Uboldi de Capei Mariafederica, Dametto Ennia, Fasano Maria E, Messina Maria, Pratico' Loredana, Rendine Sabina, Segoloni Giuseppe, Curtoni Emilio S
Genetics Institute, Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Piemonte, Italy.
Transplantation. 2004 Feb 27;77(4):548-52. doi: 10.1097/01.tp.0000114291.01231.dd.
In part, the long-term survival of kidney transplants depends on the efforts to perform grafts with good human leukocyte antigen (HLA) compatibility, but there are other mechanisms that must induce some sort of tolerance and impair the anti-graft immune reaction. Because cytokines are one of the main components of immune response, we evaluated single nucleotide polymorphisms (SNPs) of several cytokine genes that may influence the production of a given cytokine and therefore the features of immune reactions.
A total of 416 first cadaveric kidney transplants were monitored for HLA matching. After 10 years, the graft was still functional in 171 of 416 patients; 102 of 171 patients were also typed for cytokine polymorphisms.
The mismatch distributions in patients who underwent transplantation were not statistically different from the entire group of patients who underwent transplantation during the same time period. Moreover, it seems that almost all of the HLA class I incompatible long-term survivors are homozygous for GG at the -1082 interleukin (IL)-10 or CC at the -33IL4.
We observed that a match for class I and class II HLA antigens apparently does not favor the long-term survival of transplanted kidneys. In fact, matched grafts are lost before 10 years in the same proportion as the mismatched grafts. We also demonstrated (1) that patients who are homozygous for GG at the SNP -1082IL10 (high IL-10 producers) and HLA class I mismatched (but matched for class II) are protected from chronic rejection, and (2) that patients who are homozygous for CC at the SNP -33IL4 (low IL-4 producers) and HLA class I mismatched (regardless of matching for class II) are protected from chronic rejection.
肾移植的长期存活部分取决于进行具有良好人类白细胞抗原（HLA）相容性移植的努力，但还有其他机制必须诱导某种耐受性并削弱抗移植免疫反应。由于细胞因子是免疫反应的主要组成部分之一，我们评估了几个细胞因子基因的单核苷酸多态性（SNP），这些基因可能影响特定细胞因子的产生，从而影响免疫反应的特征。
对总共416例首次尸体肾移植进行HLA配型监测。10年后，416例患者中有171例的移植肾仍具有功能；对这171例患者中的102例也进行了细胞因子多态性分型。
接受移植患者的错配分布与同期接受移植的整个患者组相比无统计学差异。此外，似乎几乎所有I类HLA不相容的长期存活者在白细胞介素（IL）-10的-1082位点为GG纯合子或在IL-4的-33位点为CC纯合子。
我们观察到I类和II类HLA抗原匹配显然不利于移植肾的长期存活。事实上，匹配的移植物在10年内丢失的比例与错配的移植物相同。我们还证明了：（1）在SNP -1082IL10位点为GG纯合子（高IL-10产生者）且I类HLA错配（但II类匹配）的患者可免受慢性排斥反应；（2）在SNP -33IL4位点为CC纯合子（低IL-4产生者）且I类HLA错配（无论II类是否匹配）的患者可免受慢性排斥反应。
