The prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures prior to FVIII inhibitor development
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F20%3A00117703" target="_blank" >RIV/00216224:14110/20:00117703 - isvavai.cz</a>
Alternative codes found
RIV/65269705:_____/20:00073270
Result on the web
<a href="https://watermark.silverchair.com/advancesadv2020002731.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAABA4wggQKBgkqhkiG9w0BBwagggP7MIID9wIBADCCA_AGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM4i795NteaBYi_4jtAgEQgIIDwbi72fPiY61518P6v9IR00njkDl3nDKG" target="_blank" >https://watermark.silverchair.com/advancesadv2020002731.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAABA4wggQKBgkqhkiG9w0BBwagggP7MIID9wIBADCCA_AGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM4i795NteaBYi_4jtAgEQgIIDwbi72fPiY61518P6v9IR00njkDl3nDKG</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/bloodadvances.2020002731" target="_blank" >10.1182/bloodadvances.2020002731</a>
Alternative languages
Result language
angličtina
Original language name
The prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures prior to FVIII inhibitor development
Original language description
Preventing factor VIII (FVIII) inhibitors following replacement therapies with FVIII products in patients with hemophilia A remains an unmet medical need. Better understanding of the early events of evolving FVIII inhibitors is essential for risk identification and the design of novel strategies to prevent inhibitor development. The Hemophilia Inhibitor Previously Untreated Patients (PUPs) Study (HIPS; www. clinicaltrials.gov #NCT01652027) is the first prospective cohort study to evaluate comprehensive changes in the immune system during the first 50 exposure days ( EDs) to FVIII in patients with severe hemophilia A. HIPS participants were enrolled prior to their first exposure to FVIII or blood products ("true PUPs") and were evaluated for different immunological and clinical parameters at specified time points during their first 50 EDs to a single source of recombinant FVIII. Longitudinal antibody data resulting from this study indicate that there are 4 subgroups of patients expressing distinct signatures of FVIII- binding antibodies. Subgroup 1 did not develop any detectable FVIII-binding immunoglobulin G (IgG) antibodies. Subgroup 2 developed nonneutralizing, FVIII-binding IgG1 antibodies, but other FVIII-binding IgG subclasses were not observed. Subgroup 3 developed transient FVIII inhibitors associated with FVIII-binding IgG1 antibodies, similar to subgroup 2. Subgroup 4 developed persistent FVIII inhibitors associated with an initial development of high-affinity, FVIII-binding IgG1 antibodies, followed by IgG3 and IgG4 antibodies. Appearance of FVIII-binding IgG3 was always associated with persistent FVIII inhibitors and the subsequent development of FVIII-binding IgG4. Some of the antibody signatures identified in HIPS could serve as candidates for early biomarkers of FVIII inhibitor development.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
BLOOD ADVANCES
ISSN
2473-9529
e-ISSN
2473-9537
Volume of the periodical
4
Issue of the periodical within the volume
22
Country of publishing house
SI - SLOVENIA
Number of pages
12
Pages from-to
5785-5796
UT code for WoS article
000593144300022
EID of the result in the Scopus database
2-s2.0-85097235672