The role of immune mechanisms in alcoholic and nonalcoholic steatohepatitis: a 2015 update

So far, innate immune mechanisms have been recognized as the main responsible for the evolution of both alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). However, increasing evidence points toward the possible role of adaptive immune responses, as an additional factor in promoting hepatic inflammation in steatohepatitis. In this article, we discuss recent data involving circulating antibodies and lymphocyte-mediated responses in sustaining the progression of ASH and NASH to fibrosis, as well as the possible mechanisms implicated in favoring the onset of adaptive immunity in the setting of steatohepatitis.     

反应性关节炎患者关节液T细胞克隆研究

目的比较来自反应性关节炎(ReA)患者的关节液的CD8^ T细胞克隆、CD4^ T细胞克隆和γδ^ T细胞克隆的细胞因子表达谱，探讨ReA的免疫机制。方法用含56种细胞因子基因的cDNA微阵列筛选来自3个ReA患者的关节液的3个CD8^ T细胞克隆、3个CD4^ T细胞克隆和3个γδ^ T细胞克隆的差异表达基因。结果微阵列研究显示，CD8^ 和CD4^ T细胞克隆中有编码干扰素(IFN)-γ和肿瘤坏死因子(TNF)-α转录物的表达。15个微阵列试验中有14个可以用反转录-聚合酶链反应(RT-PCR)技术证实有这些细胞因子的表达。CD4^ 细胞持续表达淋巴毒素-α(LT-α)和粒细胞-巨噬细胞集落刺激因子(GM—CSF)。但是γδ^ T细胞主要表达转化生长因子(TGF)-β2和GM—CSF。结论CD8^ 和CD4^ T细胞克隆的细胞因子表达谱主要为Th1，而γδ^ T细胞较少表达促炎症细胞因子，似为Th3模式。ReA患者关节液的T淋巴细胞克隆显示了不同的细胞因子表达谱，它反映了不同的T细胞在发病机制中有不同的作用。     

Diagnostic value of screening tests in subgroups of women with recurrent pregnancy loss

Objective: To evaluate the diagnostic value of screening laboratory tests in women who had recurrent pregnancy loss (RPL).

Methods: A total of 252 women with RPL managed in our tertiary referral research and education hospital were included in the study. Risk factors recorded involved age, gravidity, parity, number of prior live births, number of pregnancy losses, and thrombophlia tests. The cases were divided into three different groups and each group was analyzed separately.

Results: There was no statistically significant difference between the first and second groups in terms of clinical and laboratory parameters (p?>?0.05). In the third group, there was a statistically significant difference among cases in terms of parity, gravidity, number of pregnancy losses, serum AT III levels, APCR, and age of the women. According to the logistic regression model, odds ratios (95% CI) were 6.116 (3.797–9.852), 5.665 (2.657–12.079), 4.763 (3.099–7.321), 4.729 (3.080–7.260), 2.820 (1.836–4.333), and 1.911 (1.232–2.965), respectively.

Conclusions: We do not recommend the screening of all women with RPL, but in women with high parity and those who had prior live birth pregnancies, increased AT III, and APCR may be diagnostic markers for subsequent pregnancy loss.     

A PRIM approach to predictive‐signature development for patient stratification

Patients often respond differently to a treatment because of individual heterogeneity. Failures of clinical trials can be substantially reduced if, prior to an investigational treatment, patients are stratified into responders and nonresponders based on biological or demographic characteristics. These characteristics are captured by a predictive signature. In this paper, we propose a procedure to search for predictive signatures based on the approach of patient rule induction method. Specifically, we discuss selection of a proper objective function for the search, present its algorithm, and describe a resampling scheme that can enhance search performance. Through simulations, we characterize conditions under which the procedure works well. To demonstrate practical uses of the procedure, we apply it to two real‐world data sets. We also compare the results with those obtained from a recent regression‐based approach, Adaptive Index Models, and discuss their respective advantages. In this study, we focus on oncology applications with survival responses. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.     

强直性脊柱炎患者细胞毒性T淋巴细胞变化

目的 探讨细胞毒性T淋巴细胞(T-lymphocytes,Tc)在强直性脊柱炎(ankylosing spondylitis,AS)患者中的表达变化.方法 筛选42例AS患者作为研究对象(病例组),20例同时期健康查体者作为对照(对照组).检测2组血小板计数、红细胞沉降率(erythrocyte sedimentation rate,ESR)、C反应蛋白(C-neactveprotein,CRP)水平并记录强直性脊柱炎病情活动指数调查表(bath ankylosing spondylitis disease activity index,BASDAI)评分.应用流式细胞仪检测外周血中淋巴细胞表型(CD3+CD8+)、胞浆内细胞因子γ干扰素、白细胞介素4的表达.采用t检验分析两组间外周血中Tc、Tc1、Tc2、Tc1/Tc2比值的差异;相关分析采用Pearson检验.结果 病例组与对照组外周血中Tc分别为(21.22±4.27)％ vs (14.23±4.15)％ (t=6.177,P＜0.01),Tc1分别为(0.35±0.08)％vs(1.45±0.27)％(t=24.640,P＜0.01),Tc2分别为(0.53±0.12)％vs(0.41±0.12)％(t=3.608,P＜0.01),Tc1/Tc2比值分别为0.72±0.29vs3.93±1.63(t=6.431,P＜0.01).相关分析显示AS患者外周血中Tc、Tc1、Tc2、Tc1/Tc2比值与血小板计数、ESR、CRP、BASDAI均无相关性.结论 AS患者外周血中Tc1细胞减少,Tc2细胞增多,的确存在Tc1/Tc2细胞的失衡,而且是Tc2细胞占优势.     

