Factor IX antibodies and tolerance in hemophilia B in the Nordic countries – The impact of F9 variants and complications
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Introduction: The development of inhibitory antibodies (inhibitors) in persons with hemophilia B (PwHB) causes significant morbidity. Data on the impact of the F9 variant and immune tolerance induction (ITI) outcome are limited. The aim of this study was to investigate the presence of neutralizing and non-neutralizing antibodies (NNA) in severe hemophilia B (HB) and to evaluate ITI outcome and complications in relation to the pathogenic F9 variant. Materials and methods: Persons with severe HB in the Nordic countries were enrolled and information on F9 variants, inhibitors, ITI and complications were collected. Analyses of anti-FIX antibodies with a fluorescence-immunoassay (xFLI) and an ELISA method were conducted. Results: Seventy-nine PwHB were enrolled. Null variants were seen in 33 (42 %) PwHB and 12 (15 %) had a current or former inhibitor. Eleven (92 %) of the inhibitor patients had experienced allergic manifestations and three (25 %) nephrotic syndrome. Of 10 PwHB with at least one ITI attempt, eight (80 %) were considered tolerant at enrolment. Immunosuppression was included in seven of eight successful or partially successful attempts. Five PwHB had at least one ITI failure before a successful or partially successful ITI. No NNA could be identified. Conclusion: A high proportion of severe F9 gene defects among persons with severe HB in the Nordic countries may explain the observed relatively high prevalence of inhibitors. ITI success was independent of the F9 variant and attained despite allergic manifestations and previous ITI failures. Inclusion of immunosuppression tentatively enhances the chances of ITI success. No NNA were observed.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Thrombosis Research |
| Vol/bind | 217 |
| Sider (fra-til) | 22-32 |
| Antal sider | 11 |
| ISSN | 0049-3848 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
JA has received research grants from Sobi, CSL Behring, Takeda/Shire, and Bayer and speaker's fee and consultant's fee for Octapharma, NovoNordisk, Pfizer, Bayer, Sobi, CSL Behring, Takeda/Shire, BioMarin, Uniqure, and Spark Therapeutics.
Funding Information:
SR has received research grants from the Childhood Cancer Foundation, PedNet and Stockholm County Council, is a member of steering committee for Roche and investigator in clinical trials promoted by Roche, Novo Nordisk and Sobi.
Funding Information:
KK has received research grants from CSL Behring, Stockholm, Sweden. FB has received honoraria as a member of an advisory board and/or speaker from Sobi, Shire/Takeda, Novo Nordisk, Bayer, Roche, UniQure, Octapharma, BioMarin and Pfizer. MB was supported by funds from Stockholm County Council. EF has received honorarium as a speaker for Shire, Roche, Sobi and Takeda. PAH has acted as a paid consultant to Bayer, Shire, Novo Nordisk, Octapharma, CSL Behring, Pfizer and Sobi including lectures. RL has been a member of advisory boards for Sobi, CSL Behring, Takeda, BioMarin, Novo Nordisk, Pfizer, Roche and Bayer. VN has received research grant from CSL Behring, Stockholm, Sweden. SR has received research grants from the Childhood Cancer Foundation, PedNet and Stockholm County Council, is a member of steering committee for Roche and investigator in clinical trials promoted by Roche, Novo Nordisk and Sobi. KS has received speaker fees from Octapharma, Sobi, Shire and Novo Nordisk and has been scientific advisory board member for Novo Nordisk, Sobi and BioMarin. NGA has served as a speaker and/or on advisory boards for Bayer, CSL Behring, Octapharma and Sobi. EB has received research grants and paid consultancy from CSL Behring, Stockholm, Sweden. JA has received research grants from Sobi, CSL Behring, Takeda/Shire, and Bayer and speaker's fee and consultant's fee for Octapharma, NovoNordisk, Pfizer, Bayer, Sobi, CSL Behring, Takeda/Shire, BioMarin, Uniqure, and Spark Therapeutics. MM stated that she had no interests, which might be perceived as posing a conflict or bias.
Publisher Copyright:
© 2022
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