Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay

the Hemophilia Inhibitor Research Study Investigators

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Summary: Background: The development of neutralizing antibodies, referred to as inhibitors, against factor VIII is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective: To assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods: A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results: Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2 or IgG4 correlated qualitatively and quantitatively with the presence of an FVIII inhibitor as determined with the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to being NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and had anti-FVIII IgG1 later developed an inhibitor, as compared with two of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions: These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing.

Original languageEnglish (US)
Pages (from-to)47-53
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2015

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Factor VIII
Hemophilia A
Immunoassay
Immunoglobulins
Fluorescence
Immunoglobulin G
Anti-Idiotypic Antibodies
History
Neutralizing Antibodies
Antibodies
Therapeutics

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

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title = "Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay",
abstract = "Summary: Background: The development of neutralizing antibodies, referred to as inhibitors, against factor VIII is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective: To assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods: A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results: Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2 or IgG4 correlated qualitatively and quantitatively with the presence of an FVIII inhibitor as determined with the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to being NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and had anti-FVIII IgG1 later developed an inhibitor, as compared with two of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions: These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing.",
author = "{the Hemophilia Inhibitor Research Study Investigators} and B. Boylan and Rice, {A. S.} and Miller, {C. H.} and Dunn, {A. L.} and Abshire, {T. C.} and Kempton, {C. L.} and Tarantino, {M. D.} and Brettler, {D. B.} and Barrett, {J. C.} and Dunn, {A. L.} and Bockenstedt, {P. L.} and {Di Paola}, {J. A.} and M. Radhi and Lentz, {S. R.} and G. Massey and Neff, {A. T.} and Shapiro, {A. D.} and Wicklund, {B. M.} and Manco-Johnson, {M. J.} and C. Knoll and Escobar, {M. A.} and {Elaine Eyster}, M. and Gill, {J. C.} and C. Leissinger and H. Yaish",
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Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay. / the Hemophilia Inhibitor Research Study Investigators.

In: Journal of Thrombosis and Haemostasis, Vol. 13, No. 1, 01.01.2015, p. 47-53.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay

AU - the Hemophilia Inhibitor Research Study Investigators

AU - Boylan, B.

AU - Rice, A. S.

AU - Miller, C. H.

AU - Dunn, A. L.

AU - Abshire, T. C.

AU - Kempton, C. L.

AU - Tarantino, M. D.

AU - Brettler, D. B.

AU - Barrett, J. C.

AU - Dunn, A. L.

AU - Bockenstedt, P. L.

AU - Di Paola, J. A.

AU - Radhi, M.

AU - Lentz, S. R.

AU - Massey, G.

AU - Neff, A. T.

AU - Shapiro, A. D.

AU - Wicklund, B. M.

AU - Manco-Johnson, M. J.

AU - Knoll, C.

AU - Escobar, M. A.

AU - Elaine Eyster, M.

AU - Gill, J. C.

AU - Leissinger, C.

AU - Yaish, H.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Summary: Background: The development of neutralizing antibodies, referred to as inhibitors, against factor VIII is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective: To assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods: A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results: Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2 or IgG4 correlated qualitatively and quantitatively with the presence of an FVIII inhibitor as determined with the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to being NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and had anti-FVIII IgG1 later developed an inhibitor, as compared with two of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions: These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing.

AB - Summary: Background: The development of neutralizing antibodies, referred to as inhibitors, against factor VIII is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective: To assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods: A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results: Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2 or IgG4 correlated qualitatively and quantitatively with the presence of an FVIII inhibitor as determined with the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to being NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and had anti-FVIII IgG1 later developed an inhibitor, as compared with two of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions: These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing.

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