Fate of full‐house immunofluorescence staining in renal allograft: A case report

Here, we report the case of a patient with renal allograft with full‐house immunofluorescence staining in the zero‐hour biopsy. Full‐house immunofluorescence staining is a well‐known characteristic of lupus nephritis. Previous studies have reported patients with full‐house immunofluorescence staining, but without other symptoms or serological findings; this condition is referred to as full‐house nephropathy. We identified only one case out of 2203 zero‐hour biopsies over 13 years. Zero‐hour biopsy presented no glomerular changes but showed full‐house immunofluorescence staining. Electron microscopy revealed a nonorganized electron‐dense deposit mainly in the mesangial lesion. Systemic lupus erythematosus (SLE)‐associated antibodies were negative, and complement deficiency was not observed in the donor patients. Deposition of immunoglobulin and complement levels markedly decreased within 1–3 years post transplantation. Neither donor nor recipient developed clinical or biological features of SLE; they showed good renal prognosis.     

Immune checkpoints and the regulation of tolerogenicity in dendritic cells: Implications for autoimmunity and immunotherapy

The immune system is responsible for defending the host from a large variety of potential pathogens, while simultaneously avoiding immune reactivity towards self-components. Self-tolerance has to be tightly maintained throughout several central and peripheral processes; immune checkpoints are imperative for regulating the immunity/tolerance balance. Dendritic cells (DCs) are specialized cells that capture antigens, and either activate or inhibit antigen-specific T cells. Therefore, they play a key role at inducing and maintaining immune tolerance. DCs that suppress the immune response have been called tolerogenic dendritic cells (tolDCs). Given their potential as a therapy to prevent transplant rejection and autoimmune damage, several strategies are under development to generate tolDCs, in order to avoid activation and expansion of self-reactive T cells. In this article, we summarize the current knowledge relative to the main features of tolDCs, their mechanisms of action and their therapeutic use for autoimmune diseases. Based on the literature reviewed, autologous antigen-specific tolDCs might constitute a promising strategy to suppress autoreactive T cells and reduce detrimental inflammatory processes.     

Microbe-metabolite-host axis,two-way action in the pathogenesis and treatment of human autoimmunity

The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.     

红景天苷上调HIF-1α减轻高糖诱导的大鼠肾小球内皮细胞损伤

目的:观察体外不同浓度葡萄糖对大鼠肾小球内皮细胞(rRGECs)表达低氧诱导因子1α(HIF-1α)、血管内皮生长因子A(VEGFA)及血管内皮钙黏素(VE-cadherin)的影响,探讨红景天苷减轻高糖诱导rRGECs损伤的作用及可能相关机制。方法:体外培养rRGECs,分为正常糖组、高糖(20、30和50 mmol/L)组、高渗组及红景天苷+高糖组。采用MTT法检测rRGECs的活力;RT-qPCR法检测rRGECs内HIF-1α、VEGFA及VE-cadherin的mRNA表达;Western blot法检测rRGECs内HIF-1α蛋白的表达。结果:与正常糖组相比,培养24 h后,高糖(20mmol/L)组rRGECs HIF-1α的mRNA及蛋白表达均上调(P 0.05);培养120 h后,高糖组HIF-1αmRNA表达下调(P 0.05)。与正常糖组相比,培养24 h和120 h后,高糖组rRGECs内VE-cadherin的mRNA表达下调(P 0.05)。与正常糖组相比,培养24 h后,高糖组rRGECs内VEGFA的mRNA表达上调(P 0.05);培养120 h后,高糖组rRGECs内VEGFA的mRNA表达下调(P 0.05)。与正常糖组相比,培养24 h和120 h后,高渗组rRGECs内HIF-1α、VE-cadherin及VEGFA的mRNA表达无变化。与高糖组相比,培养24 h后,红景天苷(50μmol/L)组rRGECs的活力增加(P 0.01),且细胞内HIF-1α和VE-cadherin的mRNA及HIF-1α蛋白表达均上调(P 0.05)。结论:体外高糖培养能影响rRGECs表达HIF-1α,可能与细胞活力、葡萄糖的浓度、作用时间及HIF/VEGF通路有关。红景天苷能减轻高糖诱导的rRGECs损伤,其机制可能与增加rRGECs内HIF-1α的表达有关。     

2型糖尿病肾病患者红细胞免疫功能与脂质过氧化的关系

目的：探讨了2型糖尿病肾病患者红细胞免疫功能的变化及其与脂质过氧化的关系。方法：应用红细胞酵母花环法对34例2型糖尿病肾病患者进行了红细胞免疫功能和化学比色法测定血清丙二醛（MDA）、超过氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）含量,并与35名正常健康人作比较。结果：2型糖尿病患者红细胞免疫复合物（RBC-IC）花环率和MDA水平明显升高（P〈0.05～0.01）,而红细胞C3b受体（RBCc3b-RR）、SOD、GSH-PX水平显著低于正常（P〈0.01）。相关分析显示：RBCc3b花环与MDA呈显著负相关（r=-0.4012,P〈0.05）,RBC-ICR与MDA呈显著正相关（r=0.5928,P〈0.01）。结论：2型糖尿病患者红细胞免疫功能降低与活性氧代谢紊乱密切相关。     

