High expression levels of microRNA-629, microRNA-525-5p and microRNA-516a-3p in paediatric systemic lupus erythematosus

Paediatric systemic lupus erythematosus (pSLE) refers to childhood-onset systemic lupus erythematosus. pSLE has its own unique characteristics, and its pathogenesis is unclear. To study the relationship between microRNAs (miRNAs) and pSLE, we selected three pSLE patients who were newly diagnosed and had not yet been treated, and two controls were also included. We collected their peripheral blood mononuclear cells to perform Agilent human miRNA (8?×?15 k) 12.0 analysis. To verify the results, we next selected 12 other pSLE patients who had different disease activities and 3 healthy controls and conducted real-time PCR. The results showed high expression of miRNA-516a-3p, miRNA-629 and miRNA-525-5p in pSLE patients with active disease; these levels were normal in patients without active disease. Increased expression levels of these three miRNAs were positively correlated with the score obtained from the systemic lupus erythematosus disease activity index scoring system (SLEDAI) 2000 and C-reactive protein (CRP) levels. Furthermore, the target genes of these three miRNAs were important to the pathogenesis of pSLE. Therefore, these three miRNAs might be specific to pSLE and may be used as novel biomarkers of pSLE to diagnose and monitor the disease.     

Analysis of microRNA-199a-3p expression in CD4+ T cells of systemic lupus erythematosus

Clinical Rheumatology - Accumulating evidence have suggested microRNAs (miRNAs) play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here we aimed to explore aberrant...     

Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers

Abstract

Systemic lupus erythematosus is a chronic, multisystemic, autoimmune disease that may involve the central, peripheral, and autonomic nervous systems and can present with a wide variety of neurological and psychiatric manifestations. In this article, we review the recent literature pertaining to the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). We searched the PUBMED database with no chronological constraints using the following terms: “neuropsychiatric systemic lupus erythematosus” cross-referenced with the terms “pathogenesis” and “biomarkers” for full-text articles in English. The etiology of NPSLE is as yet unknown, though numerous autoantibodies and cytokines have been suggested as possible mediators. Of the numerous autoantibodies and biomarkers examined, anti-phospholipid, anti-ribosomal P, anti-neuronal, anti-glial fibrillary acidic protein (GFAP), anti-endothelial cell, anti-N-methyl-d-aspartate (NMDA), microtubule-associated protein 2 (MAP-2), and matrix metalloproteinase-9 (MMP-9) appear to be elevated in patients with NPSLE. Cytokines that may be involved in the pathology of NPSLE include interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and interferons (IFN)-α and -γ. With continued advances in immunological research, new insights into the pathophysiologic mechanisms of NPSLE may lead to the development of biomarkers and new treatment strategies.     

Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers

Systemic lupus erythematosus is a chronic, multisystemic, autoimmune disease that may involve the central, peripheral, and autonomic nervous systems and can present with a wide variety of neurological and psychiatric manifestations. In this article, we review the recent literature pertaining to the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). We searched the PUBMED database with no chronological constraints using the following terms: “neuropsychiatric systemic lupus erythematosus” cross-referenced with the terms “pathogenesis” and “biomarkers” for full-text articles in English. The etiology of NPSLE is as yet unknown, though numerous autoantibodies and cytokines have been suggested as possible mediators. Of the numerous autoantibodies and biomarkers examined, anti-phospholipid, anti-ribosomal P, anti-neuronal, anti-glial fibrillary acidic protein (GFAP), anti-endothelial cell, anti-N-methyl-d-aspartate (NMDA), microtubule-associated protein 2 (MAP-2), and matrix metalloproteinase-9 (MMP-9) appear to be elevated in patients with NPSLE. Cytokines that may be involved in the pathology of NPSLE include interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and interferons (IFN)-α and -γ. With continued advances in immunological research, new insights into the pathophysiologic mechanisms of NPSLE may lead to the development of biomarkers and new treatment strategies.     

