Allele and haplotype frequencies of HLA‐A, B, C, DRB1 and DQB1 genes in polytransfused patients in ethnically diverse populations from Brazil

Abstract

The red blood transfusion is a practice often used in patients with haematological and oncological diseases. However, the investigation of human leucocyte antigen (HLA) system frequency in these individuals is of great importance because multiple transfusions may lead to HLA alloimmunization. Brazil is a country that was colonized by many other ethnicities, leading to a mixed ethnicity and regionalized population. In view of the importance of HLA typing in these patients, the aim of this study was to investigate the allele and haplotype frequencies from polytransfused patients from three different regions from Brazil. HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genotyping of 366 patients was performed by PCR-SSO, based on the Luminex technology (One Lambda(®) ), and the anti-HLA class I and class II antibodies were analysed using LabScreen Single Antigen Antibody Detection (One Lambda, Inc.). Allele and haplotype frequencies of polytransfused patients of three regions from Brazil were obtained using the Arlequin program. The most frequent allele frequencies observed were HLA-A*02, A*03, B*15, B*35, B*51, C*07, C*04, C*03, DRB1*13, DRB1*11, DRB1*07, DRB1*03, DRB1*01, DQB1*03, DQB1*02, DQB1*06 and DQB1*05. There were differences between the groups for allele variants HLA-B*57 (between Group 1 and Group 2) and HLA-C*12 (between Group 1 and Group 3). The most frequent haplotypes found in the sample were HLA-A*01B*08DRB1*03, DRBI*07DQB1*02, DRB1*01DQB1*05, DRB1*13DQB1*06 and A*02B*35. HLA class I and II antibodies were detected in 77.9% and 63.9% patients, respectively, while the both alloantibodies were detected in 62 (50.9%) patients. In conclusion, the HLA typing for polytransfused patients in each region has a great importance, as seen in this study; individuals from different regions from Brazil have HLA distribution not completely homogeneous.

A genomic study on distribution of human leukocyte antigen ( HLA ) -A and HLA-B alleles in Lak population of Iran

“…In a Brazilian population the most frequent alleles were A*02, A*03, B*15, B*35, B*51 [44]. Alleles B*35 and B*51 high frequency was like Lak population, whereas B*15 is low frequent in Lak population.…”

HLA diversity in Brazil

“…Although differences in allelic frequency were observed between the three groups, the most common haplotype was HLA‐A*01~B*08~DRB1*03 . In this sample, HLA class I and II antibodies were detected in 77.9% and 63.9% of patients, respectively, while both alloantibodies were detected in 50.9% of patients . In a group of 172 patients with sickle cell anemia (44 alloimmunized and 128 non‐alloimmunized), all treated in the state of São Paulo and classified as Black or Admixed , the number of transfusions received directly influenced the incidence of alloimmunization.…”

“…Interestingly, population groups composed by polytransfused patients are located distant from the other urban populations in the graph (Figure B‐D). Non‐excluding alternative hypotheses for such differences in allele frequency are a relatively small sample size for this group, an overrepresentation of alleles associated with this condition, or a specific genetic ancestry profile, as these individuals identified as Admixed or Black .…”

“…Rodrigues et al characterized HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 diversity in three different groups of multiple transfused patients: Admixed from Paraná, Admixed from São Paulo and “Afro‐Brazilians” ( Black ) from the Northeast region of Brazil. Although differences in allelic frequency were observed between the three groups, the most common haplotype was HLA‐A*01~B*08~DRB1*03 .…”

“…In this sample, HLA class I and II antibodies were detected in 77.9% and 63.9% of patients, respectively, while both alloantibodies were detected in 50.9% of patients. 62 In a group of 172 patients with sickle cell anemia (44 alloimmunized and 128 non-alloimmunized), all treated in the state of São Paulo and classified as Black or Admixed, the number of transfusions received directly influenced the incidence of alloimmunization. In this study, the HLA-C*06 and HLA-DQB1*03 alleles had a significantly higher frequency in alloimmunized patients, suggesting that carriers of these alleles are more susceptible to alloimmunization 54 (Table 2).…”