Interleukin-10 gene polymorphism in bone marrow transplant recipients.
ABSTRACT Graft-versus-host disease is the main complication after hematopoietic stem cell transplant, occurring even after donor and recipient human leukocyte antigen matching, apparently because of donor/recipient minor histocompatibility antigen mismatches and cytokine polymorphisms. Interleukin-10 suppresses several activities of the immune response by inhibiting T helper 1 and T helper 2 cells. These properties suggest that interleukin-10 could act as a suppressive mediator and prevent graft-versus-host disease. This study evaluates the association between the interleukin-10 promoter gene polymorphism and transplant outcomes among 18 recipients of cytokine-mobilized peripheral blood stem cells from human leukocyte antigen-matched sibling donors.
We analyzed 3 single nucleotide polymorphisms in the proximal region of the interleukin-10 promoter gene (-1082/-819/-592) by the amplification refractory mutation system and polymerase chain reaction-restriction fragment length polymorphism methods. Eighteen donors and their recipients who had undergone an allogeneic peripheral blood stem cell transplant at the Bone Marrow Transplant Center in Nemazi Hospital (Shiraz, Southern Iran) between September 2005 and September 2006 were enrolled.
The GCC haplotype (1082G/819C/592C) was predominant in both the donor and the recipient, but no significant correlations were present between the GCC haplotype in either the donor or the recipient and the risk of acute graft-versus-host disease (P = .56).
The interleukin-10 promoter gene polymorphism was found not to be associated with acute graft-versus-host disease in patients after an allogeneic peripheral blood stem cell transplant from human leukocyte antigen-matched sibling donors. Additional studies with larger samples are necessary to further define the influence of interleukin-10 on the immune response after bone marrow transplant.
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ABSTRACT: The bulk of evidences indicates that variations in the coding for cytokines or the regulation of their expression may play a role in acute graft-versus-host disease (aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). It is unclear whether IL-10 promoter polymorphism is associated with the occurrence of aGvHD in allogeneic HSCT. A systematic search was performed in PubMed and Embase databases and 10 studies were identified for inclusion. Data were extracted and pooled ORs together with 95 % CIs were calculated. The pooled result indicated that -592A allele in recipient was significantly associated with reduced risk of moderate aGvHD in HSCT [OR = 0.41 (0.21, 0.79), P = 0.008, I (2) = 25 %]. The same pattern was also obtained from the -819T allele in recipient [OR = 0.38 (0.18, 0.79), P = 0.01, I (2) = 41 %]. Furthermore, we found a significant positive correlation between the -592AA homozygote and lower risk of severe aGvHD in HSCT [OR = 0.54 (0.34, 0.86), P = 0.01, I (2) = 29 %]. The similar result was gained from the -1082A allele in recipient and decreased risk of severe aGvHD [OR = 0.71 (0.52, 0.98), P = 0.04, I (2) = 19 %]. However, there was no significant association between -592A, -819T, or -1082A allele in donor and risk of aGvHD. This meta-analysis suggests that the IL-10 A allele or AA homozygote at -592, T allele at -819 and the A allele at -1082 are associated with reduced risk of aGvHD in allogeneic HSCT.International journal of hematology 05/2013; · 1.17 Impact Factor
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ABSTRACT: Four hundred and ninety-five patients (390 and 105 grafted from unrelated and sibling (SIB) donors, respectively) and their donors were analyzed for the impact of interleukin-10 (IL-10) promoter genotype [rs18000896 (-1082 G/A), rs18000871 (-819 C/T) and rs18000872 (-592 C/A)] on the outcome of hematopoietic stem cell transplantation (HSCT). Patients having ACC haplotype were at a lower risk of acute graft versus host disease (aGvHD, grade > I) if transplanted from human leukocyte antigen (HLA) well-matched (10/10) unrelated donors (20/135 vs 39/117, P < 0.001, Pcorr = 0.002), which was not seen if patients were transplanted from either sibling (SIB) or poorly matched (<10/10) unrelated donors (MUD). In addition, GCC haplotype positive recipients of unrelated donor transplants tended to be more susceptible to aGvHD (68/199 vs 39/169, P = 0.019, Pcorr = 0.057). Multivariate logistic regression analysis in the MUD transplanted group showed that donor-recipient human leukocyte antigen (HLA) mismatch [odds ratio (OR) = 3.937, P = 0.001] and a lack of ACC haplotype in recipients (OR = 0.417, P = 0.013) played a significant role as independent risk factors of aGvHD grade > I. ACC carriers had higher proportions of FoxP3+ lymphocytes gated in CD4+ lymphocytes as compared with patients with other IL-10 haplotypes. It was seen at the time of hematological recovery (mean ± SEM: 3.80 ± 0.91% vs 2.06 ± 0.98%, P = 0.012) and 2 weeks later (5.32 ± 0.87% vs 2.50 ± 0.83%, P = 0.013); -592 C/A polymorphism was separately analyzed and it was found that AA homozygotes tended to have a higher incidence of aGvHD (8/15 vs 116/456, P = 0.034) and low proportions of FoxP3 CD4+ lymphocytes in blood (0.43 ± 0.22% vs 4.32 ± 0.71%, P = 0.051) measured 2 weeks after hematological recovery. Functional IL-10 polymorphism associated features influenced the risk of aGvHD with a positive effect of ACC on the pool of Treg in blood.Tissue Antigens 12/2013; 82(6):387-96. · 2.35 Impact Factor
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ABSTRACT: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.São Paulo medical journal = Revista paulista de medicina 01/2012; 130(4):219-24. · 0.75 Impact Factor