Recipient Genotype for the IL-10 -1064 Promoter Gene STR Polymorphism Influences the Risk of Graft Failure/Rejection after HLA Matched Allogeneic Hematopoietic Stem Cell Transplant in a Chimerism Mediated Fashion.
Authors: Manzano Cintia , Balsalobre Pascual , Gomez-Pineda Alfonso , Diez-Martin Jose L. , Buño Ismael 
Published: April 2020

Background: Genetic polymorphisms within the regulatory sequence of cytokine genes influence their expression and, ultimately, the immune reactivity. Such polymorphisms are therefore associated with the outcome of stem cell transplantation (SCT) supporting the hypothesis of a genetic predisposition towards certain complications post-SCT.

Objective: To assess the association between donor (D) and recipient (R) genotypes for the IL-10 gene -1082 SNP (single nucleotide polymorphism) and -1064 STR (short tandem repeat) polymorphisms with the dynamics of chimerism and the development of complications after SCT.

Patients and methods: The study included 39 conventional SCT from HLA-matched related donors. IL-10 genotypes were determined in an -1082 SNP allele-specific PCR (A vs G) including the -1064 (CA)n 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 35,9% AA and 87,2% A in the D and 25,6% AA and 89,7% A in the R. No association was observed between the 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 (17 CA repeats) to 12 (25 CA repeats) for the STR genotype were found in the present series. The frequency (homozygous, +/+, or heterozygous, +) of the low IL-10 producer allele 7 (high alloreactivity allele) was 5,1% +/+ and 25,6% + in the D and 7,7% +/+ and 33,3% + in the R. The presence of allele 7 in the recipient was significantly associated with the development of graft failure/rejection (p=0,012; Table ). In these patients, the incidence of mixed chimerism (MC) in the CD3+ fraction (T lymphocytes) during the first month post-SCT was significantly higher (p=0,043; Table 1).

Conclusions: The presence of the low producer allele 7 for the IL-10 -1064 STR polymorphism in the recipient would associate with a higher immune alloreactivity against donor cells. This would favour the establishment of mixed chimerism increasing the risk of graft failure/rejection. Therefore, our results suggest that recipient IL-10 -1064 STR polymorphism genotypes may influence SCT outcome in a chimerism mediated fashion. 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.

Table 1. Influence of the presence in the recipients of allele 7 for the IL-10 -1064 STR polymorphism on chimerism and complications post-STC. IL-10 -1064 allele 7 MC day+30 in T cells (CD3+) aGVHD II-IV cGVHD Graft failure/rejection Relapse Exitus Present 6/6 (100%) 6/12 (45,5%) 6/10 (60%) 5/13 (38,5%) 3/12 (25%) 6/13 (46,2%) Not present 6/13 (50%) 13/26 (50%) 16/18 (88,9%%) 1/26 (4%) 7/25 (28%) 12/26 (46,2%) p (Fisher’s Test) 0,043 NS NS 0,012 NS NS