Identification of genetic biomarkers for alloimmunization in sickle cell disease

Sanne M. Meinderts, Jorn J. Gerritsma, Joep W. R. Sins, Martin de Boer, Karin van Leeuwen, Bart J. Biemond, Anita W. Rijneveld, Jean-Louis H. Kerkhoffs, Anoosha Habibi, Robin van Bruggen, Taco W. Kuijpers, Ellen van der Schoot, France Pirenne, Karin Fijnvandraat, Michael W. Tanck, Timo K. van den Berg

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30% of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll-like receptor pathway or in genes previously associated with antibody-mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case-control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.
Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusPublished - 2019

Cite this

Meinderts, Sanne M. ; Gerritsma, Jorn J. ; Sins, Joep W. R. ; de Boer, Martin ; van Leeuwen, Karin ; Biemond, Bart J. ; Rijneveld, Anita W. ; Kerkhoffs, Jean-Louis H. ; Habibi, Anoosha ; van Bruggen, Robin ; Kuijpers, Taco W. ; van der Schoot, Ellen ; Pirenne, France ; Fijnvandraat, Karin ; Tanck, Michael W. ; van den Berg, Timo K. / Identification of genetic biomarkers for alloimmunization in sickle cell disease. In: British Journal of Haematology. 2019.
@article{35f248dcc6cc404b9a5db2b2b56e3d13,
title = "Identification of genetic biomarkers for alloimmunization in sickle cell disease",
abstract = "Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30{\%} of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll-like receptor pathway or in genes previously associated with antibody-mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case-control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.",
author = "Meinderts, {Sanne M.} and Gerritsma, {Jorn J.} and Sins, {Joep W. R.} and {de Boer}, Martin and {van Leeuwen}, Karin and Biemond, {Bart J.} and Rijneveld, {Anita W.} and Kerkhoffs, {Jean-Louis H.} and Anoosha Habibi and {van Bruggen}, Robin and Kuijpers, {Taco W.} and {van der Schoot}, Ellen and France Pirenne and Karin Fijnvandraat and Tanck, {Michael W.} and {van den Berg}, {Timo K.}",
year = "2019",
doi = "10.1111/bjh.15998",
language = "English",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",

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Meinderts, SM, Gerritsma, JJ, Sins, JWR, de Boer, M, van Leeuwen, K, Biemond, BJ, Rijneveld, AW, Kerkhoffs, J-LH, Habibi, A, van Bruggen, R, Kuijpers, TW, van der Schoot, E, Pirenne, F, Fijnvandraat, K, Tanck, MW & van den Berg, TK 2019, 'Identification of genetic biomarkers for alloimmunization in sickle cell disease' British Journal of Haematology. https://doi.org/10.1111/bjh.15998

Identification of genetic biomarkers for alloimmunization in sickle cell disease. / Meinderts, Sanne M.; Gerritsma, Jorn J.; Sins, Joep W. R.; de Boer, Martin; van Leeuwen, Karin; Biemond, Bart J.; Rijneveld, Anita W.; Kerkhoffs, Jean-Louis H.; Habibi, Anoosha; van Bruggen, Robin; Kuijpers, Taco W.; van der Schoot, Ellen; Pirenne, France; Fijnvandraat, Karin; Tanck, Michael W.; van den Berg, Timo K.

In: British Journal of Haematology, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Identification of genetic biomarkers for alloimmunization in sickle cell disease

AU - Meinderts, Sanne M.

AU - Gerritsma, Jorn J.

AU - Sins, Joep W. R.

AU - de Boer, Martin

AU - van Leeuwen, Karin

AU - Biemond, Bart J.

AU - Rijneveld, Anita W.

AU - Kerkhoffs, Jean-Louis H.

AU - Habibi, Anoosha

AU - van Bruggen, Robin

AU - Kuijpers, Taco W.

AU - van der Schoot, Ellen

AU - Pirenne, France

AU - Fijnvandraat, Karin

AU - Tanck, Michael W.

AU - van den Berg, Timo K.

PY - 2019

Y1 - 2019

N2 - Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30% of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll-like receptor pathway or in genes previously associated with antibody-mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case-control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.

AB - Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30% of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll-like receptor pathway or in genes previously associated with antibody-mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case-control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31168801

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