悬浮红细胞对CD4+CD25+Treg细胞分化的影响

目的 体外观察悬浮红细胞对异体T淋巴细胞向CD4+ CD25+ Treg细胞分化的影响.方法 采用Ficoll密度梯度离心法和免疫磁珠法从人外周血中分离纯化出CD3+T淋巴细胞,给予CD3/CD28抗体刺激,并分别与异体非去白悬浮红细胞或去白悬浮红细胞混合培养72 h.采用流式细胞仪检测各组培养体系中CD4+ CD25+Treg细胞的比例.采用实时荧光定量PCR检测各组Foxp3 mRNA的表达情况.采用酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)法检测各组细胞上清中促炎细胞因子[白细胞介素2(interleukin-2,IL-2)和干扰素γ(interferon-γ,IFN-γ)]和抗炎细胞因子[白细胞介素10(interleukin-10,IL-40)和转化生长因子β(transforming growth factor beta,TGF-β)]的水平.结果 与阴性对照组(细胞培养液组)比较,非去白悬浮红细胞和去白悬浮红细胞组CD4+ CD25+ Treg细胞比例明显增加,功能基因Foxp3 mRNA表达也明显增高;1L-2和IFN-γ促炎细胞因子分泌减少,IL-10和TGF-β抗炎细胞因子分泌增多(P＜0.01).而与去白悬浮红细胞比较,非去白悬浮红细胞作用更加明显(P＜0.05).结论 悬浮红细胞可能通过调节促炎/抗炎细胞因子平衡诱导异体T淋巴细胞向CD4+ CD25+ Treg分化,而悬浮红细胞内残留的白细胞可能在其中起了关键作用.     

胆道闭锁肝纤维化研究进展

胆道闭锁（BA）是严重危及婴幼儿生命健康的消化系统疾病之一,晚期肝脏纤维化是导致患儿死亡的主要原因。在胆道闭锁发病过程中,病毒感染可诱导一系列免疫和炎症反应,导致调节性T细胞（Treg细胞）减少,CD14表达增高,多种炎症通路以及转化生长因子-β（TGF-β）/Smad2/3促纤维化通路被激活。激活的通路产生大量炎性介质损伤肝细胞和胆管细胞,释放各种促炎因子、氧代谢产物和细胞因子,进一步加重肝、胆系统损伤造成肝细胞内环境失衡,失衡的内环境伴随肝实质细胞、肝巨噬细胞、肝内聚集的炎性细胞等发生适应性变性、坏死、增生,导致肝星形细胞（HSCs）激活,HSCs转化为成纤维细胞,促进肝纤维化进程。免疫、炎症损伤、促纤维化通路是导致胆道闭锁肝纤维化肝硬化的三大重要因素。     

Esophageal lichen planus: Current knowledge,challenges and future perspectives

Lichen planus (LP) is a frequent, chronic inflammatory disease involving the skin, mucous membranes and/or skin appendages. Esophageal involvement in lichen planus (ELP) is a clinically important albeit underdiagnosed inflammatory condition. This narrative review aims to give an overview of the current knowledge on ELP, its prevalence, pathogenesis, clinical manifestation, diagnostic criteria, and therapeutic options in order to provide support in clinical management. Studies on ELP were collected using PubMed/Medline. Relevant clinical and therapeutical characteristics from published patient cohorts including our own cohort were extracted and summarized. ELP mainly affects middle-aged women. The principal symptom is dysphagia. However, asymptomatic cases despite progressed macroscopic esophageal lesions may occur. The pathogenesis is unknown, however an immune-mediated mechanism is probable. Endoscopically, ELP is characterized by mucosal denudation and tearing, trachealization, and hyperkeratosis. Scarring esophageal stenosis may occur in chronic courses. Histologic findings include mucosal detachment, T-lymphocytic infiltrations, epithelial apoptosis (Civatte bodies), dyskeratosis, and hyperkeratosis. Direct immuno-fluorescence shows fibrinogen deposits along the basement membrane zone. To date, there is no established therapy. However, treatment with topical steroids induces symptomatic and histologic improvement in two thirds of ELP patients in general. More severe cases may require therapy with immunosuppressors. In symptomatic esophageal stenosis, endoscopic dilation may be necessary. ELP may be regarded as a precancerous condition as transition to squamous cell carcinoma has been documented in literature. ELP is an underdiagnosed yet clinically important differential diagnosis for patients with unclear dysphagia or esophagitis. Timely diagnosis and therapy might prevent potential sequelae such as esophageal stenosis or development of invasive squamous cell carcinoma. Further studies are needed to gain more knowledge about the pathogenesis and treatment options.