The Serum Cell-Free microRNA Expression Profile in MCTD, SLE, SSc, and RA Patients

Mixed connective tissue disease (MCTD) is a rare disorder characterized by symptoms that overlap two or more Autoimmune Connective Tissue Diseases (ACTDs). The aim of this study was to determine whether miRNAs participating in the TLRs signaling pathway could serve as biomarkers differentiating MCTD or other ACTD entities from a healthy control group and between groups of patients. Although the selected miRNA expression level was not significantly different between MCTD and control, we observed that miR-126 distinguishes MCTD patients from all other ACTD groups. The expression level of miRNAs was significantly higher in the serum of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients compared to controls. The miR-145 and -181a levels distinguished RA from other ACDT patients. miR-155 was specific for SLE patients. MiR-132, miR-143, and miR-29a distinguished RA and SLE patients from the systemic sclerosis (SSc) group. Additionally, some clinical parameters were significantly related to the miRNA expression profile in the SLE group. SLE and RA are characterized by a specific serum expression profile of the microRNAs associated with the Toll-like receptors (TLRs) signaling pathway. The analysis showed that their level distinguishes these groups from the control and from other ACTD patients. The present study did not reveal a good biomarker for MCTD patients.

Download Full-text

Abstract WP319: miRNA Screening of Natural Killer Cell Identifies miR-1224 as a Post-Transcriptional Regulator of NK Cell Function After Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.wp319 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Yan Feng ◽

Hui Zhao ◽

Fu-Dong Shi ◽

Weina Jin

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Nk Cells ◽

Expression Profile ◽

Mirna Expression ◽

Cell Function ◽

Nk Cell ◽

Killer Cell ◽

Mirna Expression Profile ◽

Control Group

Objectives: To screen miRNA profile of peripheral NK cells in ischemic stroke mouse model and investigate a most promising candidate (miR-1224) for post-transcriptional regulation of NK cell function after ischemic stroke. Methods: Mice were subjected to a 60 min focal cerebral ischemia produced by transient intraluminal occlusion of MCAO. For NK cell isolation, cell suspensions from the spleens after reperfusion were enriched for NK cells using magnetic-bead sorting system after staining with anti-NK1.1 microbeads. The nCounter Mouse miRNA array was used to analyze miRNA expression profile in splenic NK cells over the time course of experimental ischemic stroke. Based on the miRNA data, we further in vitro modulated miR-1224 in NK cells using mimics or inhibitor, then injected i.v into Rag2-/-γc-/- recipient mice. Neurological function score was compared and spontaneous infection was assessed by pulmonary bacteria colony culture, and changes in potential signaling pathway (SP1/TNF-α) were verified by rt-PCR and western blot. Results: Through miRNA expression profile analysis, we have identified significant changes at each time point in peripheral NK cells after cerebral ischemia. Among all screened miRNA, miR-1224 remarkably increased in MCAO group, which was verified by PCR. Then isolated NK cells treated with mimics or inhibitors, were transferred to Rag2-/-γc-/- recipient mice. Compared with WT mice, Rag2-/-γc-/- mice with miR-1224 inhibitor exhibited increased NK cell number, enhanced NK cell activation/cytotoxicity feature, as well as better neurological behaviors and reduced pulmonary infection after MCAO. Moreover, compared with the control group, NK cells with miR-1224 inhibitor showed significantly increased SP1 gene and protein phosphorylation. As SP1 gene is one of the potential targets of miR-1224, this study suggests that miR-1224 may regulate NK cell function after MCAO, which is associated with SP1 pathway. Conclusion: The miRNA profiling of splenic NK cells provided insight into the functional mechanism and signaling pathways underlying the distinct organ-specific NK cell properties, which will contribute to the better understanding of NK cell mediated immune-response in relation to different stages of stroke.

Download Full-text

Serum KL-6 as predictive and prognostic marker of interstitial lung disease in childhood connective tissue diseases: a pilot study

Reumatismo ◽

10.4081/reumatismo.2021.1399 ◽

2021 ◽

Vol 73 (3) ◽

Author(s):

R. El-Beheidy ◽

A.M. Domouky ◽

H. Zidan ◽

Y.A. Amer

Keyword(s):

