Clinical significance of neutrophils functional activity in patients
with systemic lupus erythematosus.

There is a revival of interest to the role of innate immunity in SLE and neutrophils as its main cellular components. Lupus neutrophils are characterized by impaired phagocytic capabilities, enhanced apoptosis and NETosis, an alternative mechanism ofneutrophil cell death, abnormal clearance ofapoptotic bodies and NETosis products. Therefore, investigation ofpathogenetic processes involving neutrophils is of immense importance, it may help in searching for potential therapeutic targets, understanding the mechanisms of drugs action already used in clinical practice and optimizing the therapeutic regimens by developing predictive factors. Free radical production is one of the crucial neutrophil functions. Thus, the study of neutrophil radical-producing function as a component of their functional status seems expedient. To attain this objective, a new method of luminol-enhanced chemiluminescence with a preliminary two-step stimulation by phorbol-12-myristate-13 acetate and formyl-methionyl-leucyl-phenylalanine was developed. Neutrophil radical-producing activity was evaluated in 46 SLE patients compared to 87 healthy controls. Increased spontaneous production of reactive oxygen species and more pronounced response to the PMA and fMLP effects were found. It was shown by higher specific peak and specific integral neutrophil activity, comparing to the control group. Interleukin-lfi for SLE patients’ neutrophils appeared to be both a pronounced stimulus and a priming agent, it was only a weak priming agent in healthy controls. These results are consistent with research data showing increased functional activity of neutrophils in SLE associated with increased production of pro-inflammatory cytokines, as well as increased production of neutrophil extracellular traps in the absence of additional stimulation, which may be a consequence of cytokine-primed condition.

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Low Urine Secretion of Semaphorin3A In Lupus Patients With Proteinuria

10.21203/rs.3.rs-750580/v1 ◽

2021 ◽

Author(s):

Doron Rimar ◽

Merav Lidar ◽

Nasrin Eiza ◽

Adi D Sabag ◽

Elias Toubi ◽

...

Keyword(s):

Immune Responses ◽

Disease Activity ◽

Lupus Erythematosus ◽

Renal Involvement ◽

Control Group ◽

Healthy Controls ◽

Adaptive Immune ◽

Urine Concentrations ◽

Urine Levels

Abstract Background: Immune semaphorins are important players in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to be associated with SLE disease activity. Objectives: To assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Methods: Urine levels of sema3A were analyzed in 38 SLE patients of whom 13 had renal involvement and were compared to 10 healthy controls and 8 RA patients (disease control group). Results: The secretion of urine sema3A was found to be significantly lower in SLE patients compared to healthy controls and RA patients (4.9±3.9 ng/ml, 8.5±2.7 ng/ml, 9.85±1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was significantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0±3.4 ng/ml vs 6.5±3.8 ng/ml, p=0.03). Urine sema3A was inversely correlated with proteinuria and SLE disease activity. Conclusion: Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.

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Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

10.1101/2021.08.15.456375 ◽

2021 ◽

Author(s):

Yiyangzi Ma ◽

Ruru Guo ◽

Yiduo Sun ◽

Xin Li ◽

Lun He ◽

...

Keyword(s):

Gut Microbiota ◽

Lupus Erythematosus ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Healthy Controls ◽

Germ Free ◽

Autoimmune Antibodies ◽

Expression Of Genes ◽

Rdna Sequencing

Background: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. Results: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Conclusions: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

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Abstract MP41: A Role Of Isolevuglandins In Systemic Lupus Erythematosus Associated Autoimmunity And Hypertension

Hypertension ◽

10.1161/hyp.76.suppl_1.mp41 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

David M Patrick ◽

Nestor de la Visitacion ◽

Michelle J Ormseth ◽

Charles Stein ◽

Sean S Davies ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Immune Activation ◽

