{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:18:46Z","timestamp":1787635126933,"version":"build-2736575974"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Predictors for the successful eradication of neutralizing anti-FVIII alloantibodies (inhibitors) in hemophilia A patients receiving immune tolerance induction (ITI) therapy remain limited. Maternal microchimerism (MMc) showed potential to protect hemophilia A patients from inhibitor development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigated the role of MMc in ITI therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients\/Methods<\/jats:title>\n                    <jats:p>This observational study enrolled 121 pediatric with hemophilia A and inhibitors. MMc was determined using droplet digital PCR. Low-dose ITI (FVIII ~50IU\/kg every other day) was administered, with adjunctive rituximab given to patients with higher risk clinical features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 101 patients evaluable for MMc, 88 completed ITI, 18 were MMc positive (MMc+) and 70 were MMc negative (MMc-). Success was achieved in 75 (85.2%) patients, including 16 of 18 MMc+ patients (88.9%) and 59 of 70 MMc- patients (84.3%). Compared with MMc- patients, MMc+ patients had a lower peak inhibitor during ITI (median, 5.3 vs. 37.8 BU\/ml,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.029), less frequent rituximab use (27.8% vs. 61.4%;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.011), and a shorter time to ITI success (median, 3.0 vs 9.9 months;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.009). Multivariate Cox regression identified MMc+ (HR\u00a0=\u00a02.770), pre-ITI inhibitor &amp;lt;10BU\/ml (HR\u00a0=\u00a02.663), peak inhibitor during ITI&amp;lt;200BU\/ml (HR\u00a0=\u00a04.954) and non-large deletion\/duplication\n                      <jats:italic>F8<\/jats:italic>\n                      mutations (HR\u00a0=\u00a02.344) as independent predictors of shorter time to ITI success.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MMc was associated with more rapid ITI success in children with hemophilia A and inhibitors receiving low-dose ITI regimen, suggesting the potential role of MMc in facilitating the eradication of FVIII inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1921432","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:23:41Z","timestamp":1787631821000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal microchimerism accelerates immune tolerance induction to factor VIII in children with hemophilia A and FVIII inhibitors"],"prefix":"10.3389","volume":"17","author":[{"given":"Zekun","family":"Li","sequence":"first","affiliation":[{"name":"Hemophilia Comprehensive Care Center, Haematology Department, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeling","family":"Lu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Medicine Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Cai","sequence":"additional","affiliation":[{"name":"Blood Transfusion Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Pan","sequence":"additional","affiliation":[{"name":"Faculty of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Cai","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Evidence-based Medicine, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Cell and Gene Therapy Laboratory, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Ai","sequence":"additional","affiliation":[{"name":"Hemophilia Comprehensive Care Center, Haematology Department, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]},{"name":"Pediatrics Departments, National Key Discipline of Pediatrics, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hemophilia Comprehensive Care Center, Haematology Department, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]},{"name":"Pediatrics Departments, National Key Discipline of Pediatrics, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiulan","family":"Ding","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Medicine Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]},{"name":"Collaborative Innovation Center of Hematology, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenman","family":"Wu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Medicine Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]},{"name":"Faculty of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]},{"name":"Collaborative Innovation Center of Hematology, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Medicine Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]},{"name":"Faculty of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]},{"name":"Collaborative Innovation Center of Hematology, Shanghai Jiaotong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhui","family":"Wu","sequence":"additional","affiliation":[{"name":"Hemophilia Comprehensive Care Center, Haematology Department, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12730","article-title":"US guidelines for immune tolerance induction in patients with haemophilia a and inhibitors","volume":"21","author":"Valentino","year":"2015","journal-title":"Haemophilia"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011974","article-title":"Defining the impact of immune tolerance induction on clinically relevant outcomes in a US 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