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Lupus Erythematosus ◽

Connective Tissue Diseases ◽

Control Group ◽

Connective Tissue Disorders ◽

Juvenile Systemic Lupus Erythematosus ◽

Median Serum ◽

Juvenile Systemic Sclerosis

This study was aimed to evaluate serum KL-6 levels to determine if this marker can be used for diagnosing and assessing severity of interstitial lung disease (ILD) in children with connective tissue disorders. In total, 40 patients [18 patients with juvenile systemic lupus erythematosus (JSLE), 10 patients with juvenile idiopathic arthritis (JIA), 8 patients with juvenile mixed connective tissue disease (JMCTD), 3 patients with juvenile systemic sclerosis (JSSc), and 1 patient with juvenile dermatomyositis (JDM)] and 20 healthy controls were included in this study. Age, sex, and duration of CTD and ILD (if any) were recorded. Blood samples from all the patients and controls were examined by ELISA. 20 of the 40 patients with CTD (50%) had ILD, 12 were mild and 8 were severe as assessed by spirometry. The median serum KL-6 level was 102.7 U/mL (76.1-180.8) in the CTD with severe ILD group, 72.2 U/mL (58.4- 100.5) in the CTD with mild ILD group, 56.7 U/mL (35.8-68.5) in the CTD without ILD group, and 52.3 U/mL (32.8-62.4) in the control group. KL-6 levels were significantly higher in the CTD with ILD (p<0.05), at a cutoff of 63.4 U/ml identified by ROC curve, serum KL-6 showed a sensitivity of 95.2% and specificity of 89.7%. KL-6 is a valuable biomarker for diagnostic purposes and to detect severity in ILD in childhood CTD.

Download Full-text

Functional state of peripheral and microcirculatory blood flow in patients with pulmonary hypertension on the background of systemic connective tissue diseases

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2019-18-4-11-18 ◽

2019 ◽

Vol 18 (4) ◽

pp. 11-18

Author(s):

E. V. Dolgova ◽

A. A. Fedorovich ◽

T. V. Martynyuk ◽

A. N. Rogoza ◽

I. Ye. Chazova

Keyword(s):

Blood Flow ◽

Pulmonary Hypertension ◽

Connective Tissue ◽

Functional State ◽

Lupus Erythematosus ◽

Connective Tissue Diseases ◽

Functional Class ◽

Control Group ◽

Microcirculatory Blood Flow ◽

Doppler Flowmetry

Aim. To study the functional state of peripheral and microcirculatory blood flow in patients with pulmonary hypertension associated with systemic connective tissue diseases (PH-SCTD).Material and methods. The study included 22 patients (50,1±14,7) with PH-SCTD I–III functional class. 18 patients had systemic scleroderma, 3 – systemic lupus erythematosus, and 1 patient suffered from rheumatoid arthritis. The control group (CG) comprised 25 healthy volunteers (39,3±10). The studies were performed using finger photoplethysmography (FPG), laser Doppler flowmetry (LDF), and capillaroscopy (CS).Results. According to the FPG data, patients with PH-SCTD relative to CG have lower values of occlusion index in the amplitude of 1,51±0,37 and 2,28±0,46 respectively (<0.05). According to LDF data, signs of venular plethora are observed in patients with PH-SCTD, which is manifested by an increase in the amplitude of respiratory-induced fluctuations in blood flow to 0,17±0,11 (PU) versus 0,13±0,07 (PU) in CG (<0.05), an increase in the constrictor reaction in the cold test was 56,4±16,8 % and 42,1±17,9 % (<0.05) and a venous occlusion test was 56,8±18,7 % and 45,2±17,9 % (<0.05), respectively. According to CS data, patients with PH-SCTD have a noticeable increase in the degree of hydration of the interstitial space, which manifests itself in an increase in the size of the pericapillary space to 160,8±37,3 μm against 114,1±17,4 μm in the CG (<0.00001).Conclusions. In patients with PH-SCTD, all regulatory mechanisms and structural components of microvessels, including endothelial and smooth muscle cells, are involved in the pathological process, which is manifested by an increase in the constrictor activity for all types of stimuli and a violation of the filtration-reabsorption mechanism of metabolism.

Download Full-text

Changes in the MicroRNA Profile of the Mandible of Ovariectomized Mice

Cellular Physiology and Biochemistry ◽

10.1159/000443074 ◽

2016 ◽

Vol 38 (4) ◽

pp. 1267-1287 ◽

Cited By ~ 10

Author(s):

LingYu Hao ◽

Jia Li ◽

YaWen Tian ◽

JunHua Wu

Keyword(s):

