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Anti‐ A 2 and anti‐ A 1 domain antibodies are potential predictors of immune tolerance induction outcome in children with hemophilia A
Author(s) -
Lapalud P.,
Rothschild C.,
MathieuDupas E.,
Balicchi J.,
Gruel Y.,
Laune D.,
Molina F.,
Schved J. F.,
Granier C.,
LavigneLissalde G.
Publication year - 2015
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12846
Subject(s) - receiver operating characteristic , medicine , titer , antibody , confidence interval , predictive marker , immunology , cancer
Summary 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 .