Favoino E, Favia I E, Vettori S, Vicenti C, Prete M, Valentini G, Perosa F
Department of Biomedical Sciences and Human Oncology (DIMO), Rheumatologic and Systemic Autoimmune Diseases Unit, University of Bari Medical School, Bari, Italy.
Department of Clinical and Experimental Internal Medicine 'F. Magrassi, A. Lanzara'-Rheumatology Section, Second University of Naples, Naples, Italy.
Clin Exp Immunol. 2015 Jul;181(1):100-9. doi: 10.1111/cei.12633. Epub 2015 May 10.
Human leucocyte antigen (HLA)-G has a tolerogenic function and could play a role in the pathogenesis of immune-mediated diseases, including systemic sclerosis (SSc). The aim of this study was to evaluate HLA-G serum expression (sHLA-G) and the HLA-G gene 14 base pairs (bp) insertion/deletion (del(-)/del(+)) polymorphism in patients with Ssc, to search for possible associations with clinical and laboratory variables. sHLA-G was measured by enzyme-linked immunosorbent assay (ELISA) in sera from 77 patients with SSc and 32 healthy donors (HD); the 14 bp del(-)/del(+) polymorphism was evaluated by polymerase chain reaction (PCR) amplification of peripheral blood mononuclear cells (PBMC) genomic DNA. Receiver operating characteristics (ROC) analysis identified the HLA-G cut-off that best discriminated dichotomized clinical and serological variables, that was subsequently employed to subdivide SSc patients into HLA-G high (HLA-G(+)) and low (HLA-G(-)) profile groups. sHLA-G were not statistically different between SSc patients and HD, nor between distinct SSc autoantibody subsets. Subdividing SSc patients by HLA-G positivity or negativity yielded significant differences for the modified Rodnan skin score (mRss) (P = 0.032), 'general' (P = 0.031) and 'kidney' (P = 0.028) Medsger severity scores (MSS) and disease activity index, and especially Δ heart/lung (P = 0.005). A worse 'general' MSS (P = 0.002) and Δ heart/lung (P = 0.011) were more frequent in the low sHLA-G group. These two variables and mRss were associated with sHLA-G levels at logistic regression analysis. Treatment had no influence on sHLA-G. Moreover, a higher frequency of scleredema was detected in the del(+)/del(+) than the del(-)/del(+) group (P = 0.04). These data suggest modulatory effects of sHLA-G on SSc. Prospective studies are needed to investigate a role in predicting the disease course.
人类白细胞抗原（HLA）-G具有免疫耐受功能，可能在包括系统性硬化症（SSc）在内的免疫介导疾病的发病机制中发挥作用。本研究的目的是评估SSc患者的HLA-G血清表达（sHLA-G）及HLA-G基因14碱基对（bp）插入/缺失（del(-)/del(+)）多态性，以寻找其与临床和实验室变量之间的可能关联。采用酶联免疫吸附测定（ELISA）法检测77例SSc患者和32例健康供者（HD）血清中的sHLA-G；通过聚合酶链反应（PCR）扩增外周血单个核细胞（PBMC）基因组DNA来评估14 bp del(-)/del(+)多态性。受试者工作特征（ROC）分析确定了能最佳区分二分临床和血清学变量的HLA-G临界值，随后据此将SSc患者分为HLA-G高表达（HLA-G(+)）组和低表达（HLA-G(-)）组。SSc患者与HD之间以及不同SSc自身抗体亚组之间的sHLA-G无统计学差异。根据HLA-G阳性或阴性对SSc患者进行分组后，改良Rodnan皮肤评分（mRss）（P = 0.032）、“总体”（P = 0.031）和“肾脏”（P = 0.028）Medsger严重程度评分（MSS）以及疾病活动指数存在显著差异，尤其是心脏/肺部差值（P = 0.005）。低sHLA-G组中“总体”MSS更差（P = 0.002）以及心脏/肺部差值更差（P = 0.011）的情况更为常见。在逻辑回归分析中，这两个变量和mRss与sHLA-G水平相关。治疗对sHLA-G无影响。此外，del(+)/del(+)组的硬化性水肿发生率高于del(-)/del(+)组（P = 0.04）。这些数据提示sHLA-G对SSc具有调节作用。需要进行前瞻性研究以探讨其在预测疾病进程中的作用。