Lupus Erythematosus ◽

Cell Activation ◽

Immune Cell ◽

Healthy Controls ◽

Systemic Lupus ◽

Immune Cell Activation ◽

Systemic Immune Activation

Essential hypertension and systemic lupus erythematosus (SLE) are devastating conditions that disproportionately affect women. SLE has heterogeneous manifestations and treatment is limited to the use of non-specific global immunosuppression. Importantly, there is an increased prevalence of hypertension in women with SLE compared to healthy controls. Isolevuglandins (IsoLGs) are oxidation products of fatty acids that form as a result of reactive oxygen species. These molecules adduct covalently to lysine residues of proteins. Adducted proteins are then presented as autoantigens to T-cells resulting in immune cell activation. Previous studies have shown an essential role of IsoLGs in immune cell activation and the development of hypertension in animal models. We hypothesize that isoLGs are important for the development of hypertension and systemic immune activation in SLE. We first examined isoLG adduct accumulation within monocytes of human subjects with SLE compared to healthy controls. By flow cytometry, we found marked accumulation of isoLG adducts within CD14 + monocytes (34.2% ± 12.4% vs 3.81% ± 2.1% of CD14 + , N = 10-11, P <0.05). We confirmed this increase in isoLG adducts by mass spectrometry. To determine a causative role of isoLG adducts in immune activation and hypertension in SLE, we employed the B6.SLE123 and NZBWF1 mouse models of SLE. Animals were treated with the isoLG scavenger 2-hydroxybenzylamine (2-HOBA) or vehicle beginning at 7 weeks and were sacrificed at 32 weeks of age. C57BL/6 and NZW were used as controls. Importantly, treatment with 2-HOBA attenuated blood pressure in both mouse models (systolic BP 136.2 ± 5.6 mmHg for B6.SLE123 vs 120.9 ± 4.46 mmHg for B6.SLE123 +2HOBA; 164.7 ± 24.4 mmHg for NZBWF1 vs 136.9 ± 14.9 mmHg for NZBWF1 +2HOBA, N = 6-8, P < 0.05). Moreover, treatment with 2-HOBA reduced albuminuria and renal injury in the B6.SLE123 model (albumin/creatinine ratio 33.8 ± 2.0 x 10 -2 μg/mg for B6.SLE123 vs 5.5 ± 0.9 x 10 -2 μg/mg for B6.SLE123 +2HOBA, N = 7-9, P < 0.05). Finally, immune cell accumulation in primary and secondary lymphoid organs is significantly attenuated by 2-HOBA. These studies suggest a critical role of isoLG adduct accumulation in both systemic immune activation and hypertension in SLE.

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Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

BioMed Research International ◽

10.1155/2020/7828392 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17 ◽

Cited By ~ 6

Author(s):

Wanxin Liu ◽

Ren Zhang ◽

Rong Shu ◽

Jinjing Yu ◽

Huan Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Cancer Susceptibility ◽

Precancerous Lesions ◽

Bacterial Community Composition ◽

Intestinal Flora ◽

Control Group ◽

Healthy Controls ◽

Healthy Individuals

A lot of previous studies have recently reported that the gut microbiota influences the development of colorectal cancer (CRC) in Western countries, but the role of the gut microbiota in Chinese population must be investigated fully. The goal of this study was to determine the role of the gut microbiome in the initiation and development of CRC. We collected fecal samples of 206 Chinese individuals: 59 with polyp (group P), 54 with adenoma (group A), 51 with colorectal cancer (group CC), and 42 healthy controls (group HC).16S ribosomal RNA (rRNA) was used to compare the microbiota community structures among healthy controls, patients with polyp, and those with adenoma or colorectal cancer. Our study proved that intestinal flora, as a specific indicator, showed significant differences in its diversity and composition. Sobs, Chao, and Ace indexes of group CC were significantly lower than those of the healthy control group (CC group: Sobs, Chao, and Ace indexes were 217.3 ± 69, 4265.1 ± 80.7, and 268.6 ± 78.1, respectively; HC group: Sobs, Chao, and Ace indexes were 228.8 ± 44.4, 272.9 ± 58.6, and 271.9 ± 57.2, respectively). When compared with the healthy individuals, the species richness and diversity of intestinal flora in patients with colorectal cancer were significantly reduced: PCA and PCoA both revealed that a significant separation in bacterial community composition between the CC group and HC group (with PCA using the first two principal component scores of PC1 14.73% and PC2 10.34% of the explained variance, respectively; PCoA : PC1 = 14%, PC2 = 9%, PC3 = 6%). Wilcox tests was used to analyze differences between the two groups, it reveals that Firmicutes (P=0.000356), Fusobacteria (P=0.000001), Proteobacteria (P=0.000796), Spirochaetes (P=0.013421), Synergistetes (P=0.005642) were phyla with significantly different distributions between cases and controls. The proportion of microorganism composition is varying at different stages of colon cancer development: Bacteroidetes (52.14%) and Firmicutes (35.88%) were enriched in the healthy individuals; on the phylum level, the abundance of Bacteroidetes (52.14%-53.92%-52.46%–47.06%) and Firmicutes (35.88%-29.73%-24.27%–25.36%) is decreasing with the development of health-polyp-adenomas-CRC, and the abundance of Proteobacteria (9.33%-12.31%-16.51%–22.37%) is increasing. PCA and PCOA analysis showed there was no significant (P<0.05) difference in species similarity between precancerous and carcinogenic states. However, the composition of the microflora in patients with precancerous lesions (including patients with adenoma and polyp) was proved to have no significant disparity (P<0.05). Our study provides insights into new angles to dig out potential biomarkers in diagnosis and treatment of colorectal cancer and to provide scientific advice for a healthy lifestyle for the sake of gut microbiota.

