Investigation of MHC gamma block C4A and C4B polymorphisms in unrelated hematopoietic stem cell transplantation
AUTOR(ES)
Getz, Joselito; Goldenstein, Monica; Bonfim, Carmem; Funke, Vaneuza Moreira; Colturato, Vergílio; Hamerschlak, Nelson; Torres, Margareth; Sayer, David; Boldt, Angelica; Pasquini, Ricardo; Pereira, Noemi Farah
FONTE
Hematol., Transfus. Cell Ther.
DATA DE PUBLICAÇÃO
2020-09
RESUMO
ABSTRACT Background: Immunological life-threatening complications frequently occur in post-hematopoietic stem cell transplantation (HSCT), despite matching recipient and donor (R/D) pairs for classical human leukocyte antigens (HLA). Studies have shown that R/D non-HLA disparities within the major histocompatibility complex (MHC) are associated with adverse effects post-HSCT. Methods: We investigated the impact of mismatches of single-nucleotide polymorphisms (SNPs) in C4A/C4B genes, for showing the highest diversity in the MHC gamma block, on 238 patients who underwent HLA 10/10 unrelated donor (URD) HSCT. The endpoints were acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD) and mortality. One hundred and twenty-nine R/D pairs had 23 C4-SNPs typed by PCR-SSP (Gamma-Type™v.1.0), and 109 R/D pairs had these 23 SNPs identified by next-generation sequencing (NGS) using the Illumina platform. Results: The percentage of patients who received HSC from HLA 10/10 donors with 1-7 mismatches was 42.9%. The R/D pairs were considered C4 mismatched when bearing at least one disparity. These mismatches were not found to be risk factors for aGVHD, cGVHD or mortality after unrelated HSCT when SNPs were analyzed together (matched or mm ≥ 1), independently or according to the percentage of incompatibilities (full match for 23 SNPs; 1-3 mm and >3 mm). An exception was the association between 1-3 mismatches at the composite of SNPs C13193/T14952/T19588 with the development of aGVHD (P = 0.012) and with grades III-IV of this disease (P = 0.004). Conclusion: Our data are not consistent with the hypothesis that disparities in C4A/C4B SNPs increase the risks of post-HSCT adverse effects for the endpoints investigated in this study.
Documentos Relacionados
- Unrelated hematopoietic stem cell transplantation in the pediatric population: single institution experience
- Impact of C4 , C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus
- Genetic Sophistication of Human Complement Components C4A and C4B and RP-C4-CYP21-TNX (RCCX) Modules in the Major Histocompatibility Complex
- Determining the One, Two, Three, or Four Long and Short Loci of Human Complement C4 in a Major Histocompatibility Complex Haplotype Encoding C4A or C4B Proteins
- Neutropenic diets in hematopoietic stem cell transplantation