Alloreactive Alleles for the IL-10 -1064 Polymorphism in the Donor Associate with Chronic GVHD, in a Chimerism Mediated Fashion, after HLA Identical Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract

Background: Polymorphisms in regulatory sequences of cytokine genes are known to influence their expression and, therefore, the intensity of the immune response. Some of such polymorphisms have been associated with the outcome of allogeneic stem cell transplantation (SCT).Objective: To evaluate the association between donor (D) and recipient (R) genotype for the IL-10 gene -1082 SNP (single nucleotide polymorphism) and -1064 STR (short tandem repeat) polymorphism with the dynamics of chimerism and the development of complications after SCT.Patients and methods: 24 HLA-matched conventional SCT. IL-10 genotypes were determined in an -1082 SNP allele-specific PCR (A vs G) including the -1064 STR in the product which is revealed by capillary electrophoresis. Results were analyzed using Fisher's exact test due to the reduced sample size.Results: The frequency of alloreactive genotypes (AA or A) for the SNP was 37,5% AA and 79,2% A in the D and 33,3 AA and 95,8% A in the R. No association was observed between the homozygous or heterozygous presence in the D or R of the alloreactive allele for the SNP genotype and the dynamics of chimerism or complications post-SCT. Alleles 4 to 10 for the STR genotype were found in contrast to previous reports (alleles 7–16). The frequency of alloreactive alleles (homozygous, +/+, or heterozygous, +), with greater number of dinucleotide repeats (alleles 8–10 in the present series) for the STR was 8,3% +/+ and 62,5% + in the D and 8,3% +/+ and 50% + in the R. The presence of alloreactive alleles (heterozygous) in the donor was significantly associated with the development of extense chronic GVHD (EcGVHD, Table 1). In patients transplanted from such donors, the incidence of mixed chimerism (MC) in peripheral blood during the first month post-SCT was lower although without statistical significance (Table 1). The higher alloreactivity of these donors favors the establishment of complete chimerism and therefore, increases the incidence of EcGVHD.Conclusions: The present study shows an association between the presence in the donor of alloreactive alleles for the IL-10 -1064 STR polymorphism and the development of EcGVHD, in a chimerism mediated fashion, after HLA- identical SCT. The analysis of a larger number of patients as well as further cytokines will eventually allow to confirm these observations and to establish this type of studies as a means for an improved management of transplanted patients. [Display omitted]