PB0546 - The lower double negative T cells proportion predicted the better high-titer inhibitors eradication outcomes of immune tolerance induction

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Zhengping Li, Medical Doctor in progress

M.D. in progress
zhengp_li@163.com
Beijing, Beijing, China (People's Republic)

Co-Author(s)

Zhenping Chen

Associate professor
Hematologic Diseases Laboratory, Hematology Center, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, ChinaChildren’s Health, Beijing, 100045, China
Beijing, Beijing, China (People's Republic)
Runhui Wu, PhD, MD

Professor
Department of Hematology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China
Beijing, Beijing, China (People's Republic)

Background: The immunologic indicators to predict immune tolerance induction (ITI) outcomes still lack.

Aims: To investigate the role of lymphocyte subsets in ITI outcomes for severe hemophilia A (SHA) children with high-titer inhibitors.

Methods: From January 2022 to September 2023, a prospective single-center cohort study was conducted on SHA children age ≤8 years, with peak historical inhibitor-titer 5 – 200 Bethesda Units (BU)/mL, received ITI treatment [Factor (F)VIII 50-100IU/kg every other day-every day] using recombinant FVIII (SCT800). Flow cytometry analysis was performed to evaluate the proportions and numbers of peripheral lymphocytes, including T cell subsets, B cell subsets and NK cells before ITI. The outcomes of ITI were assessed at ≥24 months follow-up after ITI-start. Success: negative inhibitor-titer and FVIII recovery ≥66% of expected at the time of analysis.

Results: Total 27 patients were enrolled, including 19 (70.4%) in success (S)-group, and rest in non-success (NS)-group. There was no difference in the clinical baseline variables and ITI regimens between S-group and NS-group.
As shown in table 1, only the proportion of T cell receptor (TCR)-αβ+ CD4− CD8− double negative T cells (DNTs) in total lymphocyte was lower in the S-group compared to that in the NS-group (1.6% vs. 2.4%, p = 0.007). There was a decreasing trend for absolute counts of DNTs in S-group compared with NS-group (54/uL vs. 211/uL, p = 0.192).
The cut-off value for predicting ITI outcomes based on DNTs proportion was 2.25% [area under ROC-curve, 0.78; sensitivity: 0.938, specificity: 0.545]. That is the TCR-αβ+ DNTs proportion in total lymphocytes of ≤2.25% was associated with higher ITI success rate (Figure 1).
Through the linear regression model, we discovered there was not relationship between lymphocyte subsets (neither proportion nor absolute value) and time to success.

Conclusion(s): In conclusion, lower proportion of TCR-αβ+ DNTs in total lymphocytes leads to higher ITI success rate.