Evidence map›Paper›PMID 40502463›Full record

ArticleResearch and practice in thrombosis and haemostasis2025

Exploration of biomarkers for inhibitor development in persons with hemophilia A.

Meng-Ni Fan, Tangliang Shen, Barbara A Konkle, Xiaohe Cai, Ting-Yen Chao, Marilyn Manco-Johnson, Anna V Faino, Junping Zhang, Shumin Bao, Weidong Xiao and 2 more

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Article in Research and practice in thrombosis and haemostasis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Meng-Ni FanCenter for Immunity & Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.
Tangliang ShenDepartment of Chemistry, Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Barbara A KonkleDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Xiaohe CaiCenter for Immunity & Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.
Ting-Yen ChaoCenter for Immunity & Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.
Marilyn Manco-JohnsonDepartment of Pediatrics, Hemophilia and Thrombosis Center, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.
Anna V FainoCore for Biostatistics, Epidemiology and Analytics in Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Junping ZhangDepartment of Pediatrics, Indiana University, Indianapolis, Indiana, USA.
Shumin BaoDepartment of Chemistry, Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Weidong XiaoDepartment of Pediatrics, Indiana University, Indianapolis, Indiana, USA.
Lei LiDepartment of Chemistry, Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Carol H MiaoCenter for Immunity & Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.

Funding

Toward Safer Gene Therapy for Hemophilia AP01HL160472 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI Roland W. Herzog · 2022 to 2026
$15.1M
Temple Project 1: Genetic characterization of factor VIII Inhibitors and glydosylation patternsU54HL142019 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI LI, LEI, MIAO, CAROL H · 2018 to 2022
$6.9M
Ultrasound-mediated gene delivery to achieve therapeutic correction of hemophilia AR01HL151077 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI MIAO, CAROL H · 2020 to 2023
$3.2M
Gene Editing for Hemophilia A Treatment Using Lipid NanoparticlesR01HL169793 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI Carol H Miao · 2024 to 2026
$2.2M
Direct in vivo bone marrow transfer of lentiviral vector to correct hemophilia AR01HL123326 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI MIAO, CAROL H · 2016 to 2019
$1.9M
NHLBI NIH HHS P01 HL160472NHLBI NIH HHS R01 HL123326NHLBI NIH HHS R01 HL151077NHLBI NIH HHS R01 HL169793NHLBI NIH HHS U54 HL142019
6 · The paper itself

Abstract

Background: Inhibitor development remains a significant challenge for hemophilia A (HA) treatment. Cytokines and glycosylation play crucial roles in inducing and regulating immune responses. Cytokine and altered N-glycan profiles have the potential to be biomarkers in association with the presence of inhibitors in persons with HA. Objectives: We investigated the association of cytokine and plasma N-glycan profiles with inhibitor presence. Methods: In 60 persons with HA and 23 controls, we analyzed 10 cytokines and used multivariable regression to assess their association with inhibitor presence. Given the challenges of validating these findings in previously untreated patients, we employed an HA mouse model to explore the association between cytokine levels and inhibitors. We also examined the correlation between plasma N-glycan profiles and inhibitors in persons with HA, analyzing adult and pediatric groups separately due to age-dependent glycosylation. Results: Elevated granulocyte colony-stimulating factor and interleukin (IL) 6 levels, coupled with decreased IL-10, were significantly associated with inhibitor presence in multivariable regression analysis. High-titer inhibitor was observed in factor (F)VIII-treated mice experiencing chronic inflammation with increased levels of granulocyte colony-stimulating factor, IL-6, and macrophage inflammatory protein-1β, a murine IL-8 homolog, but not in those receiving FVIII alone, consistent with our clinical observations. Inhibitor-positive adult patients exhibited higher biantennary Conclusion: These findings highlight the association of inhibitor presence with altered plasma cytokine levels and

Indexed as

biomarkercytokineglycosylationhemophilia Ainhibitors

Identifiers

PMID40502463
PMCPMC12152330

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.