OC 50.4 - Maternal microchimerism promote FVIII tolerance in haemophilia A children with inhibitor under ITI

Tuesday, June 27, 2023

11:30 – 11:45 ET

Room: 516

Session Available As: Live-Stream and On-Demand

Co-Author(s)

Zekun Li, PhD

Doctor of Medicine
Hemophilia Comprehensive Care Center, Hematology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health
Beijing, Beijing, China (People's Republic)

Co-Author(s)

Yl

Yeling lu

Laboratory physician
Faculty of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Shanghai, Shanghai, China (People's Republic)

Presenting Author(s)

Zhenping CHEN, MD

Beijing Children’s Hospital, Capital Medical University
Beijing, Beijing, China (People's Republic)

Co-Author(s)

JD

Jing Dai

senior scientist
Shanghai Jiaotong University School of Medicine affiliated Ruijin Hospital
shanghai, Shanghai, China (People's Republic)
WW

Wenman Wu

researcher
Department of Clinical Laboratory Medicine
Shanghai, Shanghai, China (People's Republic)
XW

Xuefeng Wang

Laboratory physician
Faculty of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China (People's Republic)
RW

Runhui Wu

Director and Physician in Chief
Beijing Children’s Hospital, Capital Medical University, Beijing, China
Beijing, Beijing, China (People's Republic)

Background: The major treatment related complication of haemophilia A is the development of neutralizing anti-factor VIII (FVIII) antibodies (inhibitor) with a successful eradication rate of 60-90% by immune tolerance induction (ITI). Maternal microchimerism (MMc) was found to protect inhibitor development, but it’s role in the inhibitor eradication is still unclear.

Aims: We conducted this study to evaluate the inhibitor feature and ITI outcome influenced by MMc.

Methods: This study recruited patient (with mother pairs) with inhibitor who completed low-dose ITI (FVIII 50IU/kg. QoD). Three SNPs on X chromosome were selected as markers for individual DNA identification and MMc was examined by droplet digital PCR. Cox regression to identify the prognostic factors of ITI.

Results: Totally 103 cases underwent ITI more than 24m were enrolled, 89 maternal parents were informative for the microchimerism analysis. Among 89 cases, 20 (22.5%) were tested for MMc+. Baseline characteristic are all comparable between MMc+ and MMc- patients. The patients with MMc+ had a 7.4-fold increase in showing downward trend of inhibitor directly (Odds ratio [OR] 7.367, 95% confidence interval [CI] 1.975-27.478), a 4.9-fold increase in presenting a low response of inhibitor during ITI (＜10BU) (OR 4.887, 95%CI 1.693-14.104). Patients with MMc+ achieved a higher success rate (90% vs 71%) and taken a shorter time (3.7 vs 9.9 months) to success than MMc- patients. For those with high response of inhibitor in historical (≥10BU), MMc+ (Hazard ratio [HR] 2.619, 95%CI 1.276-5.372) and peak inhibitor during ITI ≥50BU (HR 0.344, 95%CI 0.185-0.638) were the good and poor prognostic factor of ITI success.

Conclusion(s): Maternal microchimerism promote FVIII tolerance in haemophilia A patient with inhibitor under ITI.

Learning Objectives:

How to use digital PCR technology to detect maternal microchimerism.
Clinical manifestation of FVIII inhibitor patients with maternal microchimerism.
Potential effect of maternal microchimerism to promote FVIII tolerance.