缬沙坦对2型糖尿病肾病的疗效观察

目的 观察缬沙坦对2型糖尿病肾病患者尿白蛋白排泄率（UAER）的影响。方法 49例2型糖尿病肾病（DN）患者随机分为观察组（25例）和对照组（24例）。全部对象均给予常规糖尿病药物治疗，观察组加予缬沙坦80mg／d，与对照组比较12周前后UAER的变化。结果 观察组UAER明显下降，显著优于对照组。结论 血管紧张素受体拮抗剂（缬沙坦）有益于减少糖尿病肾病患者微量白蛋白尿排泄，对DN有延缓进展的作用。     

内蒙古包头地区汉族人群TNF-α-308位点基因多态性与IgA肾病的相关性研究

目的：了解内蒙古包头地区汉族人群IgA肾病患者肿瘤坏死因子α（TNF-α）-308位点基因型的分布特点。方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测97例IgA肾病患者和73例正常人的TNF-α基因型。结果：IgA肾病患者组中TNF-α基因G/A多态GG、GA、AA基因型频率分别为85.6%、11.3%和3.1%,其中G和A等位基因频率分别为91.2%和8.8%。正常对照组中,TNF-α基因G/A多态GG、GA、AA基因型频率分别为91.8%、5.5%和2.7%,其中G和A等位基因频率分别为94.5%和5.5%。IgA肾病患者组与正常对照组比较,基因型频率差异有显著性（χ^2=27.2,P〈0.05）,等位基因频率之间差异无显著性（χ^2=0.659,P〉0.05）。结论：TNF-α-308位点基因多态性与内蒙古包头地区汉族人群IgA肾病的发病有相关性,等位基因频率之间差异无显著性（χ^2=0.659,P〉0.05）。     

利用噬菌体随机15肽库确定SLE相关多肽的研究

目的 利用噬菌体随机15肽库确定SLE相关多肽。方法 从系统性红斑狼疮（SLE）病人血清中纯化抗dsDNA多克隆抗体,以此为筛选配基,对噬菌体随15肽库进行亲和筛选。结果 经3轮筛选,每轮的投入／产出比逐轮升高,提示筛选具有良好的富集效果。第3轮筛选后选其中18个克隆重进行结合试验,结果显示有6个公与SLE病人血清反应而不与正常人血反应,经DNA序列测定,发现其中5个克隆相同,通过该序列推出插入的外源短肽序列,合成并纯化该肽段。用此肽段分别与20例SLE病人及20例正常人血清反应,结果差异有显著性。结论 该肽段可能是与SLE相关的抗原多肽。     

血浆同型半胱氨酸和血清叶酸、维生素B12检测及其在糖尿病肾病中的临床意义

应用荧光偏振免疫分析法和时间分辨荧光免疫分析法分别测定血浆同型半胱氨酸(homocysteine,Hcy)和血清叶酸(FA)、维生素B12(VitB12)的水平,探讨其在糖尿病肾病(diabetic nephropathy,DN)中的临床价值。选择137例糖尿病(DM)患者,并根据尿微量白蛋白(uMA)的排泄率及血肌酐(SCr)水平将其分为糖尿病无肾病组、DN初期组、临床DN组和氮质血症组,同时测定以40名健康人作对照组,检测其Hcy、FA和VitB12。采用SPSS10.0统计软件,进行直线回归相关分析。结果显示:四组DM患者血浆Hcy水平分别与对照组比较均显著性增高(P<0.05~0.01),并随DN患者肾脏损伤程度的加重而升高,每两组间相比有显著性差异(P<0.01)。四组DM患者血清FA、VitB12水平分别与对照组比较,除糖尿病无肾病组无显著性差异(P>0.05)外,其余三组均有显著性差异(P<0.01),每两组间比较均有显著性差异(P<0.01)并与血浆Hcy水平呈现负相关。结论:高Hcy血症是DM和DN患者的危险因素,血浆Hcy水平可作为DM和DN病情监测的有效指标,FA、VitB12的降低可能是诱发高Hcy血症的一个重要因素。     

褪黑素对系统性红斑狼疮样小鼠的影响

为了观察褪黑素 (MT )对CJ S13 1所致的SLE样小鼠改变的影响并探讨其作用机制。采用空肠弯曲菌CJ S13 1和CFA混合免疫动物 ,诱导SLE样小鼠改变。结果表明MT 0 0 1、 0 10、 1 0mg/kg/d× 2 8d ,ig能部分或完全拮抗血清抗ssDNA和组蛋白IgG型自身抗体水平的升高 ,抑制ConA及LPS诱导的淋巴细胞增殖反应的增强 ,降低动物尿蛋白水平 ,减轻肾组织病变程度。提示一定剂量的MT对SLE样小鼠改变具有一定的保护作用。