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

Transfus Med. 2022 Oct;32(5):394-401. doi: 10.1111/tme.12894. Epub 2022 Jul 1.

Abstract

Objective(s): 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.

Background: 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.

Methods/materials: 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.

Results: 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).

Conclusions: 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.

Keywords: HLA polymorphisms; HLA-antigens; alloimmunization; blood groups; cytokine polymorphisms; myelodysplastic syndromes.

MeSH terms

  • Anemia, Hemolytic, Autoimmune* / genetics
  • Brazil
  • Cytokines / genetics
  • Erythrocytes
  • HLA-DRB1 Chains* / genetics
  • Humans
  • Interleukin-17* / genetics
  • Interleukin-4* / genetics
  • Isoantibodies
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / therapy
  • Retrospective Studies

Substances

  • Cytokines
  • HLA-DRB1 Chains
  • IL17A protein, human
  • IL4 protein, human
  • Interleukin-17
  • Isoantibodies
  • Interleukin-4