Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation.
BACKGROUND
The cytokine interleukin-4 (IL-4) is secreted mainly by activated T lymphocytes and characterizes the T-helper 2 (Th2) sub-type. In transplantation Th2 cells are believed to induce graft tolerance. Previous studies revealed that patients with a relatively high frequency of IL-4 producing helper T lymphocytes (HTL) before heart transplantation (HTX) had no or less rejection episodes compared with patients with a low frequency of IL-4 producing HTL. Three single nucleotide polymorphisms (SNPs) have been identified in the promoter region of the IL-4 gene, which influence promoter strength. We investigated whether there was a correlation between SNP genotypes in the IL-4 promoter and heart failure, and rejection after HTX.


METHODS
Seventy HTX patients, 61 donors, and 36 controls were genotyped for the 3 SNPs by sequencing.


RESULTS
Of the SNPs at -285 and -81, only the C and A alleles, respectively, were found in this study. Both alleles were found for the -590 SNP. No relation between patient genotype of the SNP at -590 and heart failure and rejection was found. However, incidence of rejection was significantly lower in patients that received a donor heart with the T-positive genotype compared with patients that received a heart from a T-negative donor. Patients who had the T-negative genotype and received a heart from a T-positive donor, suffered significantly less from rejection than T-negative patients that received a T-negative donor heart. This was not significant in the T-positive patient group.


CONCLUSIONS
This indicates that IL-4 production within the donor heart and by cells from the donor is important for reducing incidence of episodes of rejection.
Bijlsma
Femke J
FJ
Department of Pathology University Medical Center Utrecht, Utrecht, The Netherlands. f.bijlsma@lab.azu.nl
vanKuik
Joyce
J
Tilanus
Marcel G J
MG
deJonge
Nicolaas
N
Rozemuller
Erik H
EH
van den Tweel
Jan G
JG
Gmelig-Meyling
Frits H J
FH
deWeger
Roel A
RA
D000483:Alleles; D002311:Cardiomyopathy, Dilated / Q000601:surgery; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics* / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D017202:Myocardial Ischemia / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D015847:Interleukin-4