scholarly journals AB0514 The relationship between serum level of c-terminal telopeptide of type i collagen with course of systemic lupus erythematosus and structural and functional state of bone tissue

2017 ◽  
Author(s):  
S Shevchuk ◽  
L Denyschych ◽  
L Marynych
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Serum Level ◽  
Bone Tissue ◽  
Functional State ◽  
Lupus Erythematosus ◽  
Type I Collagen ◽  
Type I ◽  
Systemic Lupus ◽  
The Relationship

scholarly journals Levels of C-terminal propeptide of type I procollagen and oxyproline in patients with systemic lupus erythematosus: The relationship between the course of the disease and the structural and functional state of bone tissue

2017 ◽  
Vol 8 (2) ◽  
pp. 105-110
Author(s):  
S V. Shevchuk ◽  
L. P. Denyschych ◽  
L. I. Marynych
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Bone Resorption ◽  
Bone Metabolism ◽  
Bone Tissue ◽  
Lupus Erythematosus ◽  
Control Group ◽  
Type I ◽  
Systemic Lupus ◽  
X Ray ◽  
Type I Procollagen

The high prevalence of osteoporosis in patients with systemic lupus erythematosus (SLE) makes it necessary to study the abnormalities in bone metabolism, its relationship with reduced bone mineral density (BMD) and the impact of the disease on it. The aim of this study was to determine serum levels of C-terminal propeptide of type I procollagen (PICP) and oxyproline in patients with SLE, their comparison with the structural and functional state of the patients’ bone tissue and the course of the disease. We examined 58 female SLE patients. The mean age of the patients was 45.1 ± 1.0 years. The control group included 29 healthy individuals,corresponding in age and sex with the researched group. For every patient, data were recorded on age, body mass index (BMI), menstrual history, smoking, chronic SLE damage (SLICC/ACR DI) and disease activity score (SLEDAI), cumulative glucocorticoid dose, serum concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP), bone formation marker (C-terminal propeptide of type I procollagen) and bone resorption marker (oxyproline). In all patients BMD was measured by DXA (Dual-energy X-ray absorptiometry) at two sites. To determine vertebral compression fractures, female SLE patients were examined with an x-ray of the thoracic and lumbar spine. We established that bone turnover markers showed a significant difference between the SLE patients and the control group, with lower levels of PICP and higher levels of oxyproline in the SLE patients. Alterations of bone metabolism were associated with the severity of the disease, active inflammation (high levels of CRP and IL-6), the age of the patients, and the high cumulative glucocorticoid dose but no correlation was found with disease duration, BMI and smoking. Patients with osteopenia, osteoporosis and fractures were significantly more frequently found among patients with reduced bone formation and increased bone resorption rate. Thus, our findings showed that female SLE patients have alterations of bone metabolism in the form of increasing serum oxyproline and reducing serum C-terminal propeptide of type I procollagen, the correction of which would slow the progression of adverse structural and functional changes in the bone tissue. 

scholarly journals Vitamin D in active systemic lupus erythematosus and lupus nephritis: a forgotten player

2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Marwa K. Khairallah ◽  
Yasmine S. Makarem ◽  
Marwa A. Dahpy
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vitamin D ◽  
Serum Level ◽  
Lupus Nephritis ◽  
Negative Correlation ◽  
Lupus Erythematosus ◽  
Significant Negative Correlation ◽  
Systemic Lupus ◽  
Malar Rash ◽  
The Relationship

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with immunological abnormalities (Aringer et al., Arthritis Rheumatol 71:1400-1412, 2019). Vitamin D (VD) has an important role in SLE pathogenesis, as it controls cell cycle progression besides its anti-proliferative effects (Liu et al., J Cell Commun Signal 71, 2019). Determining the relationship between VD with SLE activity and lupus nephritis (LN) can establish a new role for VD in SLE management (Liu et al., J Cell Commun Signal 71, 2019). In our study, we aimed to assess the relationship between levels of VD in patients with SLE activity and with LN and to verify the relationship between VD levels with clinical and laboratory parameters in those patients, in order to assess the validity of adding serum VD level in the routine follow-up as a marker that may lead to earlier diagnosis of SLE activity and LN in adult SLE patients. Results Serum VD was significantly lower in SLE patients (3.38 ± 2.55 ng/ml) versus healthy controls (5.36 ± 2.88 ng/ml) (P < 0.002). Interestingly, serum VD was significantly lower in patient with active SLE according to SLEDAI (3.00 ± 2.27 ng/ml) versus those with inactive SLE (5.10 ± 3.19 ng/ml) (P < 0.02). Significant negative correlation was found between serum level of VD and each of mucocutaneous, malar rash, and renal manifestations. Significant negative correlation was also noticed among SLEDAI (P value = 0.01) and renal SLEDAI scores (P value = 0.021) with serum level of VD. Conclusion Low levels of VD were found to be frequent in SLE patients especially during phases of SLE activity and nephritis. Potent markers of low serum VD level in SLE patients were found to be mucocutaneous, malar rash, and LN. Our results support that VD levels could act as independent risk factors for activity and LN in SLE patients; moreover, treatment with VD supplementation could decrease the incidence of activity and nephritis in SLE patients.

The Relationship Between Systemic Lupus Erythematosus Activity and Persistent Positive Antiphospholipid Antibodies

2018 ◽  
Vol 14 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Zhaleh Shariati Sarabi ◽  
Maryam Sahebari ◽  
Ali Etemad Rezaie ◽  
Mohammad Taghi Norouzi ◽  
Kamila Hashemzadeh ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Systemic Lupus ◽  
Systemic Lupus Erythematosus Activity ◽  
The Relationship

Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus

Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Endothelial Injury ◽  
Control Group ◽  
Systemic Lupus ◽  
Low Concentrations ◽  
The Relationship

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

scholarly journals OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

scholarly journals Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Norzawani Buang ◽  
Lunnathaya Tapeng ◽  
Victor Gray ◽  
Alessandro Sardini ◽  
Chad Whilding ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
Mitochondrial Abnormalities

AbstractThe majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these ‘SLE-like’ conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.

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