{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:58:42Z","timestamp":1790863122182,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023447","name":"CHU Sainte-Justine Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>While oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE\/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1198173","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T08:31:33Z","timestamp":1687941093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial"],"prefix":"10.3389","volume":"10","author":[{"given":"Camille","family":"Braun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Azzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Gingras-Lessard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9milie","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Samaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Paradis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Des Roches","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"B\u00e9gin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"974250","DOI":"10.3389\/falgy.2022.974250","article-title":"Transitioning peanut oral immunotherapy to clinical practice","volume":"3","author":"Lazizi","year":"2022","journal-title":"Front Allergy."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1016\/S0140-6736(13)62301-6","article-title":"Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial","volume":"383","author":"Anagnostou","year":"2014","journal-title":"Lancet Lond Engl."},{"key":"B3","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.jaip.2018.10.048","article-title":"Efficacy, safety, and quality of life in a multicenter, randomized, placebo-controlled trial of low-dose peanut oral immunotherapy in children with peanut allergy","volume":"7","author":"Blumchen","year":"2019","journal-title":"J Allergy Clin Immunol Pract."},{"key":"B4","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.jaci.2010.12.1111","article-title":"A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response","volume":"127","author":"Varshney","year":"2011","journal-title":"J Allergy Clin Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/S0140-6736(21)02390-4","article-title":"Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study","volume":"399","author":"Jones","year":"2022","journal-title":"Lancet Lond Engl."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1056\/NEJMoa1812856","article-title":"AR101 oral immunotherapy for peanut allergy","volume":"379","year":"2018","journal-title":"N Engl J Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaci.2017.11.004","article-title":"Treatment for food allergy","volume":"141","author":"Burks","year":"2018","journal-title":"J Allergy Clin Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1111\/all.13124","article-title":"Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis","volume":"72","author":"Nurmatov","year":"2017","journal-title":"Allergy."},{"key":"B9","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.jaci.2013.11.007","article-title":"Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy","volume":"133","author":"Vickery","year":"2014","journal-title":"J Allergy Clin Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S2352-4642(17)30041-X","article-title":"Long-term clinical and immunological effects of probiotic and peanut oral immunotherapy after treatment cessation: 4-year follow-up of a randomised, double-blind, placebo-controlled trial","volume":"1","author":"Hsiao","year":"2017","journal-title":"Lancet Child Adolesc Health."},{"key":"B11","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/ni.2256","article-title":"IgE+ memory B cells and plasma cells generated through a germinal-center pathway","volume":"13","author":"Talay","year":"2012","journal-title":"Nat Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.immuni.2012.02.009","article-title":"Fluorescent in vivo detection reveals that IgE+ B cells are restrained by an intrinsic cell fate predisposition","volume":"36","author":"Yang","year":"2012","journal-title":"Immunity."},{"key":"B13","doi-asserted-by":"publisher","first-page":"715","DOI":"10.3389\/fimmu.2019.00715","article-title":"Non-classical B cell memory of allergic IgE responses","volume":"10","author":"Saunders","year":"2019","journal-title":"Front Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1016\/j.jaci.2017.01.018","article-title":"Lifelong memory responses perpetuate humoral TH2 immunity and anaphylaxis in food allergy","volume":"140","author":"Jim\u00e9nez-Saiz","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jaci.2015.03.026","article-title":"Peanut oral immunotherapy transiently expands circulating Ara h 2\u2013specific B cells with a homologous repertoire in unrelated subjects","volume":"136","author":"Patil","year":"2015","journal-title":"J Allergy Clin Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s11882-019-0894-y","article-title":"Biomarkers in food allergy immunotherapy","volume":"19","author":"Hardy","year":"2019","journal-title":"Curr Allergy Asthma Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"AB194","DOI":"10.1016\/j.jaci.2015.12.765","article-title":"Peanut and Arah2 specific immunoglobulin E is predictive of sustained unresponsiveness following peanut oral immunotherapy","volume":"137","author":"Hickey","year":"2016","journal-title":"J Allergy Clin Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.jaci.2013.12.1037","article-title":"Peanut oral immunotherapy results in increased antigen-induced Treg function and hypomethylation of FOXP3","volume":"133","author":"Syed","year":"2014","journal-title":"J Allergy Clin Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"107612","DOI":"10.1016\/j.intimp.2021.107612","article-title":"A review on applications of abatacept in systemic rheumatic diseases","volume":"96","author":"Liu","year":"2021","journal-title":"Int Immunopharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/S0196-9781(03)00083-4","article-title":"Targeting ICAM-1\/LFA-1 interaction for controlling autoimmune diseases: designing peptide and small molecule inhibitors","volume":"24","author":"Anderson","year":"2003","journal-title":"Peptides."