Survey of the anti–factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay

Hemophilia Inhibitor Research Study Investigators

doi:10.1111/jth.13438

Survey of the anti–factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay

Hemophilia Inhibitor Research Study Investigators

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Abstract

Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti–factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen–Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB. Summary: Background Hemophilia B (HB) is an inherited bleeding disorder caused by the absence or dysfunction of coagulation factor IX (FIX). A subset of patients who have HB develop neutralizing alloantibodies (inhibitors) against FIX after infusion therapy. HB prevalence and the proportion of patients who develop inhibitors are much lower than those for hemophilia A (HA), which makes studies of inhibitors in patients with HB challenging due to the limited availability of samples. As a result, there is a knowledge gap regarding HB inhibitors. Objective Evaluate the largest group of patients with inhibitor-positive HB studied to date to assess the relationship between anti-FIX antibody profiles and inhibitor formation. Methods A fluorescence immunoassay was used to detect anti-FIX antibodies in plasma samples from 37 patients with HB. Results Assessments of antibody profiles showed that anti-FIX IgG_1-4, IgA, and IgE were detected significantly more often in patients with a positive Nijmegen–Bethesda assay (NBA). All NBA-positive samples were positive for IgG₄. Anti-FIX IgG₄ demonstrated a strong correlation with the NBA, while correlations were significant, yet more moderate, for anti-FIX IgG_1-2 and IgA. Conclusions The anti-FIX antibody profile in HB patients who develop inhibitors is diverse and correlates well with the NBA across immunoglobulin (sub)class, and anti-FIX IgG₄ is particularly relevant to functional inhibition. The anti-FIX fluorescence immunoassay may serve as a useful tool to confirm the presence of antibodies in patients who have low positive NBA results and to more clearly define, predict, and treat alloantibody formation against FIX.

Original language	English (US)
Pages (from-to)	1931-1940
Number of pages	10
Journal	Journal of Thrombosis and Haemostasis
Volume	14
Issue number	10
DOIs	https://doi.org/10.1111/jth.13438
State	Published - Oct 1 2016

All Science Journal Classification (ASJC) codes

Hematology

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10.1111/jth.13438

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@article{663ed73b62f54ce1966a2091db059634,

title = "Survey of the anti–factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay",

abstract = "Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti–factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen–Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB. Summary: Background Hemophilia B (HB) is an inherited bleeding disorder caused by the absence or dysfunction of coagulation factor IX (FIX). A subset of patients who have HB develop neutralizing alloantibodies (inhibitors) against FIX after infusion therapy. HB prevalence and the proportion of patients who develop inhibitors are much lower than those for hemophilia A (HA), which makes studies of inhibitors in patients with HB challenging due to the limited availability of samples. As a result, there is a knowledge gap regarding HB inhibitors. Objective Evaluate the largest group of patients with inhibitor-positive HB studied to date to assess the relationship between anti-FIX antibody profiles and inhibitor formation. Methods A fluorescence immunoassay was used to detect anti-FIX antibodies in plasma samples from 37 patients with HB. Results Assessments of antibody profiles showed that anti-FIX IgG1-4, IgA, and IgE were detected significantly more often in patients with a positive Nijmegen–Bethesda assay (NBA). All NBA-positive samples were positive for IgG4. Anti-FIX IgG4 demonstrated a strong correlation with the NBA, while correlations were significant, yet more moderate, for anti-FIX IgG1-2 and IgA. Conclusions The anti-FIX antibody profile in HB patients who develop inhibitors is diverse and correlates well with the NBA across immunoglobulin (sub)class, and anti-FIX IgG4 is particularly relevant to functional inhibition. The anti-FIX fluorescence immunoassay may serve as a useful tool to confirm the presence of antibodies in patients who have low positive NBA results and to more clearly define, predict, and treat alloantibody formation against FIX.",

author = "{Hemophilia Inhibitor Research Study Investigators} and B. Boylan and Rice, {A. S.} and Neff, {A. T.} and Manco-Johnson, {M. J.} and Kempton, {C. L.} and Miller, {C. H.} and Abshire, {T. C.} and A. Dunn and Bockenstedt, {P. L.} and Brettler, {D. B.} and {Di Paola}, {J. A.} and M. Radhi and Lentz, {S. R.} and G. Massey and Barrett, {J. C.} and Shapiro, {A. D.} and M. Tarantino and Wicklund, {B. M.} and C. Knoll and Escobar, {M. A.} and Eyster, {M. E.} and Gill, {J. C.} and C. Leissinger and H. Yaish",

note = "Publisher Copyright: {\textcopyright} 2016 International Society on Thrombosis and Haemostasis",

year = "2016",

month = oct,

day = "1",

doi = "10.1111/jth.13438",

language = "English (US)",

volume = "14",

pages = "1931--1940",

journal = "Journal of Thrombosis and Haemostasis",

issn = "1538-7933",

publisher = "Elsevier B.V.",

number = "10",

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TY - JOUR

T1 - Survey of the anti–factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay

AU - Hemophilia Inhibitor Research Study Investigators

AU - Boylan, B.

