PB0247 - Exploring Predictive Biomarkers for inhibitor development in Hemophilia A

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Meng-Ni Fan

Research Scientist
Seattle Children's Research Institute
Seattle, Washington, United States

Co-Author(s)

TS

Tangliang Shen

PhD student
Georgia State University
Atlanta, Georgia, United States
XC

Xiaohe Cai

Research Scientist
Seattle Children's Research Institute
Seattle, Washington, United States
Ting-Yen Chao

Research Scientist
Seattle Children's Research Institute
Everett, Washington, United States
MM

Marilyn J. Manco-Johnson

Professor
Hemophilia & Thrombosis Center, University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
WX

Weidong Xiao

Professor
Indiana University
Indianapolis, Indiana, United States
Barbara A. Konkle

Professor of Medicine
Washington Center for Bleeding Disorders and the University of Washington, Seattle, WA, USA
Seattle, Washington, United States
LL

Lei Li

Assistant Professor
Georgia State University
Atlanta, Georgia, United States
CM

Carol H. Miao

Principal Investigator
Seattle Children's Research Institute
Seattle, Washington, United States

Background: Inhibitor formation is a major challenge for hemophilia A (HA) treatment. While the risk is highest within 15 exposure days, patients are at risk throughout their lifetime. Despite known risk factors, the absence of biomarkers impedes proactive prevention.

Aims: We aim to identify biomarkers within inflammatory cytokines and glycosylation-related parameters, which has extensively explored for biomarker discovery of various diseases including cancers

Methods: Levels of 10 inflammatory cytokines were assessed from 60 HA patients, and 23 healthy donors. Additionally, 20 glycans in plasma were analyzed by using MALDI-TOF MS/MS and the various glycan ratios were calculated based on the characteristics of glycans. HA samples were categorized into inhibitor-negative (InhNeg, BU < 0.6, n = 26) and inhibitor-positive (InhPos, BU ≥ 0.6, n = 34). The inhibitor-positive samples were further divided into good risk ( < 10 BU, n = 14) and poor risk (≥ 10 BU, n = 20) groups based on immune tolerance induction therapy prognosis

Results: Adjusted odds ratios revealed a 2.84-fold (95% CI: 1.45-8.48; p = 0.021) increased likelihood of inhibitor development for elevated G-CSF, 1.50-fold (95% CI: 1.14-2.42; p = 0.069) for IL-6, and a 0.28-fold (95% CI: 0.10-0.61; p = 0.006) decreased likelihood for IL-10 in HA patients. Among InhPos HA patients, the poor risk group exhibited significantly higher levels of G-CSF, IL-2, IL-6, IL-8, and IL-10 (p-value < 0.05, ANOVA). Additionally, adult InhPos group had significantly higher complex glycan and reduced hybrid glycan ratios, while pediatric InhPos group showed an increased sialic acid ratio.

Conclusion(s): Elevated G-CSF and IL-6 levels, coupled with decreased IL-10, were associated with inhibitor presence. Ratios of hybrid and complex glycans in adults, and sialic acid in pediatric HA patients, hold promise for identifying the risk of inhibitor development.