Polimorfismo HLA e MICA em candidatos ao transplante renal da região Norte/Noroeste do Estado do Paraná

Abstract

The HLA (Human leukocyte antigen) system is an important marker of graft survival.While the importance of HLA-A, -B, and -DR in solid-organ transplantation has been known for many years, the role of HLA-C, HLA-DQ and MICA (major histocompatibility complex MHC class I chain-related gene A) in the transplantation has recently been documented. In this study, we evaluated the allelic and haplotype frequencies of MICA; HLA-A, -B, -C, - DRB1, -DQA1 and -DQB1 in 346 patients, of different ethnicities, with chronic kidney disease (CKD), renal transplant candidates from Northern/Northwestern of Parana State, Southern Brazil. HLA and MICA typing were performed using the polymerase chain reactionsequence specific primer method (PCR-SSO), combined with the Luminex technology. The allelic frequencies of MICA and the linkage disequilibrium with HLA-B alleles were studied in the same samples. The 346 participants were classified according to ethnic group (189 caucasians, 98 mestizos, 50 blacks and 9 orientals). A total of 19 MICA, 20 HLA-A, 29 HLAB and 14 HLA-C, 13 HLA-DRB1, 6 HLA-DQA and 5 HLA-DQB1 allele groups were identified. The most frequent allele groups were MICA*008, HLA-A*02, B*35, C*07, DRB1*04, DQA1*01 and DQB1*03. Significant differences (p<0.05) were observed in MICA*009, MICA*010, HLA-A*24, A*68, B*52, DRB1*09, C*03, C*07 and DQA1*03 allele group frequencies between ethnic groups. The most common extended haplotype in the total samples was HLA-A*01-C*07-B*08-MICA*008-DRB1*03-DQA1*05-DQB1*02 (2.4%). The most common haplotypes were MICA*009-B*51 (7.8%), MICA*004-B*44 (6.1%) and MICA*002-B*35 (5.6%). As expected from the proximity of the MICA and HLA-B loci, most haplotypes showed strong LD. Renal patients and healthy subjects in the same region of Brazil showed statistically significant differences in their MICA polymorphisms. The MICA*027 allele group was more frequent in renal patients (Pc=0.018; OR: 3.4; CI 95%: 1.5- 7.7), while the MICA*019 allele group was more frequent in healthy subjects (Pc<0.01; OR: 0.0; CI 95%: 0.0-0.5). The MICA; HLA-A ,-B, -C, -DRB1, -DQA1, -DQB1 alleles and haplotypes frequencies were studied in 346 renal-transplant candidates. An ethnic contribution was shown in the analyzed samples, with evidence that the Brazilian population is composed of a mixture of ethnicities, and that the HLA and MICA contribution can be determined by the predominant ethnicity of each region, since the alleles of European origin presented in greater number than the others. However, a number of other allelic groups have been found, which may result from the contribution of alleles from different Amerindian or European, African and Asian opopulations that colonized the region. Knowledge of HLA and MICA diversity in patients with CKD, potential candidates for transplantation in a region and its comparison with healthy individuals may favor a better understanding of the association between MHC antigens and the development of renal disease. Finally, our data could be useful as a preliminary clinical reference for better understanding of the mechanisms involved in the allograft rejection associated with HLA and MICA polymorphisms in the Brazilian population.