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@article{2379803,
author = {Paul, Helmut and Berg, Verena and Gangadharan, Bagirath and Bowen, Joel and LeBeau, Petra and Blatný, Jan and Male, Christoph and Radulescu, Vlad C and Diaz, Rosa and Mancuso, Maria Elisa and Brown, Deborah L and Reipert, Birgit M},
article_location = {AMSTERDAM},
article_number = {9},
doi = {http://dx.doi.org/10.1182/bloodadvances.2022007267},
keywords = {Hemophilia; FVIII inhibitor},
language = {eng},
issn = {2473-9529},
journal = {Blood advances},
title = {Prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures during FVIII inhibitor eradication},
url = {https://ashpublications.org/bloodadvances/article/7/9/1831/486551/Prospective-Hemophilia-Inhibitor-PUP-Study-reveals},
volume = {7},
year = {2023}
}
TY - JOUR
ID - 2379803
AU - Paul, Helmut - Berg, Verena - Gangadharan, Bagirath - Bowen, Joel - LeBeau, Petra - Blatný, Jan - Male, Christoph - Radulescu, Vlad C - Diaz, Rosa - Mancuso, Maria Elisa - Brown, Deborah L - Reipert, Birgit M
PY - 2023
TI - Prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures during FVIII inhibitor eradication
JF - Blood advances
VL - 7
IS - 9
SP - 1831-1848
EP - 1831-1848
PB - ELSEVIER
SN - 24739529
KW - Hemophilia
KW - FVIII inhibitor
UR - https://ashpublications.org/bloodadvances/article/7/9/1831/486551/Prospective-Hemophilia-Inhibitor-PUP-Study-reveals
N2 - Factor VIII (FVIII) inhibitor formation is a major clinical concern during replacement therapy in patients with hemophilia A. Immune tolerance induction (ITI) is the only therapeutic approach to attempt inhibitor eradication and establishment of long-term immune tolerance to FVIII. Hemophilia Inhibitor Previously Untreated Patient (PUP) Study (HIPS) was a prospective clinical trial to investigate changes in the immune system of PUPs with severe hemophilia A. Five patients who developed persistent FVIII inhibitors during HIPS entered an ITI extension arm (HIPS-ITI). During HIPS-ITI, inhibitor patients received ITI with the same FVIII product (a single source of recombinant, human full-length FVIII) used in HIPS until successful tolerance, declared failure, or a maximum of 2 years after HIPS-ITI enrollment, whichever came first. Blood samples and clinical data were collected monthly. Longitudinal FVIII-binding antibody signatures, associated binding specificities, and apparent affinities were determined for each patient at each sampling time point. ITI was successful or partially successful in 2 patients and failed in 3. Both groups presented with distinct FVIII-specific antibody signatures. ITI success required the disappearance of FVIII inhibitors, which was associated with the eradication or sustained titer minimization of high-affinity FVIII-specific antibodies, particularly of the immunoglobulin G1 (IgG1) and IgG4 subclasses. In contrast, ITI failure, as reflected by FVIII inhibitor persistence, was associated with persistent high-affinity FVIII-specific antibodies. Interestingly, 1 patient with partial ITI success and 1 patient with ITI failure developed apparent oligoreactive FVIII-binding antibodies during ITI. The explanation of the true nature of these antibodies requires more comprehensive follow-ups in future studies. This trial was registered at www.clinicaltrials.gov as #NCT01652027.
ER -
PAUL, Helmut, Verena BERG, Bagirath GANGADHARAN, Joel BOWEN, Petra LEBEAU, Jan BLATNÝ, Christoph MALE, Vlad C RADULESCU, Rosa DIAZ, Maria Elisa MANCUSO, Deborah L BROWN and Birgit M REIPERT. Prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures during FVIII inhibitor eradication. \textit{Blood advances}. AMSTERDAM: ELSEVIER, 2023, vol.~7, No~9, p.~1831-1848. ISSN~2473-9529. Available from: https://dx.doi.org/10.1182/bloodadvances.2022007267.
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