Diffusion changes in patients with systemic lupus erythematosus

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disease in which almost all the organs are involved. Neuropsychiatric SLE is of one of the major concerns in the clinical evaluation of this disease. Routine magnetic resonance imaging (MRI) findings are often nonspecific or negative. In this study, we explored the use of diffusion tensor imaging in assisting with the diagnosis of SLE. METHODS: Data from 34 SLE patients (age range, 18-73 years) and 29 age-matched volunteers (age range, 29-64 years) were analyzed. MRI was performed on a 1.5-T clinical MR scanner with a quadrature head coil. The average diffusion constant (D(av)) and diffusion anisotropy maps [fractional anisotropy (FA)] were determined on a pixel-by-pixel basis. Regional diffusion measurements were made by region of interest in the genu and splenium of the corpus callosum (CC), anterior and posterior limb of the internal capsule (IC) and frontal lobe and thalamus. The diffusion distribution was fitted to a triple-Gaussian model. The mean of the brain tissue distribution was determined as a mean diffusion constant for the whole brain (BD(av)). Student's t test was used to determine the diffusion difference between SLE patients and control subjects. The SLE patients were separated into two groups according to their MRI results. A P value lower than .05 was considered to be statistically significant. RESULTS: Twenty of the 34 SLE patients with abnormal MRI results showed findings dominated by nonspecific white matter disease. The BD(av) and D(av) values of the frontal lobe, splenium CC and anterior IC were significantly higher in all SLE patients as compared with the control subjects. The SLE patients with normal MRI results also showed higher BD(av) and D(av) values in the frontal lobe, splenium and anterior and posterior limbs of the IC as compared with the control subjects. There was no significant difference in the D(av) values of the thalamus between the SLE patients and the control subjects. The BD(av) value in the SLE patient group was robustly correlated with the D(av) values of the frontal lobe, splenium and thalamus. These correlations were found to be similarly significant for the SLE patients with normal MRI findings. The diffusion anisotropy measurements showed that splenium CC had the highest FA value in both the control subjects and SLE patients. Overall, SLE patients had lower FA values in the genu and splenium CC as compared with the control subjects. In the group of patients with normal MRI findings, the FA values of the genu and splenium CC as well as the anterior IC were also lower than those in the control subjects. Pearson's correlation statistics revealed robust correlations between the measurements of D(av) and FA values in the SLE patient group. CONCLUSION: Quantitative diffusion imaging and diffusion anisotropy showed early changes in the brains of the SLE patients. Increased BD(av) and D(av) values of the frontal lobe as well as decreased anisotropy in the genu CC and anterior IC may represent preclinical signs of central nervous system involvement of SLE even when the routine MRI findings are negative or nonspecific. Quantitative diffusion analysis may prove to be useful in detecting the initial brain involvement of SLE and may enable monitoring of early disease progression and treatment efficacy.     

初发系统性红斑狼疮患者外周血清IL-17的表达

目的探讨IL-17在初发系统性红斑狼疮（SLE）患者外周血清中的表达水平及其临床意义。方法选择42例初次诊断、未经治疗的SLE患者（SLE组）及26例同期健康志愿者（对照组）,采用双抗体夹心酶联免疫吸附试验（ELISA）方法测定外周血清IL-17水平,同时检测外周血抗ds- DNA等抗体及免疫球蛋白、补体等水平并进行相关分析。结果活动期和缓解期SLE患者血清IL-17水平均较对照组明显升高,差异均有统计学意义（均P＜0.05）。活动期和缓解期SLE患者间血清IL-17水平的差异无统计学意义（P＞0.05）。具有皮肤损害的SLE患者血清IL-17水平较无皮肤损害者高,使用环磷酰胺的SLE患者血清IL-17水平较未使用环磷酰胺者高,差异有统计学意义（P＜0.05）。SLE患者血清IL-17水平与SLEDAI、血沉、CRP、IgG、C3、C4均无相关性（均P＞0.05）。19例SLE活动期患者治疗1个月后血清IL-17水平较治疗前明显下降,差异有统计学意义（P＜0.05）。结论 IL-17与狼疮患者的皮肤损害密切相关;IL-17在SLE的发病中起到重要作用并与疾病严重性有关。     

Genome-wide computational analyses of microRNAs and their targets from Canis familiaris

By computational analyses, we identified 357 miRNA candidates from Canis familiaris genome, among which 300 are homology of characterized human miRNAs, the remains are not reported in any other animal. Of the 357 miRNA genes, 142 are organized into 53 clusters, and two clusters locate in the paternally imprinted region. These dog miRNAs may regulate more than 800 possible targets, which are involved in a wide range of cellular processes. Remarkably, miR-186 resides in the eighth intron of its target gene in the same orientation, suggesting a feedback regulation of miRNA on its host gene.     