AU - Rice, A. S.

AU - Neff, A. T.

AU - Manco-Johnson, M. J.

AU - Kempton, C. L.

AU - Miller, C. H.

AU - Abshire, T. C.

AU - Dunn, A.

AU - Bockenstedt, P. L.

AU - Brettler, D. B.

AU - Di Paola, J. A.

AU - Radhi, M.

AU - Lentz, S. R.

AU - Massey, G.

AU - Barrett, J. C.

AU - Shapiro, A. D.

AU - Tarantino, M.

AU - Wicklund, B. M.

AU - Knoll, C.

AU - Escobar, M. A.

AU - Eyster, M. E.

AU - Gill, J. C.

AU - Leissinger, C.

AU - Yaish, H.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti–factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen–Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB. Summary: Background Hemophilia B (HB) is an inherited bleeding disorder caused by the absence or dysfunction of coagulation factor IX (FIX). A subset of patients who have HB develop neutralizing alloantibodies (inhibitors) against FIX after infusion therapy. HB prevalence and the proportion of patients who develop inhibitors are much lower than those for hemophilia A (HA), which makes studies of inhibitors in patients with HB challenging due to the limited availability of samples. As a result, there is a knowledge gap regarding HB inhibitors. Objective Evaluate the largest group of patients with inhibitor-positive HB studied to date to assess the relationship between anti-FIX antibody profiles and inhibitor formation. Methods A fluorescence immunoassay was used to detect anti-FIX antibodies in plasma samples from 37 patients with HB. Results Assessments of antibody profiles showed that anti-FIX IgG1-4, IgA, and IgE were detected significantly more often in patients with a positive Nijmegen–Bethesda assay (NBA). All NBA-positive samples were positive for IgG4. Anti-FIX IgG4 demonstrated a strong correlation with the NBA, while correlations were significant, yet more moderate, for anti-FIX IgG1-2 and IgA. Conclusions The anti-FIX antibody profile in HB patients who develop inhibitors is diverse and correlates well with the NBA across immunoglobulin (sub)class, and anti-FIX IgG4 is particularly relevant to functional inhibition. The anti-FIX fluorescence immunoassay may serve as a useful tool to confirm the presence of antibodies in patients who have low positive NBA results and to more clearly define, predict, and treat alloantibody formation against FIX.

AB - Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti–factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen–Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB. Summary: Background Hemophilia B (HB) is an inherited bleeding disorder caused by the absence or dysfunction of coagulation factor IX (FIX). A subset of patients who have HB develop neutralizing alloantibodies (inhibitors) against FIX after infusion therapy. HB prevalence and the proportion of patients who develop inhibitors are much lower than those for hemophilia A (HA), which makes studies of inhibitors in patients with HB challenging due to the limited availability of samples. As a result, there is a knowledge gap regarding HB inhibitors. Objective Evaluate the largest group of patients with inhibitor-positive HB studied to date to assess the relationship between anti-FIX antibody profiles and inhibitor formation. Methods A fluorescence immunoassay was used to detect anti-FIX antibodies in plasma samples from 37 patients with HB. Results Assessments of antibody profiles showed that anti-FIX IgG1-4, IgA, and IgE were detected significantly more often in patients with a positive Nijmegen–Bethesda assay (NBA). All NBA-positive samples were positive for IgG4. Anti-FIX IgG4 demonstrated a strong correlation with the NBA, while correlations were significant, yet more moderate, for anti-FIX IgG1-2 and IgA. Conclusions The anti-FIX antibody profile in HB patients who develop inhibitors is diverse and correlates well with the NBA across immunoglobulin (sub)class, and anti-FIX IgG4 is particularly relevant to functional inhibition. The anti-FIX fluorescence immunoassay may serve as a useful tool to confirm the presence of antibodies in patients who have low positive NBA results and to more clearly define, predict, and treat alloantibody formation against FIX.

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U2 - 10.1111/jth.13438

DO - 10.1111/jth.13438

M3 - Article

C2 - 27501440

AN - SCOPUS:84987829329

SN - 1538-7933

VL - 14

SP - 1931

EP - 1940

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

IS - 10

ER -

Survey of the anti–factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay

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