Signaling Pathway ◽

Complex Network ◽

Expression Profile ◽

Mirna Expression ◽

Mirna Expression Profile ◽

Mineral Density ◽

Ovariectomized Mice ◽

Increased Risk ◽

Public Data ◽

Potential Biomarkers

Background/Aims: In postmenopausal women, a decrease in bone mineral density (BMD) at the hip and spine is associated with an increased risk of tooth loss, possibly caused by the loss of the alveolar bone. The present study explored the effect of the ovariectomy (OVX) of mice on the miRNA expression profile of their bones. Methods: Micro-CT and histological analysis were performed on mice following OVX or sham-operation using the right mandibles. The left mandibles were used for microarray and quantitative RT-PCR to explore the change in their miRNA expression profile. The differentially expressed miRNAs (DEmiRs) of the OVX and sham-operated mice were analyzed by constructing the miRNA-mRNA-function complex network. We then also analyzed the different roles of the regulation of miRNAs in the mandible and femur by combining public data from GEO. Results: OVX could lead to a significant decrease in the BMD in the mandible. A total of 53 DEmiRs including, 18 up-regulated and 35 down-regulated miRNAs, were identified. The analysis of the miRNA-mRNA-pathway complex network suggested that miR-17-5p and miRNA-297a-5p were potential biomarkers in the development of mandibles of OVX mice. A comparison of the analysis data on the mandible and femur showed that the transforming growth factor-β signaling pathway was specifically regulated in the mandible, whereas the Wnt signaling pathway was specifically regulated in the femur. Moreover, miR-17-5p and miR-133a-3p showed different expression tendencies in the mandible and in the femur after OVX. Conclusion: This study provides an integrated function analysis of miRNA in mandibles after OVX and of miR-17-5p and miR-133a-3p as potential biomarkers. Moreover, the mechanism in mandibles may not be comparable with that in femurs with estrogen deficiency.

Download Full-text

Faculty Opinions recommendation of A TARBP2-dependent miRNA expression profile underlies cancer stem cell properties and provides candidate therapeutic reagents in Ewing sarcoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717347979.792703030 ◽

2012 ◽

Author(s):

Stephen Lessnick

Keyword(s):

Stem Cell ◽

Cancer Stem Cell ◽

Expression Profile ◽

Ewing Sarcoma ◽

Mirna Expression ◽

Mirna Expression Profile

Download Full-text

Analysis of the miRNA expression profile in an Aedes albopictus cell line in response to bluetongue virus infection

Infection Genetics and Evolution ◽

10.1016/j.meegid.2016.01.012 ◽

2016 ◽

Vol 39 ◽

pp. 74-84 ◽

Cited By ~ 15

Author(s):

Shanshan Xing ◽

Junzheng Du ◽

Shandian Gao ◽

Zhancheng Tian ◽

Yadong Zheng ◽

...

Keyword(s):

Virus Infection ◽

Cell Line ◽

Aedes Albopictus ◽

Expression Profile ◽

Mirna Expression ◽

Bluetongue Virus ◽

Mirna Expression Profile ◽

Albopictus Cell

Download Full-text

AB0815 FIRST DEGREE RELATIVES OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS - CLINICAL, SEROLOGICAL AND IMMUNOLOGICAL CORRELATIONS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.511 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1432.2-1432

Author(s):