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Staphylococcus aureus Infection Induced Oxidative Imbalance in Neutrophils: Possible Protective Role of Nanoconjugated Vancomycin

ISRN Pharmacology ◽

10.5402/2012/435214 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Subhankari Prasad Chakraborty ◽

Panchanan Pramanik ◽

Somenath Roy

Keyword(s):

Oxidative Stress ◽

Staphylococcus Aureus ◽

Cell Damage ◽

Treated Group ◽

Protective Role ◽

Control Group ◽

Similar Dose ◽

Cellular Components

Staphylococcus aureus infection causes oxidative stress in neutrophils. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was aimed to test the protective role of nanoconjugated vancomycin against vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection induced oxidative stress in neutrophils. VSSA- and VRSA-infection were developed in Swiss mice by intraperitoneal injection of 5×106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was treated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, and nitrite generation and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative imbalance in neutrophils.

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Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients

Mediators of Inflammation ◽

10.1155/2014/385297 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 43

Author(s):

Vinod Umare ◽

Vandana Pradhan ◽

Milind Nadkar ◽

Anjali Rajadhyaksha ◽

Manisha Patwardhan ◽

...

Keyword(s):

Proinflammatory Cytokines ◽

Lupus Erythematosus ◽

Clinical Manifestations ◽

Serum Levels ◽

Organ Damage ◽

Inactive Disease ◽

Control Group ◽

Healthy Controls ◽

Sledai Score ◽

Active Disease

Systemic lupus erythematosus (SLE) is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1βwere found to be significantly higher in SLE patients than healthy controls (P<0.001). Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL) was significantly higher (P=0.0430) than those of inactive disease patients (43.85±63.36 pg/mL). Mean level of TNF-αwas44.76±68.32 pg/mL for patients with active disease while it was25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161). Similar results were obtained for IL-1β(P=0.0002). Correlation between IL-6, TNF-α, and IL-1βserum levels and SLEDAI score was observed (r=0.20,r=0.27, andr=0.38, resp.). This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease.

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Is there any correlation between high sensitive CRP and disease activity in systemic lupus erythematosus?

Lupus ◽

10.1177/0961203311418706 ◽

2011 ◽

Vol 20 (14) ◽

pp. 1494-1500 ◽

Cited By ~ 31

Author(s):

Z Rezaieyazdi ◽

M Sahebari ◽

MR Hatef ◽

B Abbasi ◽

H Rafatpanah ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Systemic Lupus ◽

Hs Crp

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher ( p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 ( p = 0.003, rs = −0.2) and C4 ( p = 0.02, rs = −0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.

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Evaluation of a Shared Autoimmune Disease-associated Polymorphism of TRAF6 in Systemic Sclerosis and Giant Cell Arteritis

The Journal of Rheumatology ◽

10.3899/jrheum.120038 ◽

2012 ◽

Vol 39 (6) ◽

pp. 1275-1279 ◽

Cited By ~ 2

Author(s):

F. DAVID CARMONA ◽

AURORA SERRANO ◽

LUIS RODRÍGUEZ-RODRÍGUEZ ◽

JOSÉ LUIS CALLEJAS ◽

CARMEN P. SIMEÓN ◽

...