MicroRNA-126 and 146a as potential biomarkers in systemic lupus erythematosus patients with secondary antiphospholipid syndrome

BackgroundMicroRNAs (miRs) are noncoding gene regulators that may have a role as diagnostic or prognostic biomarkers in systemic lupus erythematosus (SLE) and its complications. SLE is an autoimmune disease that may be associated with secondary antiphospholipid syndrome (APS).Aim of the workTo evaluate the plasma levels of both miR-146a and miR-126 as well as serum alpha interferon (α IFN) in Egyptian SLE patients with and without secondary APS and to investigate their potential role in disease pathogenesis and their utility as biomarkers for APS.Patients and methods88 SLE patients including 30 cases with secondary APS and 40 matched healthy individuals were enrolled in this study. SLE disease activity index (SLEDAI) was assessed. The plasma levels of miR-146a and miR-126 were determined by Realtime polymerase chain reaction (PCR) in all participants.ResultsThe mean age of the patients was 31.3 ± 9.6 years with disease duration 1–17 years. Plasma miR-146a was significantly lower and miR-126 significantly higher in SLE compared to controls. MiR126 was also higher in secondary APS patients compared to patients without. Serum IFN-α ws significantly higher in patients (71.2 ± 19.7 pg/ml) compared to control (43.2 ± 9.7 pg/ml) (p < 0.001). MiR-126 at a cut off of 2.66 can discriminate between SLE patients with and without secondary APS with a sensitivity of 76.67% and specificity of 81.01% ((95% CI 0.685–0.902, P < 0.001).ConclusionCirculating miR-126 could be a potential noninvasive biomarker in SLE associated with secondary APS. Further studies are needed in view of the limited data on the expressions of microRNA in APS.     

Possible novel biomarkers of organ involvement in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by excessive production of various autoantibodies, which play important roles in the pathogenesis of SLE. Apart from classical autoantibodies such as anti-double stranded DNA antibody (anti-dsDNA), anti-Smith antibody (anti-Sm), and anti-phospholipid antibody (APL), recent studies focus on some novel autoantibodies including anti-complement (C) 1q antibody (anti-C1q), which is closely correlated with lupus nephritis; anti-N-methyl-d-asparate receptor antibody (NMDAR), which mediates neuropsychiatric manifestations in SLE to some extent; anti-galectin, which is involved in secondary anti-phospholipid syndrome (APS) in SLE; and anti-Müllerian hormone (AMH), which represents a more specific biomarker for subclinical ovarian damage caused by the disease itself or cytotoxic drugs in SLE patients. Correlation of these autoantibodies with disease activity and organ involvement of SLE may help to evaluate disease severity, efficacy of treatment, and long-term prognosis. Furthermore, combined measurement of a variety of autoantibodies is supposed to be more valuable in estimating disease activity and severity.     

Diagnostic accuracy of miRNAs as potential biomarkers for systemic lupus erythematosus: a meta-analysis

To systematically evaluate the diagnostic accuracy of miRNAs as potential biomarkers for systemic lupus erythematosus (SLE). Studies were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM) disc database, and languages were limited in English and Chinese. QUADAS-2 tool was applied to assess the quality of eligible studies. Random-effect model was applied to calculate pooled effects of miRNAs on diagnosing SLE. Subgroup analysis was used to explore the sources of heterogeneity. All data were calculated and analyzed by Meta-Disc 1.4 and RevMan 5.3 software. Six eligible studies were included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of miRNAs were 0.75(95% CI 0.71–0.79), 0.72(95% CI 0.66–0.78), and 8.79(95% CI 4.91–15.73), respectively. The pooled positive likelihood ratio was 2.71(95% CI 2.20–3.33) and negative likelihood ratio was 0.34(95% CI 0.24–0.48). The area under the curve was 0.787. The subgroup analysis showed that the number of healthy controls might be the sources of heterogeneity. MiRNAs in blood have moderate accuracy and influence on diagnosing SLE, and the exact diagnostic value should be confirmed by further studies.     

Dysregulation of microRNA146a-5p expression in systemic lupus erythematosus females: Diagnostic potential and association with ocular manifestations

