a Institute of Immunology, Faculty of Medicine , Comenius University in Bratislava , Bratislava , Slovakia.
b National Transplantation Organisation , Bratislava , Slovakia.
Immunol Invest. 2019 Aug;48(6):644-658. doi: 10.1080/08820139.2019.1610888. Epub 2019 May 16.
: Human leukocyte antigen G (HLA-G) belongs to nonclassical HLA I molecule involving in the suppression of immune response. Besides its profound effect to induce fetal tolerance, HLA-G expression has been associated with allograft acceptance. For the regulation of HLA-G levels, polymorphic sites within the 3' untranslated region (3'UTR) are of crucial importance. The aim of the study was to analyze the association between several 3'UTR variants (+3003T/C, +3010C/G, +3027C/A, +3035C/T, +3142G/C, +3187A/G, and +3196C/G), soluble HLA-G (sHLA-G) level, and kidney graft outcome in the Slovak Caucasian population. : We investigated 69 kidney transplant recipients (45 males, 24 females) of age 27-65 years. Out of this group, 37 recipients developed acute rejection that was biopsy proven. Recipient's plasma was obtained at 1 day before transplantation and analyzed by ELISA. The 3'UTR polymorphisms were typed by direct sequencing. : In the recipients with stable allograft function, significantly higher values of sHLA-G were found in the homozygous +3010GG, +3142CC, +3187GG, and +3196CC carriers in comparison to the acute rejection recipients (P = 0.01-0.05). : The study demonstrated genetic association between 3'UTR variants and sHLA-G level in kidney recipients leading to graft acceptance. We suggest to monitor the pretransplantation sHLA-G level as additional marker to predict kidney graft outcome. AMR: Antibody-mediated rejection; APC: antigen-presenting cell; CD: cluster of designation; del: deletion; HLA: human leukocyte antigen; ILT: immunoglobulin-like transcript; ins: insertion; KIR: killer-cell immunoglobulin-like receptor; NK: natural killer; sHLA-G: soluble HLA-G; SNP: single nucleotide polymorphism; TCMR: T cell-mediated rejection; URR: upstream regulatory region; UTR: untranslated region.
人类白细胞抗原 G（HLA-G）属于非经典 HLA I 分子，参与免疫反应的抑制。除了其对诱导胎儿耐受的深远影响外，HLA-G 的表达还与同种异体移植物的接受有关。为了调节 HLA-G 水平，3'非翻译区（3'UTR）内的多态性位点至关重要。本研究旨在分析斯洛伐克白种人群中几个 3'UTR 变体（+3003T/C、+3010C/G、+3027C/A、+3035C/T、+3142G/C、+3187A/G 和 +3196C/G）、可溶性 HLA-G（sHLA-G）水平与肾移植结局之间的关系。
我们研究了 69 名年龄在 27-65 岁的肾移植受者（45 名男性，24 名女性）。其中 37 名受者发生了经活检证实的急性排斥反应。在移植前 1 天采集受者的血浆，并通过 ELISA 进行分析。3'UTR 多态性通过直接测序进行分型。
在具有稳定移植物功能的受者中，与急性排斥反应受者相比，纯合子+3010GG、+3142CC、+3187GG 和+3196CC 携带者的 sHLA-G 值显著更高（P=0.01-0.05）。
该研究表明，3'UTR 变体与肾移植受者 sHLA-G 水平之间存在遗传关联，导致移植物接受。我们建议在移植前监测 sHLA-G 水平作为预测肾移植结局的附加标志物。
抗体介导的排斥反应；APC：抗原呈递细胞；CD：集群设计；del：缺失；HLA：人类白细胞抗原；ILT：免疫球蛋白样转录物；ins：插入；KIR：杀伤细胞免疫球蛋白样受体；NK：自然杀伤细胞；sHLA-G：可溶性 HLA-G；SNP：单核苷酸多态性；TCMR：T 细胞介导的排斥反应；URR：上游调控区；UTR：非翻译区。