Quartz crystal microbalance immunosensor for the detection of antibodies to double-stranded DNA

We report the development of a novel quartz crystal microbalance immunosensor with the simultaneous measurement of resonance frequency and motional resistance for the detection of antibodies to double-stranded DNA (dsDNA). The immobilization of poly(l-lysine) and subsequent complexation with DNA resulted in formation of a sensitive dsDNA-containing nanofilm on the surface of a gold electrode. Atomic force microscopy has been applied for the characterization of a poly(l-lysine)–DNA film. After the blocking with bovine serum albumin, the immunosensor in flow-injection mode was used to detect the antibodies to dsDNA in purified protein solutions of antibodies to dsDNA and to single-stranded DNA, monoclonal human immunoglobulin G, DNase I and in blood serum of patients with bronchial asthma and systemic lupus erythematosus. Experimental results indicate high sensitivity and selectivity of the immunosensor. In memoriam Prof. Victor G. Vinter     

Polymorphisms of COTL1 gene identified by proteomic approach and their association with autoimmune disorders

To select candidate genes, we attempted to comparative analysis of protein levels between rheumatoid arthritis (RA) patients and healthy controls by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). We identified 17 proteins that showed up- or down-regulated spots in RA patients. We found that coactosin-like1 (COTL1) were highly expressed in RA patients compared with healthy controls. We performed a case-control study to determine whether the COTL1 gene polymorphisms were associated with RA and systemic lupus erythematosus (SLE). The genotype frequency of c.-1124G>T and the allelic frequency of c.484G>A in RA patients, and the genotype frequency of c.484G>A in SLE patients were significantly different from healthy controls (P = 0.009, 0.027, and 0.025, respectively). We also investigated the correlation with the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody in RA patients, and anti-nuclear antibodies (ANA) in SLE patients. The c.484G>A polymorphism in RA patients has significant association with the levels of anti-CCP antibody (P = 0.03). Our findings demonstrated that c.-1124G>T and c.484G>A polymorphisms of the COTL1 gene might be associated with the genetic susceptibility of autoimmune disorders.     

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.     

化学发光酶联免疫分析测定血清中抗DNA抗体

建立起适于临床应用的抗ＤＮＡ抗体化学发光酶联免疫分析法。该法精密度良好，相对标准偏差为２．４％。比ＥＬＩＳＡ法更加简便、经济、省时，同时提高了灵敏度（８倍）和血清的阳性检出率。探讨了检测系统中对碘苯酚增强鲁米诺－过氧化氢－辣根过氧化物酶化学发光反应机理。     

血浆循环DNA浓度在原发性干燥综合征和系统性红斑狼疮诊治中的意义

目的比较原发干燥综合征（pSS）、系统性红斑狼疮（SLE）患者外周血浆中循环DNA（cDNA）浓度的差异性，探讨cDNA浓度在pSS、SLE诊治中的意义。方法选用人类基因组管家基因甘油醛-3-磷酸脱氢酶（GAPDH）设计引物，测定pSS、SLE及健康对照组中血浆cDNA浓度，同时测定血沉（ESR）、C-反应蛋白（CRP）、免疫球蛋白（IgA、IgG、IgM）并评定不同疾病的活动指数和损害指数，分析血浆cDNA浓度与疾病活动性、相关参数的关系。结果 pSS组cDNA浓度[（368.24±196.68）ng/ml]明显高于SLE组[（244.51±164.10）ng/ml]及健康对照组[（24.56±16.76）ng/ml]，差异均有统计学意义（均P＜0.05）；pSS组中的cDNA浓度值与干燥综合征活动指数（SSDAI）呈正相关（P＜0.05），与干燥综合征损害指数（SSDDI）无相关性（P＞0.05）；SLE组中cDNA浓度值与SLE活动指数（SLEDAI）无相关性（P＞0.05）。结论 cDNA浓度可作为pSS与SLE鉴别指标之一，pSS患者cDNA浓度与SSDAI呈正相关，可作为pSS疾病活动性观察指标之一。     

基于液相色谱-质谱联用系统的系统性红斑狼疮患者血浆代谢组学分析

应用快速分离液相色谱-串联四极杆飞行时间质谱(RRLC-Q-TOF/MS)系统对系统性红斑狼疮(SLE)患者血浆样本进行代谢指纹图谱的分析。分别应用监督模式识别方法正交信号校正结合偏最小二乘法-判别分析(OSC-PLS-DA)对代谢组数据进行处理,结果显示SLE患者与健康人群对照组的代谢指纹存在明显差异;进一步从SLE患者血清代谢图谱中筛选出10个对分类有显著贡献的离子,定性鉴定出7种代谢标志物,发现SLE患者存在异常的氨基酸、磷脂和卟啉的代谢状态。本研究可为SLE的监测和诊断以及SLE发病的分子基础研究提供科学依据。     

球形纤维素固定化DNA制备免疫吸附剂

以球形纤维素为载体,经环氧氯丙烷活化后共价键联小牛胸腺DNA,制备DNA免疫吸附剂,通过血液灌流能够治疗系统性红斑狼疮.对病人血清的吸附实验结果表明,每毫升吸附剂与3mL病人血清混合,于37℃保温1 h,可吸附除去40%～70%致病抗体