# Project 2: GeorgiaCenter for the Investigation of Factor VIII Inhibitors and Glycosylation

> **NIH NIH U54** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $321,656

## Abstract

Summary 
Congenital Hemophilia A (HA) is an X-linked bleeding disorder due to a lack or dysfunction of coagulation FVIII 
(FVIII). Nearly 1 in 5,000 live male births are diagnosed with HA with 40% of whom involving of sporadic cases 
caused by de novo mutations. Plasma-derived FVIII (pdFVIII) and recombinant FVIII (rFVIII) are two major 
intravenous replacement therapy medicines for HA treatment. FVIII neutralizing antibodies, or inhibitors, occur 
in 25-30% of severe HA patients receiving protein replacement. These FVIII inhibitors essentially abolish the 
efficacy of the coagulant treatment, resulting in a considerable increase in the morbidity and healthcare cost. 
Although both rFVIII and pdFVIII share similar to identical primary amino acids, the risk of FVIII antibodies in 
previously untreated patients (PUPs) was reported to be higher following rFVIII treatment. As a glycoprotein, 
pdFVIII and rFVIII are different in glycosylation, a post-translation modification (PTM) that is capable of alter the 
immunogenicity of protein 
Therefore, in this project, we will develop a set of novel glycoanalysis toolset for FVIII inhibitors. In order to 
investigate the effect of the host glyco environment on FVIII, we propose to use FVIII closely associated VWF 
and FV as surrogate marker to show to potential effect on FVIII glycosylation in HA patients who developed FVIII 
inhibitors. Also, based on our developed MS-based approach, glycosylation pattern of total immunoglobulins, 
specific FVIII inhibitors, FV, VWF, and overall glycome changes of the host cell environment will be thoroughly 
characterized in a large number of HA patients’ samples, close attention to those undergone immune tolerance 
induction (ITI). The overall results obtained from this project will be significant for understanding the fundamental 
mechanism of FVIII immunogenicity.

## Key facts

- **NIH application ID:** 9930455
- **Project number:** 7U54HL142019-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Li Lei
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,656
- **Award type:** 7
- **Project period:** 2018-05-01 → 2020-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930455

## Citation

> US National Institutes of Health, RePORTER application 9930455, Project 2: GeorgiaCenter for the Investigation of Factor VIII Inhibitors and Glycosylation (7U54HL142019-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9930455. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*