},{"key":"B21","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/s12276-020-0435-8","article-title":"Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development","volume":"52","author":"Hwang","year":"2020","journal-title":"Exp Mol Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1146\/annurev.immunol.21.120601.141110","article-title":"T cell anergy","volume":"21","author":"Schwartz","year":"2003","journal-title":"Annu Rev Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"608024","DOI":"10.3389\/fimmu.2020.608024","article-title":"Beyond T-cells: functional characterization of CTLA-4 expression in immune and non-immune cell types","volume":"11","author":"Oyewole-Said","year":"2020","journal-title":"Front Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.it.2014.12.001","article-title":"Confusing signals: recent progress in CTLA-4 biology","volume":"36","author":"Walker","year":"2015","journal-title":"Trends Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/all.12911","article-title":"Ontogeny of human IgE-expressing B cells and plasma cells","volume":"72","author":"Ramadani","year":"2017","journal-title":"Allergy."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e20220964","DOI":"10.1084\/jem.20220964","article-title":"cell receptor ligation induces IgE plasma cell elimination","volume":"220","author":"Wade-Vallance","year":"2023","journal-title":"J Exp Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.4049\/jimmunol.1090085","article-title":"Staying alive: T cell costimulation, CD28, and Bcl-xL","volume":"185","author":"Watts","year":"2010","journal-title":"J Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jaci.2004.03.050","article-title":"CTLA-4 polymorphisms in allergy and asthma and the TH1\/TH2 paradigm","volume":"114","author":"Munthe-Kaas","year":"2004","journal-title":"J Allergy Clin Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e42062","DOI":"10.1371\/journal.pone.0042062","article-title":"Cytotoxic T-lymphocyte associated antigen 4 polymorphisms and asthma risk: a meta-analysis","volume":"7","author":"Nie","year":"2012","journal-title":"PLoS ONE."},{"key":"B30","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1164\/rccm.201207-1205OC","article-title":"A randomized controlled trial to evaluate inhibition of T-cell costimulation in allergen-induced airway inflammation","volume":"187","author":"Parulekar","year":"2013","journal-title":"Am J Respir Crit Care Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"589641","DOI":"10.3389\/fimmu.2020.589641","article-title":"Revisiting T cell tolerance as a checkpoint target for cancer immunotherapy","volume":"11","author":"N\u00fcssing","year":"2020","journal-title":"Front Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"6894","DOI":"10.4049\/jimmunol.178.11.6894","article-title":"The CD28\/CTLA-4-B7 signaling pathway is involved in both allergic sensitization and tolerance induction to orally administered peanut proteins","volume":"178","author":"van Wijk","year":"2007","journal-title":"J Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.jaci.2022.02.024","article-title":"A mouse model of the LEAP study reveals a role for CTLA-4 in preventing peanut allergy induced by environmental peanut exposure","volume":"150","author":"Krempski","year":"2022","journal-title":"J Allergy Clin Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1165\/ajrcmb.17.3.2679","article-title":"Murine CTLA4-IgG treatment inhibits airway eosinophilia and hyperresponsiveness and attenuates IgE upregulation in a murine model of allergic asthma","volume":"17","author":"Van Oosterhout","year":"1997","journal-title":"Am J Respir Cell Mol Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1084\/jem.185.9.1671","article-title":"Costimulation through B7-2 (CD86) is required for the induction of a lung mucosal T helper cell 2 (TH2) immune response and altered airway responsiveness","volume":"185","author":"Tsuyuki","year":"1997","journal-title":"J Exp Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.4049\/jimmunol.158.5.2042","article-title":"B7-CD28\/CTLA-4 costimulatory pathways are required for the development of T helper cell 2-mediated allergic airway responses to inhaled antigens","volume":"158","author":"Keane-Myers","year":"1997","journal-title":"J Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1172\/JCI119093","article-title":"Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model","volume":"98","author":"Krinzman","year":"1996","journal-title":"J Clin Invest."},{"key":"B38","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/cei.12041","article-title":"Cytotoxic T lymphocyte antigen 4-immunoglobulin G is a potent adjuvant for experimental allergen immunotherapy","volume":"172","author":"Maazi","year":"2013","journal-title":"Clin Exp Immunol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/j.jaci.2012.10.017","article-title":"Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report","volume":"130","author":"Sampson","year":"2012","journal-title":"J Allergy Clin Immunol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1001\/jama.2017.16591","article-title":"Effect of varying doses of epicutaneous immunotherapy vs. placebo on reaction to peanut protein exposure among patients with peanut sensitivity: a randomized clinical trial","volume":"318","author":"Sampson","year":"2017","journal-title":"J Am Med Assoc."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1016\/j.jaci.2021.12.789","article-title":"Updating the CoFAR grading scale for systemic allergic reactions in food allergy","volume":"149","author":"Chinthrajah","year":"2022","journal-title":"J Allergy Clin Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1016\/S0140-6736(19)31793-3","article-title":"Sustained outcomes in a large double-blind, placebo-controlled, randomized phase 2 study of peanut immunotherapy","volume":"394","author":"Chinthrajah","year":"2019","journal-title":"Lancet Lond Engl."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13075-017-1488-5","article-title":"Abatacept used in combination with non-methotrexate disease-modifying antirheumatic drugs: a descriptive analysis of data from interventional trials and the real-world setting","volume":"20","author":"Alten","year":"2018","journal-title":"Arthritis Res Ther."},{"key":"B44","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.jaci.2016.05.027","article-title":"Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective","volume":"139","author":"Vickery","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1016\/j.jaci.2019.07.030","article-title":"Long-term sublingual immunotherapy for peanut allergy in children: clinical and immunologic evidence of desensitization","volume":"144","author":"Kim","year":"2019","journal-title":"J Allergy Clin Immunol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1198173\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T08:31:37Z","timestamp":1687941097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1198173\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,28]]},"references-count":45,"alternative-id":["10.3389\/fmed.2023.1198173"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2023.1198173","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,28]]},"article-number":"1198173"}}