Anaphylactic response to factor IX replacement therapy in haemophilia B patients: Complete gene deletions confer the highest risk

Erik C Thorland, J. B. Drost, J. M. Lusher, I. Warrier, A. Shapiro, M. A. Koerper, D. Dimichele, J. Westman, N. S. Key, S. S. Sommer

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Haemophilia B is an X-linked recessive coagulopathy due to mutations in the factor IX gene. Occasionally, patients receiving factor IX replacement therapy develop inhibiting antibodies to the factor IX protein, and it has been recently documented that a subset of these patients have had anaphylactic responses to factor IX replacement therapy in association with the development of inhibiting antibodies. To determine the relationship between mutation type and the risk of anaphylaxis, eight unrelated patients from families in whom anaphylaxis had occurred were genotyped. The mutations were compared to those in 550 haemophilia B patients and to those in 276 patients with clinically severe disease. Individuals with complete gene deletions were found to be at greatest risk for anaphylaxis, with an estimated risk of 26% or greater. Anaphylaxis was less likely to occur in patients with protein truncation mutations or partial gene deletions and least likely to occur with missense mutations. Genotypes can help physicians and patients anticipate the likelihood of anaphylaxis, a potentially life-threatening complication of factor IX replacement therapy. The very high risk of anaphylaxis associated with a complete gene deletion suggests that the lack of expression of a partial protein product may predispose to anaphylaxis and/or that the absence of a closely linked, codeleted gene enhances the anaphylactic immune response.

Original languageEnglish (US)
Pages (from-to)101-105
Number of pages5
JournalHaemophilia
Volume5
Issue number2
DOIs
StatePublished - 1999

Fingerprint

Hemophilia B
Factor IX
Gene Deletion
Anaphylaxis
Mutation
Therapeutics
Proteins
Antibodies
Missense Mutation
Genes
Genotype
Physicians

Keywords

  • Allergic reaction
  • Factor IX replacement
  • Genotype-phenotype interactions
  • Human factor IX mutations
  • Nonsense mutations
  • Total gene deletions

ASJC Scopus subject areas

  • Hematology

Cite this

Anaphylactic response to factor IX replacement therapy in haemophilia B patients : Complete gene deletions confer the highest risk. / Thorland, Erik C; Drost, J. B.; Lusher, J. M.; Warrier, I.; Shapiro, A.; Koerper, M. A.; Dimichele, D.; Westman, J.; Key, N. S.; Sommer, S. S.

In: Haemophilia, Vol. 5, No. 2, 1999, p. 101-105.

Research output: Contribution to journalArticle

Thorland, EC, Drost, JB, Lusher, JM, Warrier, I, Shapiro, A, Koerper, MA, Dimichele, D, Westman, J, Key, NS & Sommer, SS 1999, 'Anaphylactic response to factor IX replacement therapy in haemophilia B patients: Complete gene deletions confer the highest risk', Haemophilia, vol. 5, no. 2, pp. 101-105. https://doi.org/10.1046/j.1365-2516.1999.00303.x
Thorland, Erik C ; Drost, J. B. ; Lusher, J. M. ; Warrier, I. ; Shapiro, A. ; Koerper, M. A. ; Dimichele, D. ; Westman, J. ; Key, N. S. ; Sommer, S. S. / Anaphylactic response to factor IX replacement therapy in haemophilia B patients : Complete gene deletions confer the highest risk. In: Haemophilia. 1999 ; Vol. 5, No. 2. pp. 101-105.
@article{7f10e9633c774f4eabc1472c3845c587,
title = "Anaphylactic response to factor IX replacement therapy in haemophilia B patients: Complete gene deletions confer the highest risk",
abstract = "Haemophilia B is an X-linked recessive coagulopathy due to mutations in the factor IX gene. Occasionally, patients receiving factor IX replacement therapy develop inhibiting antibodies to the factor IX protein, and it has been recently documented that a subset of these patients have had anaphylactic responses to factor IX replacement therapy in association with the development of inhibiting antibodies. To determine the relationship between mutation type and the risk of anaphylaxis, eight unrelated patients from families in whom anaphylaxis had occurred were genotyped. The mutations were compared to those in 550 haemophilia B patients and to those in 276 patients with clinically severe disease. Individuals with complete gene deletions were found to be at greatest risk for anaphylaxis, with an estimated risk of 26{\%} or greater. Anaphylaxis was less likely to occur in patients with protein truncation mutations or partial gene deletions and least likely to occur with missense mutations. Genotypes can help physicians and patients anticipate the likelihood of anaphylaxis, a potentially life-threatening complication of factor IX replacement therapy. The very high risk of anaphylaxis associated with a complete gene deletion suggests that the lack of expression of a partial protein product may predispose to anaphylaxis and/or that the absence of a closely linked, codeleted gene enhances the anaphylactic immune response.",
keywords = "Allergic reaction, Factor IX replacement, Genotype-phenotype interactions, Human factor IX mutations, Nonsense mutations, Total gene deletions",
author = "Thorland, {Erik C} and Drost, {J. B.} and Lusher, {J. M.} and I. Warrier and A. Shapiro and Koerper, {M. A.} and D. Dimichele and J. Westman and Key, {N. S.} and Sommer, {S. S.}",
year = "1999",
doi = "10.1046/j.1365-2516.1999.00303.x",
language = "English (US)",
volume = "5",
pages = "101--105",
journal = "Haemophilia",
issn = "1351-8216",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Anaphylactic response to factor IX replacement therapy in haemophilia B patients

