银屑病患者外周血单一核细胞CTLA4表达及基因多态性分析

目的：了解银屑病患者外周血单一核细胞（PBMC）细胞毒T细胞分子4（CTLA4）表达状况及基因多态性。方法：选择临床和／或病理诊断明确的银屑病患者33例作为CTLA4 mRNA和蛋白表达研究对象，另选133例患者作为CTLA4基因多态性分析对象，并以正常人作平行对照。分别用原位杂交、免疫组化、PCR等方法检测CTLA4 mRNA、蛋白表达、第一外显子和3‘末端非翻译区（AT）n重复序列，对PCR扩增产物进行单链构象多态性、限制性片段长度多态性及基因序列分析。结果：与正常人组相比，银屑病患者PBMC经金黄色葡萄球菌肠毒素B刺激后CTLA4 mRNA、蛋白表达强度显著减弱，且无一定规律；分析发现，CTLA4第一外显子第49位点G和3‘末端非翻译区106bp等位基因与银屑病发生存在显著关联。结论：银屑病患者CTLA4基因转录和表达存在缺陷，且这一缺陷与CTLA4基因多态性存在关联，提示CTLA4基因可能是导致银屑病自身免疫反应发生的侯选基因之一。

Expression and Gene Polymorphism of Cytotoxic T Lymphocyte-Associated Molecule 4 on Peripheral Blood Mononuclear Cells from Patients with Psoriasis

Objective To investigate the status of expression and gene polymorphism of cytotoxic T lymphocyte-associated molecule4(CTLA4)on peripheral blood mononuclear cells(PBMCs)from patients with psoriasis.Methods Expression of CTLA4mRNA/antigen and polymorphism of CTLA4gene were analyzed in33and133patients with psoriasis confirmed clinically and/or pathologically,respectively.Expression of CT-LA4mRNA and antigen was detected by in situ hybridization and immmunohistochemistry.CTLA4exon1and3'untranslated region were amplified by polymerase chain reaction(PCR)and the amplified products were identified by single-stand conformation polymorphism(SSCP),restriction fragment length polymorphism(RFLP)or sequencing.Results Expression of both mRNA and antigen of CTLA4was significantly weaker on PBMCs induced by staphytococcal enterotoxin B(SEB)in patients with psoriasis than that in normal con-trols,without a regular pattern.The guanine49on exon1in association with fragment106bp of3'untranslat-ed region was shown to be linked to the susceptibility of psoriasis.Conclusion Defective translation and ex-pression of CTLA4take place in patients with psoriasis,which is possibly related to the polymorphism of CT-LA4.Our results suggest that CTLA4may be one of the candidate genes which cause autoimmunity in psoria-sis.