Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease

Zohreh Tatari Calderone, Heather Gordish-Dressman, Ross Fasano, Michael Riggs, Catherine Fortier, Andrew D. Campbell, Dominique Charron, Victor R. Gordeuk, Naomi L.C. Luban, Stanislav Vukmanovic, Ryad Tamouza

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design: Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. Results: While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p = 0.02), -DQ3 (p = 0.02) and -DQ5 (p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p = 0.01) and HLA-DQ5/5 (p = 0.03) combinations constitute additional predictor of protective status. Conclusion: Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalHuman Immunology
Volume77
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Fingerprint

Sickle Cell Anemia
Logistic Models
Alleles
HLA-DQ Antigens
HLA-DRB1 Chains
Erythrocyte Transfusion
Erythrocytes
Isoantibodies
HLA-DR Antigens
Gene Frequency
Retrospective Studies
Regression Analysis
Databases
Antigens
Polymerase Chain Reaction
HLA-DQB1 antigen
Genes

Keywords

  • Alloimmunization
  • HLA-DQB1
  • HLA-DRB1
  • Red Blood Cell transfusion
  • Sickle cell disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease. / Tatari Calderone, Zohreh; Gordish-Dressman, Heather; Fasano, Ross; Riggs, Michael; Fortier, Catherine; Campbell, Andrew D.; Charron, Dominique; Gordeuk, Victor R.; Luban, Naomi L.C.; Vukmanovic, Stanislav; Tamouza, Ryad.

In: Human Immunology, Vol. 77, No. 1, 01.01.2016, p. 35-40.

Research output: Contribution to journalArticle

Tatari Calderone, Z, Gordish-Dressman, H, Fasano, R, Riggs, M, Fortier, C, Campbell, AD, Charron, D, Gordeuk, VR, Luban, NLC, Vukmanovic, S & Tamouza, R 2016, 'Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease', Human Immunology, vol. 77, no. 1, pp. 35-40. https://doi.org/10.1016/j.humimm.2015.10.010
Tatari Calderone, Zohreh ; Gordish-Dressman, Heather ; Fasano, Ross ; Riggs, Michael ; Fortier, Catherine ; Campbell, Andrew D. ; Charron, Dominique ; Gordeuk, Victor R. ; Luban, Naomi L.C. ; Vukmanovic, Stanislav ; Tamouza, Ryad. / Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease. In: Human Immunology. 2016 ; Vol. 77, No. 1. pp. 35-40.
@article{34f67dc43b404c86a566e11fafc25b00,
title = "Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease",
abstract = "Background: Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design: Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. Results: While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p = 0.02), -DQ3 (p = 0.02) and -DQ5 (p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p = 0.01) and HLA-DQ5/5 (p = 0.03) combinations constitute additional predictor of protective status. Conclusion: Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.",
keywords = "Alloimmunization, HLA-DQB1, HLA-DRB1, Red Blood Cell transfusion, Sickle cell disease",
author = "{Tatari Calderone}, Zohreh and Heather Gordish-Dressman and Ross Fasano and Michael Riggs and Catherine Fortier and Campbell, {Andrew D.} and Dominique Charron and Gordeuk, {Victor R.} and Luban, {Naomi L.C.} and Stanislav Vukmanovic and Ryad Tamouza",
year = "2016",
month = "1",
day = "1",
doi = "10.1016/j.humimm.2015.10.010",
language = "English",
volume = "77",
pages = "35--40",
journal = "Human Immunology",
issn = "0198-8859",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease

AU - Tatari Calderone, Zohreh

AU - Gordish-Dressman, Heather

AU - Fasano, Ross

AU - Riggs, Michael

AU - Fortier, Catherine

AU - Campbell, Andrew D.

AU - Charron, Dominique

AU - Gordeuk, Victor R.

AU - Luban, Naomi L.C.

AU - Vukmanovic, Stanislav

AU - Tamouza, Ryad

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design: Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. Results: While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p = 0.02), -DQ3 (p = 0.02) and -DQ5 (p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p = 0.01) and HLA-DQ5/5 (p = 0.03) combinations constitute additional predictor of protective status. Conclusion: Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.

AB - Background: Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design: Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. Results: While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p = 0.02), -DQ3 (p = 0.02) and -DQ5 (p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p = 0.01) and HLA-DQ5/5 (p = 0.03) combinations constitute additional predictor of protective status. Conclusion: Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.

KW - Alloimmunization

KW - HLA-DQB1

KW - HLA-DRB1

KW - Red Blood Cell transfusion

KW - Sickle cell disease

UR - http://www.scopus.com/inward/record.url?scp=84950986583&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84950986583&partnerID=8YFLogxK

U2 - 10.1016/j.humimm.2015.10.010

DO - 10.1016/j.humimm.2015.10.010

M3 - Article

C2 - 26476208

AN - SCOPUS:84950986583

VL - 77

SP - 35

EP - 40

JO - Human Immunology

JF - Human Immunology

SN - 0198-8859

IS - 1

ER -