T2 - Complete gene deletions confer the highest risk

AU - Thorland, Erik C

AU - Drost, J. B.

AU - Lusher, J. M.

AU - Warrier, I.

AU - Shapiro, A.

AU - Koerper, M. A.

AU - Dimichele, D.

AU - Westman, J.

AU - Key, N. S.

AU - Sommer, S. S.

PY - 1999

Y1 - 1999

N2 - Haemophilia B is an X-linked recessive coagulopathy due to mutations in the factor IX gene. Occasionally, patients receiving factor IX replacement therapy develop inhibiting antibodies to the factor IX protein, and it has been recently documented that a subset of these patients have had anaphylactic responses to factor IX replacement therapy in association with the development of inhibiting antibodies. To determine the relationship between mutation type and the risk of anaphylaxis, eight unrelated patients from families in whom anaphylaxis had occurred were genotyped. The mutations were compared to those in 550 haemophilia B patients and to those in 276 patients with clinically severe disease. Individuals with complete gene deletions were found to be at greatest risk for anaphylaxis, with an estimated risk of 26% or greater. Anaphylaxis was less likely to occur in patients with protein truncation mutations or partial gene deletions and least likely to occur with missense mutations. Genotypes can help physicians and patients anticipate the likelihood of anaphylaxis, a potentially life-threatening complication of factor IX replacement therapy. The very high risk of anaphylaxis associated with a complete gene deletion suggests that the lack of expression of a partial protein product may predispose to anaphylaxis and/or that the absence of a closely linked, codeleted gene enhances the anaphylactic immune response.

AB - Haemophilia B is an X-linked recessive coagulopathy due to mutations in the factor IX gene. Occasionally, patients receiving factor IX replacement therapy develop inhibiting antibodies to the factor IX protein, and it has been recently documented that a subset of these patients have had anaphylactic responses to factor IX replacement therapy in association with the development of inhibiting antibodies. To determine the relationship between mutation type and the risk of anaphylaxis, eight unrelated patients from families in whom anaphylaxis had occurred were genotyped. The mutations were compared to those in 550 haemophilia B patients and to those in 276 patients with clinically severe disease. Individuals with complete gene deletions were found to be at greatest risk for anaphylaxis, with an estimated risk of 26% or greater. Anaphylaxis was less likely to occur in patients with protein truncation mutations or partial gene deletions and least likely to occur with missense mutations. Genotypes can help physicians and patients anticipate the likelihood of anaphylaxis, a potentially life-threatening complication of factor IX replacement therapy. The very high risk of anaphylaxis associated with a complete gene deletion suggests that the lack of expression of a partial protein product may predispose to anaphylaxis and/or that the absence of a closely linked, codeleted gene enhances the anaphylactic immune response.

KW - Allergic reaction

KW - Factor IX replacement

KW - Genotype-phenotype interactions

KW - Human factor IX mutations

KW - Nonsense mutations

KW - Total gene deletions

UR - http://www.scopus.com/inward/record.url?scp=6544277992&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=6544277992&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2516.1999.00303.x

DO - 10.1046/j.1365-2516.1999.00303.x

M3 - Article

C2 - 10215957

AN - SCOPUS:6544277992

VL - 5

SP - 101

EP - 105

JO - Haemophilia

JF - Haemophilia

SN - 1351-8216

IS - 2

ER -