Anti-A2 and anti-A1 domain antibodies are potential predictors of immune tolerance induction outcome in children with hemophilia A.
J Thromb Haemost
; 13(4): 540-7, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25603934
ABSTRACT
BACKGROUND:
Hemophilia A (HA) is a congenital bleeding disorder resulting from factor VIII deficiency. The most serious complication of HA management is the appearance of inhibitory antibodies (Abs) against injected FVIII concentrates. To eradicate inhibitors, immune tolerance induction (ITI) is usually attempted, but it fails in up to 30% of cases. Currently, no undisputed predictive marker of ITI outcome is available to facilitate the clinical decision.OBJECTIVES:
To identify predictive markers of ITI efficacy.METHODS:
The isotypic and epitopic repertoires of inhibitory Abs were analyzed in plasma samples collected before ITI initiation from 15 children with severe HA and high-titer inhibitors, and their levels were compared in the two outcome groups (ITI success [n = 7] and ITI failure [n = 8]). The predictive value of these candidate biomarkers and of the currently used indicators (inhibitor titer and age at ITI initiation, highest inhibitor titer before ITI, and interval between inhibitor diagnosis and ITI initiation) was then compared by statistical analysis (Wilcoxon test and receiver receiver operating characteristic [ROC] curve analysis).RESULTS:
Whereas current indicators seemed to fail in discriminating patients in the two outcome groups (ITI success or failure), anti-A1 and anti-A2 Ab levels before ITI initiation appeared to be good potential predictive markers of ITI outcome (P < 0.018). ROC analysis showed that anti-A1 and anti-A2 Abs were the best at discriminating between outcome groups (area under the ROC curve of > 0.875).CONCLUSION:
Anti-A1 and anti-A2 Abs could represent new promising tools for the development of ITI outcome prediction tests for children with severe HA.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Autoanticuerpos
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Factor VIII
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Inmunoglobulina G
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Coagulantes
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Hemofilia A
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Tolerancia Inmunológica
/
Inmunoterapia
/
Epítopos
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Child
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Child, preschool
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Humans
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Infant
País/Región como asunto:
Europa
Idioma:
En
Año:
2015
Tipo del documento:
Article