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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, 111 Michigan Avenue, N.W., Washington, DC, United States; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States. Electronic address: ztataricalderone@sidra.org.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Tatari-Calderone
authors.affiliation: Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, United States; Center for Genetic Medicine Research, Children's National Health System, Washington, DC, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.affiliation: Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States; Division of Hematology and Oncology, Children's National Health System, Washington, DC, United States; Division of Laboratory Medicine, Children's National Medical Center, Washington, DC, United States.
authors.forename: Ross
authors.initials: R
authors.lastname: Fasano
authors.affiliation: Department of Biostatistics, Cato Research, Durham, NC, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Riggs
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, INSERM UMRS 1160, Monacord and ESH, Hôpital Saint-Louis, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fortier
authors.affiliation: Division of Pediatric Hematology/Oncology, University of Michigan Health System, Ann Arbor, MI, United States.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Campbell
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, INSERM UMRS 1160, Monacord and ESH, Hôpital Saint-Louis, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.affiliation: Section of Hematology/Oncology, University of Illinois Comprehensive Sickle Cell Center, Chicago, IL, United States.
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.affiliation: Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States; Division of Hematology and Oncology, Children's National Health System, Washington, DC, United States; Division of Laboratory Medicine, Children's National Medical Center, Washington, DC, United States.
authors.forename: Naomi L C
authors.initials: NLC
authors.lastname: Luban
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, 111 Michigan Avenue, N.W., Washington, DC, United States; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vukmanovic
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, INSERM UMRS 1160, Monacord and ESH, Hôpital Saint-Louis, Paris, France. Electronic address: Tamouza.ryad@gmail.com.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D002648:Child; D017707:Erythrocyte Transfusion; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008297:Male; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D007518:Isoantibodies; D007519:Isoantigens
keywords: Alloimmunization; HLA-DQB1; HLA-DRB1; Red Blood Cell transfusion; Sickle cell disease