B. Penev ◽

G. Vasilev ◽

D. Kyurkchiev ◽

S. Monov

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Current Knowledge ◽

Statistical Significance ◽

Clinical Signs ◽

Connective Tissue Diseases ◽

Pharmaceutical Products ◽

Systemic Lupus

Background:Antinuclear antibodies (ANA) have been unequivocally recognized as essential for diagnosis and play both pathogenic and diagnostic roles in systemic lupus erythematosus (SLE). SLE and ANA have also been found to be more often among relatives of SLE patients. ANA and other immunological changes are known to appear prior to the clinical onset of the disease and thus can be used as predictors. Studies have reported that relatives of SLE patients who later transitioned to SLE displayed more lupus-associated autoantibody specificities and had early clinical signs. They also displayed elevated baseline plasma levels of inflammatory mediators, including B-lymphocyte stimulator (BLyS) and interferon-associated chemokines, with concurrent decreases in levels of regulatory mediators, e.g. tumor growth factor (TGF)-β. Commonly recognized risk factors for SLE are signs of past Epstein-Barr (EBV) infection, use of estrogen drugs and current smoking. It seems that ANA, immunologic changes and risk factors have not been investigated together in relatives of SLE patients.Objectives:The aim of the study was to determine the relative prevalence of clinical signs of SLE or connective tissue disease (CTD), smoking, use of estrogen drugs and levels of circulating ANA, BLyS, IFN-α, TGF-β, anti-EBV viral capsid antigen (VCA) IgM and IgG antibodies among sera of FDR, non-FDR healthy individuals and SLE patients.Methods:Forty three FDRs of SLE patients were studied along with 15 SLE patients and 15 clinically healthy subjects as control groups. The FDRs and the healthy answered a questionnaire about early clinical signs of CTD, smoking and estrogen use history. The questionnaire was developed based on the existing Screening Questionnaire for Connective Tissue Diseases and current knowledge of most early signs of CTD. Blood samples were obtained and tested for ANA, both by indirect immunofluorescence and immunoblot, anti-dsDNA by ELISA. ELISA was also performed to measure levels of BLys, IFN-α, TGF-β, anti-EBV IgM and IgG.Results:More than half of the FDRs displayed ANA in titer 1:160 or more, with predominately AC-4 type of fluorescence according to International Classification on ANA Patterns (ICAP) compared to only AC-1 and AC-0 among patients and controls respectively. A correlation between the ANA titer and the number of complaints was found. This was particularly valid or reported skin complaints and oral ulcers which appeared more frequently when ANA was 1:320 or above (p=0,018 and 0,038 respectively). Furthermore, oral ulcerations showed positive correlation with the presence of anti-Ro60. No associations were found in the healthy group between reported complaints and ANA titers. Smoking and estrogen use did not differ across the three groups. Patients showed significant differences in levels of BLys (p=0,027), TGF-β (p=0,019) and anti-EBV IgG (p=0.041) compared to both FDRs and controls. Without reaching statistical significance, levels of TGF-β tend to split the FDR group into “healthy-like” and “SLE-like”.Conclusion:Our results show that FDR ANA levels are between those of SLE patients and healthy subject groups. This is consistent with previous studies. The data also suggest that ANA positivity correlates with reported complaints, some of which could be interpreted as very early clinical signs of SLE. Of note, anti-Ro60 is known to be among the earliest ANA that appear in “future” SLE patients and in this study they are related to oral complaints that could be caused by early sicca phenomena. Immunologically, our data support previous findings [1] that the FDRs are a heterogenic group with different “lupus-developing” potential.References:[1]Munroe МE. et al, Soluble Mediators and Clinical Features Discern Risk of Transitioning to Classified Disease in Relatives of Systemic Lupus Erythematosus Patients, Arthritis Rheumatol. 2017 March; 69(3): 630–642.Disclosure of Interests:Bogdan Penev: None declared, Georgi Vasilev: None declared, Dobroslav Kyurkchiev: None declared, Simeon Monov Speakers bureau: I have been paid for giving lectures on statistical data on efficacy of many pharmaceutical products on various companies

Download Full-text

Clinical profile of cutaneous manifestations of connective tissue diseases in North-East India

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20213347 ◽

2021 ◽

Vol 7 (5) ◽

pp. 702

Author(s):

Deepa Mala Subba ◽

Nandakishore Thokchom ◽

Linda Kongbam ◽

Erika Salam ◽

Deepa Yumnam

Keyword(s):

Connective Tissue ◽

Lupus Erythematosus ◽

Cutaneous Lupus Erythematosus ◽

Connective Tissue Diseases ◽

Skin Lesions ◽

Discoid Lupus Erythematosus ◽

Serological Tests ◽

Cross Sectional ◽

Cutaneous Manifestations ◽

North East

Background: Connective tissue diseases (CTDs) are a heterogeneous group of autoimmune disorders having overlapping clinical features. Skin is often involved and it may be the earliest sign of the disease. This study highlighted the various cutaneous manifestations of common CTDs.Methods: A hospital-based cross-sectional study was carried out for a period of two years in 83 patients with CTDs in dermatology OPD, RIMS, Imphal. Detailed history taking, examination and relevant serological tests were performed.Results: The mean age was 39.78±17.29 years with female to male ratio of 4.5:1. Majority of the patients had lupus erythematosus (LE) (N=45) followed by systemic sclerosis (SSc) (N=25), rheumatoid arthritis (RA) (N=6), mixed connective tissue disease (MCTD) (N=4) and morphea (N=3). The most common presentation was raised skin lesions (45.8%) followed by Raynaud’s phenomenon (36.1%), photosensitivity (27.7%), skin tightness (26.5%) and joint pain (19.3%). Among LE patients, chronic cutaneous lupus erythematosus (CCLE) was the commonest variant and localised discoid lupus erythematosus (DLE) (22.9%) was the commonest presentation followed by malar rash and annular subacute lupus erythematosus (SCLE). Skin induration, microstomia and sclerodactyly were seen in most patients of SSc. Antinuclear antibodies were positive in 89.1% of patients. Anti-dsDNA and anti-Sm antibodies were positive in 62.2% and 33.3% of LE patients, anti-Scl 70 antibody was positive in 68% of SSc patients.Conclusions: CTDs are rare but potentially life-threatening. Proper understanding of the spectrum of cutaneous manifestations of CTDs is therefore necessary for early diagnosis and efficient management.

Download Full-text