sHLA-Ⅰ研究进展

可溶性人类白细胞抗原 (sHLA)是存在于人类血液、尿液、淋巴液、乳汁等体液中的HLA分子 ,主要通过替代拚接、蛋白酶降解等途径产生。在体内可能参与机体的免疫调节 ,通过对其分布、功能的研究 ,将有助于移植排斥反应的监测 ,以及肿瘤、某些感染性疾病和自身免疫病的预防、诊断和治疗。     

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Human leucocyte antigen‐G (HLA‐G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14‐bp insertion/deletion (InDel) polymorphism in the 3′ untranslated region (3′‐UTR) of HLA‐G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA‐G (sHLA‐G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR] = 0.75; 95% confidence interval [CI]: 0.57–0.99; p = 0.040). Distribution of the 14‐bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR = 0.57; 95% CI = 0.33–0.99; p = 0.044) and the log‐additive model (OR = 0.76; 95% CI: 0.58–0.99; p = 0.044). The serum sHLA‐G level was significantly higher in the OSCC patients than those in the healthy controls (p < 0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA‐G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856–0.925, p < 0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA‐G levels than those with Ins/Del and Del/Del genotypes (p = 0.015). Furthermore, serum sHLA‐G levels were significantly increased with the increasing TNM stages of the OSCC patients (p = 0.017). Our findings revealed that the HLA‐G 14‐bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA‐G may act as a promising biomarker for noninvasive diagnosis of OSCC.     

可溶性人类白细胞抗原的研究进展与临床应用

可溶性人类白细胞抗原(sHLA)是存在于人类血清或其它体液中的HLA可溶性形式.近十年的研究显示sHLA在医学上意义重大.因其可参与调节免疫应答和诱导免疫耐受而被普遍重视,在器官移植、感染性疾病、肿瘤、自身免疫性疾病等病理状态下,血清中sHLA的含量均有明显变化.     

输供体骨髓对可溶性人类白细胞抗原-I的影响

目的：通过测定肾移植病人各处理组的可溶性人类白细胞抗原-1(sHLA-Ⅰ)含量,探讨sHLA-Ⅰ在排斥及预后中的意义。方法：80例肾移植病人分为四组,第一组术前用免疫抑制剂骁悉(MMF) 输供体骨髓;第二组术前用MMF;第三组术前输供体骨髓;第四组术前不用MMF也不输供体骨髓。术前、术后6月和12月采血测sHLA-Ⅰ含量。结果：第一组与第二组、第四组相比有极显著差异,第三组与第二、第四组有明显差异;第一、第三组术前术后相比有明显差异,且术后12月表现更为显著;第二、四组之间无差异。结论：输供体骨髓后,血清中sHLA-Ⅰ含量增加,sHLA-Ⅰ以阻断受者识别供体抗原,形成免疫耐受,这可能是移植后排异反应减少的原因之一;免疫抑制剂MMF对sHLA-Ⅰ影响不大,说明MMY、是通过非sHLA-Ⅰ途径起作用的。     

ORIGINAL ARTICLE: Differences in the Soluble HLA‐G Blood Serum Concentration Levels in Patients with Ovarian Cancer and Ovarian and Deep Endometriosis

Citation Mach P, Blecharz P, Basta P, Marianowski P, Skret‐Magierlo J, Kojs Z, Grabiec M, Wicherek L. Differences in the soluble HLA‐G blood serum concentration levels in patients with ovarian cancer and ovarian and deep endometriosis. Am J Reprod Immunol 2010 Problem The relationship between endometriosis and cancer has been widely discussed in the literature but is still not well clarified. Perhaps significantly, soluble human leukocyte antigen‐G (sHLA‐G) has been identified in the microenvironment of both ovarian cancer and endometrioma. The aim of this study has been to evaluate the sHLA‐G levels in the blood sera of women with deep endometriosis and ovarian endometrioma over the course of the menstrual cycle and to compare to the levels of sHLA‐G in the blood sera of women with ovarian cancer. Method of study In our study, we examined the blood sera obtained from 123 patients operated on because of ovarian cancer (65 cases), ovarian endometrioma (30 cases), and deep endometriosis (28 cases). We decided to compare the levels of sHLA‐G in patients with endometriosis to those found in patients with ovarian cancer with respect to the menstrual cycle phases. The sHLA‐G concentration level was measured by enzyme‐linked immunosorbent assay kit. Results The level of sHLA‐G concentration in the blood serum of patients with deep endometriosis fluctuates over the course of the menstrual cycle, and during the proliferative and secretory phases, it remains at a high level comparable to that found in patients with ovarian cancer. By contrast, the level of sHLA‐G concentration in the blood serum of patients with ovarian endometrioma fluctuates minimally over the course of the different menstrual cycle phases and, as in patients with ovarian cancer, it remains at high level during the proliferative phase. Conclusion sHLA‐G blood serum concentration levels would seem to provide important information regarding the degree of immune system regulation disturbance in both ectopic endometrial cells and the cancer cell suppressive microenvironment.     

