping cellular and molecular entities involved in food allergic diseases. Circulating CRTH2+ pTeff cells are mostly restricted to peanut allergic individualswho react to the 100 mg DBPCFC compared to those with lower clinical sensitivityto peanut. Changes in basophil and T cell responses to peanut closely parallel clinical benefitsto POIT and resemble responses in those that did not react to the baseline 100 mg DBPCFC. Abbreviations: BAT-EC50, concentration of allergen corresponding to 50% of maximal activation of basophils in basophil activation test; CCR6, C-C motif chemokine receptor 6; CRTH2, chemoattractant receptor-homologous molecule expressed on Th2 cells; DBPCFC, double-blinded placebo-controlled peanut challenge; FOXP3, forkhead box P3; freq, frequency; GATA3, GATA binding protein 3; HPGDS, hematopoietic prostaglandin D synthase; IFNG, interferon gamma; IL, interleukin; PALISADE, Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults; POIT, peanut oral immunotherapy; PPARG, peroxisome proliferator activated receptor alpha; pTeff, peanut-reactive T cell; RORC, RAR related orphan receptor C; ST2, suppression of tumorigenicity 2
登录
查看更多内容
DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
14.2
作者：
Chiang, David;Chen, Xintong;Berin, M. Cecilia
通讯作者：
Berin, M. Cecilia
影响因子：
14.2
作者：
Ford, Lara S.;Bloom, Katherine A.;Nowak-Wegrzyn, Anna H.;Shreffler, Wayne G.;Masilamani, Madhan;Sampson, Hugh A.
通讯作者：
Sampson, Hugh A.
影响因子：
2.6
作者：
Dunlop, Joan H.;Keet, Corinne A.
通讯作者：
Keet, Corinne A.
影响因子：
6.1
作者：
Archila, L. D.;DeLong, J. H.;Kwok, W. W.
通讯作者：
Kwok, W. W.