人白细胞抗原G 14 bp插入/缺失多态性和血浆可溶性人白细胞抗G原表达
吴凤霞,武丽君,罗雄燕,杨明辉,刘宁涛,库尔班江,谢传美,宋小芸,唐中,张国元,周京国,赵岩,曾小峰,袁国华吴凤霞、武丽君、罗雄燕、杨明辉、刘宁涛、库尔班江、谢传美,四川南充 川北医学院风湿免疫研究所,637000;武丽君、库尔班江、宋小芸,新疆维吾尔自治区人民医院风湿科;刘宁涛,遂宁市中心医院风湿科;赵岩、曾小峰,中国医学科学院 北京协和医学院 北京协和医院风湿科
基金项目:卫生部重大疾病研究资助项目(2008BA159B02)
摘 要:目的 检测系统性红斑狼疮(SLE)患者人白细胞抗原G(HLA-G)14 bp插入/缺失(ins/del)多态性和血浆可溶性HLA-G(sHLA-G)水平,并分析它们与SLE的关联性。方法 聚合酶链式反应(PCR)检测231例SLE患者及367名健康体检者的HLA-G 14 bp ins/del多态性的基因型分布,酶联免疫吸附法(ELISA)检测其中96例SLE患者及74名健康体检者血浆sHLA-G水平。结果 HLA-G 14 bp ins/del多态性位点和基因型频率分布在正常人组和SLE组均无统计学意义(P均>0.05),血浆sHLA-G水平在SLE患者组为(230.2±192.2)U/ml,明显高于正常人组的(118.3±38.1)U/ml(P=0.0001);血浆sHLA-G水平增高的SLE患者易出现中枢神经系统受累(P=0.007),且较血浆sHLA-G水平正常的患者病情更重(P=0.027)。进一步分析血浆sHLA-G水平增高和正常SLE患者的HLA-G 14 bp ins/del多态性位点和基因型分布,未发现两组间有差异(P=0.675)。结论 血浆sHLA-G水平在SLE患者中明显增高提示sHLA-G可能参与到SLE发病机制中,其水平高低主要取决于SLE病情严重性及活动性,而与HLA-G 14 bp ins/del多态性无关。
关键词:红斑狼疮,系统性; HLA抗原; 基因型
HLA-G 14 bp ins/del polymorphism and expression of plasma soluble HLA-G in patients with systemic lupus erythematosus
WU Feng-xia,WU Li-jun,LUO Xiong-yan,YANG Ming-hui,LIU Ning-tao, KUER Ban-jiang,XIE Chuan-mei,SONG Xiao-yun,TANG Zhong,ZHANG Guo-yuan,ZHOU Jing-guo,ZHAO Yan,ZENG Xiao-feng,YUAN Guo-hua.Institute of Rheumatology and Immunology,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China
Abstract:Objective To determine the association of HLA-G 14 bp insertion/deletion polymorphism and plasma soluble HLA-G(sHLA-G)levels with systemic lupus erythematosus(SLE). Methods Polymerase chain reaction(PCR)was performed to detect the genotypes of HLA-G 14 bp ins/del polymorphism in 231 SLE patients and 367 healthy controls,and soluble HLA-G(sHLA-G)levels were determined by enzyme-linked immunosorbent assay in 96 SLE patients and 74 healthy controls. Results No significant differences were found in HLA-G 14 bp ins/del allelic frequencies and genotype distributions between SLE patients group and the control group(P>0.05). However,plasma concentration of sHLA-G was significant higher in SLE patients than that in healthy controls(230.2±192.2)U/ml vs.(118.3±38.1)U/ml,P=0.0001). Moreover,the patients with increased levels of sHLA-G had higher incidence of central nervous system involvement(P=0.007)and more severe disease activity(P=0.027)in comparison with patients with normal plasma sHLA-G levels. Finally,analysis of HLA-G 14 bp ins/delpolymorphism in patients with increased sHLA-G levels revealed that there was not different from that in patients with normal sHLA-G levels(P=0.675). Conclusions The increased production of sHLA-G indicates that sHLA-G may play an important role in the pathogenesis of SLE,the expression of sHLA-G may be associated with disease activity and severity of lupus patients,but be independence of HLA-G 14 bp ins/del polymorphism.
Key words:Lupus erythematosus,systemic; HLA antigens; Genotype
参考文献:
[1] Apps R,Gardner L,Moffett A. A critical look at HLA-G. Trends Immunol,2008,29(7):313-321.[PubMed]
[2] Rizzo R,Hviid TV,Govoni M,et al. HLA-G genotype and HLA-G expression in systemic lupus erythematosus:HLA-G as a putative susceptibility gene in systemic lupus erythematosus. Tissue Antigens,2008,71(6):520-529.[PubMed]
[3] Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum,1997,40(9):1725.[PubMed]
[4] Bombardier C,Gladman DD,Urowitz MB,et al. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum,1992,35(6):630-640.[PubMed]
[5] Hviid TV,Rizzo R,Melchiorri L,et al. Polymorphism in the 5′ upstream regulatory and 3′ untranslated regions of the HLA-G gene in relation to soluble HLA-G and IL-10 expression. Hum Immunol,2006,67(1/2):53-62.[PubMed]
[6] Rouas-Freiss N,Marchal RE,Kirszenbaum M,et al. The alpha1 domain of HLA-G1 and HLA-G2 inhibits cytotoxicity induced by natural killer cells:is HLA-G the public ligand for natural killer cell inhibitory receptors?Proc Natl Acad Sci U S A,1997,94(10):5249-5254.[PubMed]
[7] Lindaman A,Dowden A,Zavazava N. Soluble HLA-G molecules induce apoptosis in natural killer cells. Am J Reprod Immunol,2006,56(1):68-76.[PubMed]
[8] Shiroishi M,Tsumoto K,Amano K,et al. Human inhibitory receptors Ig-like transcript 2(ILT2)and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci U S A,2003,100(15):8856-8861.[PubMed]
[9] Contini P,Ghio M,Poggi A,et al. Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. Eur J Immunol,2003,33(1):125-134.[PubMed]
[10] Baricordi OR,Stignani M,Melchiorri L,et al. HLA-G and inflammatory diseases. Inflamm Allergy Drug Targets,2008,7(2):67-74.[PubMed]
[11] Harley JB,Kelly JA,Kaufman KM. Unraveling the genetics of systemic lupus erythematosus. Springer Semin Immunopathol,2006,28(2):119-130.[PubMed]
[12] Kono DH,Theofilopoulos AN. Genetics of SLE in mice. Springer Semin Immunopathol,2006,28(2):83-96.[PubMed]
[13] Müller-Hilke B,Mitchison NA. The role of HLA promoters in autoimmunity. Curr Pharm Des,2006,12(29):3743-3752.[PubMed]
[14] Veit TD,Cordero EA,Mucenic T,et al. Association of the HLA-G 14 bp polymorphism with systemic lupus erythematosus. Lupus,2009,18(5):424-430.[PubMed]
[15] Chen XY,Yan WH,Lin A,et al. The 14 bp deletion polymorphisms in HLA-G gene play an important role in the expression of soluble HLA-G in plasma. Tissue Antigens,2008,72(4):335-341.[PubMed]
[16] Rosado S,Perez-Chacon G,Mellor-Pita S,et al. Expression of human leukocyte antigen-G in systemic lupus erythematosus. Hum Immunol,2008,69(1):9-15.[PubMed]
期刊存档