输血相关免疫调节机制研究进展

同种异体输血(allogenic blood transfusion,ABT)发挥临床治疗作用的同时,也会发生很多免疫相关的副作用,如术后感染率上升、恶性肿瘤切除复发率增加等。血制品中的同种异基因单核细胞表面的CD200分子、白细胞及储存过程中白细胞脱落的sHLA和sFasL、血清中的生物活性分子等与输血相关免疫调节(transfusion-relatedimmunomodulation,TRIM)的发生均有一定联系。临床对照试验,实验室研究及动物模型显示:克隆删除、诱导无能、免疫抑制是TRIM发生的效应机制。本文就TRIM的发生机制、诱导TRIM发生的介质的研究进展进行了综述。     

Granulocytes and monocytes apheresis induces upregulation of TGFβ1 in patients with active ulcerative colitis: A possible involvement of soluble HLA‐I

Granulocyte and monocyte apheresis has been used in different immune‐mediated disorders, mainly inflammatory bowel diseases. The removal of activated leukocytes and several additional immunomodulatory mechanisms have been so far suggested to explain the anti‐inflammatory effects of the treatment. Recent data indicate that, during centrifugation based apheresis, sHLA‐I adsorbed to plastic circuits is able to induce TGFβ₁ production in activated leukocytes. On these bases, the present study was aimed at analyzing if this model could be applied to a noncentrifugation based apheresis, such as granulocyte and monocyte apheresis. Ten patients with ulcerative colitis were enrolled. Every patient received 5 weekly apheresis treatments. Cellulose acetate beads removed from the column post‐GMA were stained by fluorescent anticlass I mAb and examined by fluorescent microscope. Moreover, sFasL plasma concentration, TGFβ₁ plasma levels, and the percentage of TGFβ₁ positive neutrophils were evaluated before and immediately after each single apheresis. Immunofluorescent images revealed a homogeneous layer of a sHLA‐I adsorbed to the surface of the beads recovered following the procedure. sFasL plasma concentration progressively increased both following the procedures and during inter‐procedure periods. Consistently, also TGFβ₁ plasma levels and the percentage of TGFβ₁ positive neutrophils increased during the procedures with a meaningful relationship with sFasL plasma levels. Taken together, these findings suggest that the immunosuppressive effects attributed to granulocyte and monocyte apheresis might depend, at least in part, on the sensitivity of activated leucocytes to the bioactivity of sHLA‐I molecules. J. Clin. Apheresis 32:49–55, 2017. © 2016 Wiley Periodicals, Inc.     

血清可溶性人白细胞抗原G测定在诊断亚临床绒毛膜羊膜炎中的意义

目的探讨孕妇血清可溶性人白细胞抗原G（sHLA-G）测定在诊断妊娠合并亚临床绒毛膜羊膜炎中的意义。方法选取早产及胎膜早破孕产妇115例及正常足月分娩孕产妇40例,通过运用双抗体夹心酶联免疫吸附（ELISA）法检测上述研究对象血清中sHLA-G的水平,同时用散射比浊法测定其中C反应蛋白（CRP）含量,最后对所有产后胎膜进行病理检查,判断有无绒毛膜羊膜炎。结果①通过对产后胎膜组织进行病理检查,共检测出绒毛膜羊膜炎患者70例,作为研究组,另外85例无绒毛膜羊膜炎患者作为对照组;②研究组血清中sHLA-G的水平平均为（46.52±13.75）U/ml,显著高于对照组（28.48±10.76U/ml）,差异有统计学意义（P〈0.001）;③研究组血清中CRP的水平平均为（13.39±12.48）mg/L,显著高于对照组（5.49±5.45mg/L）,差异有统计学意义（P〈0.001）;④用ROC曲线分析：血清sHLA-G检测绒毛膜羊膜炎的最佳临界值为36.09U/ml,诊断敏感性77.1%,特异性75.3%,曲线下面积0.847,明显优于CRP（敏感性68.6%,特异性68.2%,曲线下面积0.739,最佳临界值为7.5mg/L）。结论发生绒毛膜羊膜炎时,母血中sHLA-G的水平升高,与CRP相比,有更高的敏感性和特异性,提示sHLA-G是诊断亚临床绒毛膜羊膜炎的较理想的血清学指标。     

系统性红斑狼疮患者sHLA—Ⅰ类分子的定量检测及意义

目的定量检测湖南SLE患者的sHLA-Ⅰ类分子水平。方法采用ELISA双抗夹心法检测血浆的sHLA-Ⅰ类分子水平。结果血浆sHLA-Ⅰ类分子水平26例活动期SLE患者为970.46±342.79μg/L,29例非活动期SLE患者为719.93±102.24μg/L,37例正常人为558.18±189.69μg/L,与正常人相比SLE活动期(P＜0.01)和非活动期(P＜0.05)均明显增高,且活动期明显高于非活动期(P＜0.01)。结论活动期和非活动期SLE患者血浆的sHLA-Ⅰ类分子水平明显增高,且活动期增高更显著。