HLA-DRB1 and cytokine polymorphisms in Brazilian patients with myelodysplastic syndromes and its association with red blood cell alloimmunization.

Abstract

This study aimed investigate association of HLA-DRB1 and cytokine polymorphisms with red blood cell(RBC) alloimmunization in Brazilian Myelodysplastic syndrome(MDS) patients with prior exposure to RBC transfusion. MDS patients are at risk RBC alloimmunization due to chronic RBC transfusion. However, differences in immune response of MDS transfused patients are not completely known. A retrospective cohort of 87 polytransfused patients with MDS including 28 alloimmunized (PA) and 59 non-alloimmunized (PNA) was evaluated in three Brazilian reference hospitals. HLA-DRB1genotype was performed by polymerase chain reaction (PCR)-SSOP (Luminex platform) and cytokine polymorphisms analysed by PCR and TaqMan assays. While HLA-DRB1 allele frequencies did not differ between groups, IL17A 197G > A SNP and IL4 polymorphisms showed significant correlation with RBC alloimmunization. IL17A 197A allele A and AA genotype were significantly more frequent in PA than PNA(A, 46.4% versus 27.1%, p= 0.012; OR=2.3; 95%CI=1.1-4.9; AA, 25% versus 6.8%, p= 0.041; OR=6.2; 95%CI 1.3-30.8). Moreover, significant association of alloimmunization to Rh antigens with IL17A 197A allele and AA genotype was also identified in PA group(A, 45% versus 27.1%, p= 0.036; OR=2.5; 95% CI 1.1-5.7; AA, 30% versus 6.8%, p= 0.042; OR=7.9; 95%CI 1.5-42.3). Genotype A1A2 of IL4 intron 3 was overrepresented in PA(50% versus 16.9%, p= 0.009; OR=4.97; 95%CI 1.6-15.5). Similarly, IL4-590 CT genotype was overrepresented in PA(53.6% versus 28.8%, p= 0.049; OR=3.3; 95%CI 1.2-9.3). This study showed no association regarding HLA-DRB1 alleles for RBC alloimmunization risk or protection, however the IL17A 197G>A, IL4 intron 3 and IL4 590C>T SNP was significantly associated to RBC alloimmunization risk in this cohort of Brazilian MDS patients.