BackgroundMicro-ribonucleic acids (miRNA) are key regulators for the expression of related target genes and their aberrant expression has a substantial role across many pathways within autoimmunity.Aim of the workTo evaluate the expression of miRNA-146a-5p in systemic lupus erythematosus (SLE) patients and to assess its relation to the disease activity and various disease parameters with specific focus on the ocular manifestations.Patients and methods42 female SLE patients and 39 matched healthy individuals were enrolled in this study. The serum level of miRNA146a-5p was evaluated by a quantitative real-time polymerase chain reaction (PCR) (Taqman technology).ResultsThe mean age of the patients was 29 ± 9.1 years. The serum level of miRNA146a-5p was significantly higher in SLE cases (3.21 ± 4.47 fold change) compared to the controls (1.54 ± 1.66 fold change) (p = 0.001). A significant negative association was found between the serum level of miRNA146a-5p and C4 level (p = 0.018). Expression levels of miRNA146a-5p were significantly decreased in patients with photosensitivity (p = 0.006). Regarding ocular manifestations, a lower level of miRNA146a-5p was detected in patients suffering from dry eyes, cataract, keratitis and drusen compared to patients without and a higher level was found in those suffering from retinopathy. Serum miRNA146a-5p at a cut off value of 1.36 could discriminate patients from controls (95%CI: 0.61–0.84; p = 0.001) at a sensitivity of 69% and specificity of 64.1%.ConclusionThese findings suggest that miR-146a-5p could be a potential diagnostic biomarker in SLE and may implicate a functional role in the pathophysiology of the ocular manifestations in the disease.     

Atherosclerosis biomarkers in female systemic lupus erythematosus patients with and without cardiovascular diseases

Background

Cardiovascular diseases (CVD) and atherosclerosis are over presented in patients with systemic lupus erythematosus (SLE).

High-mobility group box 1 represents a potential marker of disease activity and novel therapeutic target in systemic lupus erythematosus

High-mobility group box 1 (HMGB1) protein is a nuclear DNA-binding protein, which functions as an alarmin when released from cells. Recent studies implicate extracellular HMGB1 in the pathogenesis of systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by the formation of multiple autoantibodies, especially those directed against nucleosomes and double-stranded (ds)DNA. Elevated concentrations of HMGB1 are observed in sera as well as in skin lesions of patients with lupus. Of importance, serum HMGB1 and anti-HMGB1 autoantibody levels correlate with disease activity. In the blood of patients with SLE, HMGB1 is complexed with nucleosomes, at least partially. Moreover, HMGB1-nucleosome complexes from apoptotic cells activate antigen-presenting cells. Injection of HMGB1-nucleosome complexes into nonautoimmune mice results in the formation of autoantibodies against dsDNA and histones in a Toll-like receptor (TLR) 2-dependent manner. Additionally, HMGB1, as a part of DNA-anti-DNA immune complexes, can interact with receptor for advanced glycation end products (RAGE) on the surface of plasmacytoid dendritic cells and B cells leading to TLR9-dependent interferon (IFN)α release and activation of autoreactive B cells, respectively. HMGB1 attached to neutrophil extracellular traps may contribute to IFNα production by facilitating the recognition of self-nucleic acids. Furthermore, HMGB1, complexed with DNA and pathogenic anti-DNA autoantibodies, activates its receptors, TLR2, TLR4 and RAGE, and may thereby be involved in anti-DNA autoantibody-induced kidney damage in lupus nephritis. Collectively, these findings suggest that HMGB1 is a potential marker of disease activity and, because of its probable involvement in the pathogenesis, a novel therapeutic target in SLE.     

抗核小体抗体检测在系统性红斑狼疮中的临床价值

目的评价抗核小体抗体（ANuA）对系统性红斑狼疮（SLE）的诊断价值。方法检测216例SLE患者和150例非SLE风湿病患者的血清ANuA、抗双链DNA（ds—DNA）抗体、C3、C4、血沉（ESR）水平,评估SLE患者24小时尿蛋白定量及病情活动程度。利用ROC曲线、四格表、多因素秩和检验、多因素相关分析评价ANuA对SLE的诊断价值。结果ANuA诊断SLE的灵敏度和特异度分别为57．4％和98．0％。SLE活动组的ANuA水平明显高于SLE稳定组和非SLE风湿病组;肾脏受累的SLE患者体内的ANuA水平明显高于无肾脏受累者及非SLE风湿病组。ANuA与抗ds—DNA抗体、SLEDAI评分呈正相关,与补体C3、C4呈负相关。结论ANuA对于SLE的诊断价值与抗ds—DNA抗体相似;在中低度活动的SLE患者中其诊断价值明显高于抗ds—DNA抗体;在抗ds—DNA抗体阴性的情况下,ANuA水平的升高有助于SLE诊断的确立;SLE患者体内ANuA水平可作为判断病情活动的指标之一。     

Fatigue and its correlates in Indian patients with systemic lupus erythematosus

Clinical Rheumatology - Fatigue is a disabling yet poorly understood symptom in patients with systemic lupus erythematosus (SLE). Many variables influence fatigue including physical function, pain,...     

