title: Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms.
abstract: The reason for the difference in susceptibility to red blood cell (RBC) alloimmunization among patients with sickle cell disease (SCD) is not clearly understood and is probably the result of multiple factors. Our hypothesis is that genetic polymorphisms are associated with RBC alloimmunization.
  
  
  
  We investigated the possible association of susceptibility to RBC alloimmunization with polymorphisms of HLA and cytokines genes in 161 SCD patients prior exposed to RBC transfusion. Cytokine gene polymorphisms were analyzed by polymerase chain reaction (PCR) and TaqMan assays. HLA Class I genotyping was performed using PCR-specific sequence of oligonucleotides. Polymorphism frequencies were compared using the Fisher's exact test.
  
  
  
  Our results revealed increased percentage of the A allele and the GA genotype of the TNFA -308G/A cytokine among alloimmunized patients when compared to nonalloimmunized patients (A allele, 16.4% vs. 6.8%, p = 0.004; GA genotype, 32.8% vs. 11.7%, p = 0.0021). In addition, the IL1B -511T allele and the IL1B -511TT and CT genotype frequencies were overrepresented among alloimmunized patients (T allele, 53.0% vs. 37.5%, p = 0.0085; CT + TT genotypes, 81.82% vs. 60.87%, p = 0.0071). In relation to HLA Class I, we found a higher frequency of HLA-DRB1*15 among patients alloimmunized to Rh antigens when compared to nonalloimmunized patients (15.63% vs. 6.98%, p = 0.044).
  
  
  
  Brazilian SCD patients with the TNFA, IL1B, and HLA-DRB1 gene polymorphisms were at increased risk of becoming alloimmunized by RBC transfusions. These findings may contribute to the development of future therapeutic strategies for patients with SCD with higher susceptibility of alloimmunization.
authors.affiliation: Hematology and Hemotherapy Center, State University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Emilia Ângela
authors.initials: EÂ
authors.lastname: Sippert
authors.affiliation: Basic Health Sciences Department, State University of Maringa, Maringá, Paraná, Brazil.
authors.forename: Jeane Eliete Laguila
authors.initials: JE
authors.lastname: Visentainer
authors.affiliation: Basic Health Sciences Department, State University of Maringa, Maringá, Paraná, Brazil.
authors.forename: Hugo Vicentin
authors.initials: HV
authors.lastname: Alves
authors.affiliation: Basic Health Sciences Department, State University of Maringa, Maringá, Paraná, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Rodrigues
authors.affiliation: Hematology and Hemotherapy Center, State University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Simone Cristina Olenscki
authors.initials: SC
authors.lastname: Gilli
authors.affiliation: Hematology and Hemotherapy Center, State University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Addas-Carvalho
authors.affiliation: Hematology and Hemotherapy Center, State University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Sara Teresinha Ollala
authors.initials: ST
authors.lastname: Saad
authors.affiliation: Hematology and Hemotherapy Center, State University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
authors.affiliation: Hematology and Hemotherapy Center, State University of Campinas, UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Lilian
authors.initials: L
authors.lastname: Castilho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012203:Rh Isoimmunization / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; C508585:IL1B protein, human; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha