Plaza Diana M, Fernández Darío, Builes Miguel, Villegas Alberto, García Luis F
Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
J Heart Lung Transplant. 2003 Aug;22(8):851-6. doi: 10.1016/s1053-2498(02)00812-4.
Cytokines are important modulators of post-transplant, allogeneic immune responses. In heart transplantation, endomyocardial biopsies allow monitoring of histologic and immunologic events that occur inside the graft; their correlation with risk factors condition graft outcome. Recent reports indicate that various cytokine gene allelic polymorphisms control the number of cytokines produced and may be associated with graft outcome.
We studied 71 heart transplant recipients between December 1985 and December 2000. We used sequence-specific primers (SSP) polymerase chain reaction to study interleukin-10 (IL-10) polymorphisms at -1082 (G/A), -819 (C/T), and -592 (C/A); tumor necrosis factor alpha (TNF-alpha) at -308 (G/A) and -238 (G/A); transforming growth factor beta (TGF-beta) variants at codon 10 (C/T) and codon 25 (G/C); and interferon-gamma (IFN-gamma) polymorphisms at +874 (T/A). We determined the association of allele, genotype, and haplotype frequencies with the presence of histologically proven rejection episodes (according to International Society for Heart and Lung Transplantation criteria) and the presence of Quilty lesions in endomyocardial biopsy specimens.
We found no association between the polymorphisms studied and the frequency and severity of acute and chronic rejection episodes. However, the gene frequency of allele A at IL-10 -1082, associated with decreased IL-10 production, was increased in patients with Quilty lesions (p = 0.0027, odds ratio = 2.98). Similarly, we found more AA homozygous individuals, compared with AG heterozygous and GG homozygous individuals (p = 0.0017), among patients with Quilty effect. The ATA and ACC IL-10 haplotypes also were associated with Quilty effect (p = 0.0051).
These results suggest that genetically controlled decreased IL-10 production predisposes to the development of Quilty lesions. The decreased negative regulatory effect of IL-10 on T cells and macrophages may result in enhanced graft infiltration.
细胞因子是移植后同种异体免疫反应的重要调节因子。在心脏移植中，心内膜活检可监测移植物内发生的组织学和免疫学事件；它们与危险因素的相关性决定了移植物的结局。最近的报告表明，各种细胞因子基因等位基因多态性控制着产生的细胞因子数量，并可能与移植物结局相关。
我们研究了1985年12月至2000年12月期间的71名心脏移植受者。我们使用序列特异性引物（SSP）聚合酶链反应来研究白细胞介素-10（IL-10）在-1082（G/A）、-819（C/T）和-592（C/A）位点的多态性；肿瘤坏死因子α（TNF-α）在-308（G/A）和-238（G/A）位点的多态性；转化生长因子β（TGF-β）在密码子10（C/T）和密码子25（G/C）位点的变体；以及干扰素-γ（IFN-γ）在+874（T/A）位点的多态性。我们确定了等位基因、基因型和单倍型频率与组织学证实的排斥反应发作（根据国际心肺移植学会标准）的存在以及心内膜活检标本中奎尔蒂病变的存在之间的关联。
我们发现所研究的多态性与急性和慢性排斥反应发作的频率和严重程度之间没有关联。然而，IL-10 -1082位点的A等位基因的基因频率与IL-10产生减少相关，在有奎尔蒂病变的患者中增加（p = 0.0027，优势比 = 2.98）。同样，在有奎尔蒂效应的患者中，与AG杂合子和GG纯合子个体相比，我们发现更多的AA纯合子个体（p = 0.0017）。ATA和ACC IL-10单倍型也与奎尔蒂效应相关（p = 0.0051）。
这些结果表明，基因控制的IL-10产生减少易导致奎尔蒂病变的发生。IL-10对T细胞和巨噬细胞的负调节作用降低可能导致移植物浸润增强。