Antineutrophil autoantibodies and their target antigens in systemic lupus erythematosus

Various autoantibodies have been identified in sera from patients with systemic lupus erythematosus (SLE) and autoantibodies against neutrophil have been reported. It was suggested that antineutrophil autoantibodies might be involved in the pathogenesis of neutrocytopenia; however, the role of autoantibodies against neutrophil precursors and their specific target autoantigen(s) remained further characterized. The objective was to investigate the target antigens and clinical associations of autoantibodies against neutrophils and neutrophil precursors in patients with SLE. Sera were collected from 92 patients with SLE and renal biopsy proven lupus nephritis. Cell lysates of peripheral neutrophils (as mature neutrophils) from a normal blood donor and white blood cells from a patient with blast crisis of chronic granulocytic leukemia (CGL) (as neutrophil precursors) were used as antigens in Western blot analysis to detect autoantibodies in sera from patients with SLE. The clinical significance of antineutrophil autoantibodies that recognized different antigens were further analysed. Using normal peripheral neutrophils as antigens, two bands could be blotted: 64 kD (33/92, 35.9%) and 50 kD (13/92, 14.1%). The prevalence of anti-64 kD autoantibody in patients with positive rheumatic factor was significantly higher than that in patients without (54.5 versus 18.8%, P < 0.05). Using CGL white cells as antigen, five bands could be blotted: 60 kD (34/92, 37.0%), 50 kD (32/92, 34.8%), 29 kD (27/92, 29.3%), 42 kD (19/92, 20.7%) and 18 kD (16/92, 17.4%). The prevalence of anti-60 kD autoantibody was significantly higher in patients with neutrocytopenia than that in patients without neutrocytopenia (100 versus 48.3%, P < 0.01). The prevalence of anti-29 kD autoantibody was significantly higher in patients with alopecia than that in patients without alopecia (45.8 versus 20.8%, P < 0.05). Furthermore, the prevalences of anti-60 kD, anti-50 kD and anti-42 kD autoantibodies were significantly higher in patients with anti-Ro autoantibody than those in patients without; the prevalences of anti-29 kD and anti-18 kD autoantibodies were significantly higher in patients with anti-Sm autoantibody than those in patients without. We conclude that there are heterogeneous autoantibodies against both neutrophils and their precursors in sera from patients with SLE. Different autoantibodies may have different clinical significance.     

阿尔茨海默病患者血浆microRNA-101a-3p的表达

目的探讨microRNA在阿尔茨海默病(AD)患者血浆中的差异变化,以寻求一个可能作为辅助诊断AD的早期生物标志物。方法实验分为患者组和健康对照组,分别取其血浆并提取microRNA,利用microRNA基因芯片和荧光定量PCR的方法寻找有表达差异的microRNA。结果基因芯片筛选出68个AD相关的差异表达microRNAs基因(P0.05),其中miR-101a的表达水平在AD患者中显著低于对照组(log=-5.53,P=1.19×10-5),选定为感兴趣miRNA;荧光定量PCR示:患者组中miR-101a的相对表达量为8.834×10-4±2.842×10-4,对照组为6.305×10-3±1.161×10-3。患者组表达量仅为对照组14%,两组间差异有统计学意义(F=21.76,P0.001),结果与miRNA芯片检测结果一致。ROC示:如果以0.002 163为诊断临界值,即miR-101a相对表达量低于0.002 163提示诊断AD。结论 miR-101a可能通过多种途径影响AD的发生发展,可能作为一种辅助诊断AD的早期生物标志物。     

Intestinal pseudo-obstruction in patients with systemic lupus erythematosus: A real diagnostic challenge

Intestinal pseudo-obstruction secondary to systemic lupus erythematosus (SLE) is a rare syndrome described in recent decades. There are slightly over 30 published cases in the English language literature, primarily associated with renal and hematological disease activity. Its presentation and evolution are a diagnostic challenge for the clinician. We present four cases of intestinal pseudo-obstruction due to lupus in young Mexican females. One patient had a previous diagnosis of SLE and all presented with a urinary tract infection of varying degrees of severity during their evolution. We consider that recognition of the disease is of vital importance because it allows for establishing appropriate management, leading to a better prognosis and avoiding unnecessary surgery and complications.