We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Technopath Clinical Diagnostics

Download Mobile App


ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.
05 Sep 2020 - 09 Sep 2020
Virtual Venue

Genetics Affect Risk of Developing Factor VIII Inhibitors

By LabMedica International staff writers
Posted on 06 Sep 2019
Print article
Image: Risk stratification integrating genetic data for factor VIII inhibitor development in patients with severe hemophilia (Photo courtesy of Paris-Saclay University).
Image: Risk stratification integrating genetic data for factor VIII inhibitor development in patients with severe hemophilia (Photo courtesy of Paris-Saclay University).
For severe hemophilia A (HA) patients, the current standard of care includes regular prophylactic infusions of factor VIII (FVIII) products in order to prevent spontaneous bleeds or on demand infusions to treat bleeds.

Many factors, such as patient-, disease- or product-related, could influence the potential risk for immunogenicity of biotherapeutics, but the relative contributions of these factors to the development of neutralizing antibodies is currently not completely understood. Several risk factors of inhibition against FVIII products are well recognized, such as factor VIII gene (F8) mutation type.

An international group of scientists led by the Paris-Saclay University (Villejuif, France) analyzed data from patients with severe hemophilia A from two German centers in Bonn and Frankfurt, who were recruited for the European ABIRISK tranSMART database. They investigated clinical and genetic components behind factor VIII inhibitors’ development, looking specifically to immune-related genes. In all, 593 patients with severe HA from the Bonn database and 79 from the Frankfurt database were included in the present study.

HLA class II (HLA-DRB1, HLA-DQB1) typing was performed by polymerase chain reaction (PCR) sequence-specific primer (SSP) methodology. Single Nucleotide Polymorphism (SNP) variants for IL-10 1082A>G (rs1800896), CTLA4 CT60A>G (rs3087243), TNF 308G>A (rs1800629), CD32 500 A>G (rs1801274), MAPK9 (rs4147385) were genotyped. For the CD86 gene, four biallelic SNPs were investigated: rs2715267 in the promoter region, rs2681417 in the exon 4 region, rs1129055 in the exon 7 region and rs2681401 in the untranslated transcribed region (UTR).

In total, 586 patients from Bonn were analyzed, of which 113 (19%) developed inhibitors, and 79 from Frankfurt, of which 32 patients (41%) developed inhibitors. The analysis revealed that patients from Bonn with a familial history of inhibitor development had 5.94 times higher risk of developing inhibitors, compared to patients without a family history of an immune response against factor VIII. Familial history was not available for the Frankfurt patients. Although not significant in the two centers’ data, the team observed that patients with a blood type other than O were 1.46 more likely to develop inhibitors.

On an analysis of in 142 patients from the Bonn database, they showed that patients with a specific HLA haplotype (called HLA-DRB1*15), and with a particular SNP in the IL-10 gene, had higher risk for developing inhibitors. Of 30 patients in this group, 23 developed an immune response against factor VIII. Patients negative for the haplotypes HLA-DRB1*15 and HLA-DQB1*02, and for certain SNPs in the gene, had the lowest risk, with only four of 36 patients within this subgroup developing inhibitors.

The authors concluded that the final optimal hybrid tree-based model distinguishes two groups of patients: a high-risk group for immunogenicity with positive HLA-DRB1*15 and IL-10 genotype G/A and A/A, a low-risk group for immunogenicity with negative HLADRB1*15/ HLADQB1*02 and CD86 genotype T/T and G/T. The study was originally published on June 13, 2019, in the journal PLOS ONE.

Related Links:
Paris-Saclay University

Print article


Molecular Diagnostics

view channel
Image: Structure of the ACE2 (angiotensin-converting enzyme 2) protein (Photo courtesy of Wikimedia Commons)

Elevated Angiotensin 1–7/Angiotensin II Ratio Predicts Favorable Outcomes in Patients with Heart Failure with Potential Link to COVID-19 Patients

A high ratio of angiotensin 1-7 to angiotensin II (Ang 1–7/Ang II ratio), was found to be an independent and incremental predictor of beneficial outcomes, higher survival rate, and decreased hospitalization... Read more

Industry News

view channel
Image: ChemWell RPR Analyzer (Photo courtesy of Awareness Technology, Inc.)

Awareness Technology Announces ChemWell RPR Analyzer - The Most Significant Innovation in Syphilis Testing in Last 30 Years

Awareness Technology, Inc. (Palm City, FL, USA) has announced the most significant innovation in syphilis testing in the last 30 years with the launch of the ChemWell RPR automated nontreponemal analyzer... Read more
Copyright © 2000-2020 Globetech Media. All rights reserved.