The cornerstone of the management of Beta Thalassemia Major (B-TM) is lifelong Red Blood Cells (RBC) transfusion. This is associated with the development of RBCs alloantibodies. Human Leukocyte Antigen (HLA) is considered a risk factor for a number of autoimmune disorders. We hypothesized that HLA impacts the rate of alloantibody formation in patients with B-TM.
To assess the impact of HLA alleles on the risk of RBC alloimmunization in patients with B-TM.
This is a retrospective cohort study of patients with B-TM managed at Sultan Qaboos University Hospital (SQUH) between January 1996 till December 2016. All adult and paediatric patients with B-TM with available HLA typing results were included. Patients with missing data were excluded. Chi-squared test was used to assess the impact of HLA alleles on alloimmunization and the effect size was estimated using odd ratio (OR). HLA testing was performed using polymerase chain reaction – specific sequence of oligonucleotides (PCR-SSO). Gel card technique (BIORAD ID-System; DiaClon, Bio-Rad, DiaMed GmbH, Switzerland) was used to screen for the RBC alloantibodies.
One hundred and sixty-five patients fulfilled the inclusion criteria without missing information. The median age of all patients was 14 years. Females constituted 48% of the sample and 45% of patients were O RhD positive. The median RBC transfusion was 17 times per year. Patients were first detected to have RBC alloantibody at a median age of 16 years. The commonest RBC alloantibodies found in these patients were anti-K (50%) and anti-E (58%). The commonest HLA allele in loci A, B, C, DQ and DRB1 were HLA-A∗02 (21%), HLA-B∗51 (14%), HLA-C∗7 (18%), HLA-DQ∗05 (47%) and HLA-DRB1∗16 (32%) respectively. HLA-DRB1∗15 and HLA-DQ∗6 were associated with a higher risk of RBC alloantibody formation (HLA-DRB1∗15: OR 3.57, P = 0.047; HLA-DQ∗06: OR 4.37, P = 0.025). None of the remaining common alleles (>5%) in Omani population were associated with the risk of alloantibody formation (p values >0.05).
HLA-DRB1∗15 and HLA-DQ∗06 increases the risk of RBC alloantibody formation in patients with B-TM. We recommend extended RBC phenotyping and extended antigen matched blood transfusion in patients carrying these two alleles. These findings will need to be confirmed in a larger multicenter study.