Interleukin-10 Gene Polymorphisms in Allogeneic

Interleukin-10 Gene Polymorphisms in Allogeneic Bone Marrow Transplantation (BMT).

QAlbakri, DCook, EJBall, MKalaycio, BPohlman and BBolwell.Allogen Laboratories, The Cleveland Clinic Foundation, Cleveland OH, USA.

IL-10 is a potent inhibitor of T-cell responses against alloantigens.Low levels of IL-10 have been correlated with an increased incidence of both acute and chronic GVHD in allogeneic bone marrow transplantation.In this study we analyzed the genotype polymorphism of IL-10 promoter for 138 allogeneic bone marrow recipients, and in 104 cases, the corresponding donors to see whether IL-10 gene polymorphism correlates with survival rates and/or graft versus host disease (GVHD) severity in these recipients.The polymorphisms analyzed were those previously described to regulate gene expression at positions –1082 (G/A), -819 (C/T) and –592 (C/A).The method used for this study was a “reverse format” SSOP assay.

IL-10 polymorphisms and survival in allogeneic BMT:

IL-10 ALLELE	IL-10 PHENOTYPE	%Survival Post BMT
IL-10 ALLELE	IL-10 PHENOTYPE	Recipient	Donor
-1082 A/A	LOW	62%(32/52)	39%(9/23)
-1082 G/A	INTERMEDIATE	50%(27/54)	54 %(31/56)
-1082 G/G	HIGH	54%(17/32)	76%(19/25)
-819 T/T	LOW	55%(11/20)	62%(8/13)
-819 C/T	INTERMEDIATE	60%(34/57)	52%(24/46)
-819 CC	HIGH	51%(31/61)	57%(26/45)
-592 A/A	LOW	52%(11/20)	50%(7/14)
-592 C/A	INTERMEDIATE	64%(38/59)	67%(28/42)
-592 C/C	HIGH	47%(28/58)	48%(23/48)

In this preliminary study, only donor IL-10 (-1082) alleles significantly correlated with the survival of BMT recipients (p=0.032. Chi²).BMT recipients of IL-10 (-1082 A/A) donor showed reduced survival (39%) compared with those who received IL-10 (1082 G/G) donor(76%). These findings are consistent with the biological function of IL-10 as an anti-inflammatory and immunosuppressive agent. While more extensive studies are necessary for confirmation, these results suggest that it may be of benefit to select donors on the basis of cytokine polymorphisms to improve outcome.