Borghi Alessandro, Rizzo Roberta, Corazza Monica, Bertoldi Alberto Maria, Bortolotti Daria, Sturabotti Giulia, Virgili Annarosa, Di Luca Dario
Department of Medical Sciences, Section of Dermatology, University of Ferrara, Ferrara, Italy.
Dermatol Ther. 2014 Sep-Oct;27(5):284-9. doi: 10.1111/dth.12140. Epub 2014 Jun 9.
Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule that exerts an immunosuppressive function. A 14-base pair (bp) sequence insertion/deletion (INS/DEL) polymorphism in the exon 8 at the 3' untranslated region (UTR) modifies mRNA stability and protein production and has been shown to concur with efficacy of pharmacological treatments in immune-mediated conditions. The aim of this study was to assess for the first time the correlation between HLA-G 14-bp INS/DEL polymorphism with the response to systemic therapy in psoriatic patients. We retrospectively analyzed the HLA-G 14-bp INS/DEL polymorphism of HLA-G gene in patients with moderate to severe plaque psoriasis: 21 treated with acitretin, 16 with cyclosporine, 11 with anti-TNF-α. Patients who reached PASI 75 at weeks 10-16 were considered responders. Among patients treated with acitretin, we observed a significantly increased frequency of the HLA-G DEL allele and of the DEL/DEL genotype in responder patients when compared with nonresponders. An association between HLA-G genotype and response to cyclosporine and biologics was not found. The significant association between HLA-G 14-bp DEL allele and 14-bp DEL/DEL genotype and acitretin clinical outcome may suggest an advantage of this allele and propose this HLA-G polymorphism as a potential marker of response to acitretin in psoriatic patients.
人类白细胞抗原-G(HLA-G)是一种发挥免疫抑制功能的非经典HLA I类分子。3'非翻译区(UTR)外显子8中的14碱基对(bp)序列插入/缺失(INS/DEL)多态性会改变mRNA稳定性和蛋白质产生,并且已被证明与免疫介导疾病的药物治疗疗效相关。本研究的目的是首次评估HLA-G 14-bp INS/DEL多态性与银屑病患者全身治疗反应之间的相关性。我们回顾性分析了中度至重度斑块状银屑病患者HLA-G基因的HLA-G 14-bp INS/DEL多态性:21例接受阿维A治疗,16例接受环孢素治疗,11例接受抗TNF-α治疗。在第10 - 16周达到PASI 75的患者被视为反应者。在接受阿维A治疗的患者中,与无反应者相比,我们观察到反应者患者中HLA-G DEL等位基因和DEL/DEL基因型的频率显著增加。未发现HLA-G基因型与环孢素和生物制剂反应之间的关联。HLA-G 14-bp DEL等位基因和14-bp DEL/DEL基因型与阿维A临床结果之间的显著关联可能表明该等位基因具有优势,并提示这种HLA-G多态性可作为银屑病患者对阿维A反应的潜在标志物。