Keyword(s):

Systemic Sclerosis ◽

Giant Cell Arteritis ◽

Giant Cell ◽

Lupus Erythematosus ◽

Genetic Network ◽

Healthy Controls ◽

Nucleotide Polymorphism ◽

Common Risk Factor ◽

Single Nucleotide

Objective.We evaluated whether a single-nucleotide polymorphism (SNP) of theTRAF6gene previously associated with systemic lupus erythematosus and rheumatoid arthritis may be a common risk factor for systemic sclerosis (SSc) and giant cell arteritis (GCA).Methods.A total of 1185 patients with SSc, 479 patients with biopsy-proven GCA, and 1442 unrelated healthy controls of white Spanish origin were genotyped for the rs540386 variant using a specifically designed TaqMan©allele discrimination assay.Results.No significant associations of this SNP with global SSc or GCA were found. This was also the case when the potential associations of theTRAF6polymorphism with the main clinical phenotypes of the 2 diseases (e.g., limited cutaneous and diffuse cutaneous SSc, or presence of polymyalgia rheumatica and visual ischemic manifestations in GCA) were assessed.Conclusion.Our data do not support a role of the rs540386TRAF6variant as a key component of the genetic network underlying SSc and GCA.

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The Role of Mesenchymal Stem Cells in Decreasing Interleukin-12 Human Systemic Lupus Erythematosus

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.5120 ◽

2020 ◽

Vol 8 (A) ◽

pp. 787-792

Author(s):

Delfitri Munir ◽

Rodiah Rahmawaty Lubis ◽

Dewi Masyithah Darlan ◽

Agung Putra ◽

Iffan Allif

Keyword(s):

Systemic Lupus Erythematosus ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Interleukin 12 ◽

Control Group ◽

Systemic Lupus ◽

Control Group Design

BACKGROUND: Systemic lupus erythematosus (SLE) disease is characterized by a loss of self-tolerance leading to a local tissue inflammation up to a massive systemic organ-spesific inflammation. Mesenchymal stem cells (MSCs) present immunomodulatory properties to control the over-activating immune responses in SLE through several mechanisms. However, the capability of MSCs to decrease interleukin (IL)-12 production in in vitro remains unclear. AIM: The aim of this study was to investigate the role of MSCs in decreasing the level of IL-12 derived from peripheral blood mononuclear cells (PBMCs) of SLE patients. METHODS: This study used a post-test control group design using a coculture of PBMCs from SLE and healthy patients with MSCs as the subjects. This study included five groups: sham (Sh), control (C), and treatment groups (T) treated by a co-culture MSCs with PBMCs at ratio dose of 1:1 (T1), 1:25 (T2), and 1:50 (T3), respectively, for 72 hours of incubation. The IL-12 levels was analysed by cytometric bead array (CBA) of flow cytometry. RESULTS: This study showed a significant decrease of IL-12 levels (p < 0.05) in T1 and T2 after 72 hours incubation of co-culture MSCs with PBMCs from SLE patient. CONCLUSION: MSCs could decrease the level of IL-12 in PBMCs of human SLE to control the inflammation of SLE disease.

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Interleukin (IL)-1 family cytokine in primary immune thrombocytopenia: a comparison with systemic lupus erythematosus-associated thrombocytopenia

10.21203/rs.3.rs-17605/v1 ◽

2020 ◽

Author(s):

Yanxia Zhan ◽

Boting Wu ◽

Chanjuan liu ◽

Luya Cheng ◽

Lili Ji ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Platelet Count ◽

Lupus Erythematosus ◽

Immune Thrombocytopenia ◽

Serum Levels ◽

Healthy Controls ◽

Systemic Lupus ◽

Primary Immune Thrombocytopenia ◽

Polymerase Chain

Abstract Background : Primary immune thrombocytopenia (ITP) is an autoimmune-mediated disorder characterized by decreased platelet count. Systemic lupus erythematosus (SLE) is also an autoimmune disease which thrombocytopenia is a common hematologic manifestation. Interleukin (IL)-1 family cytokines are major proinflammatory and immunoregulatory mediators. This study aimed to investigate the role of IL-1 cytokines in patients with ITP and SLE and the potential pathophysiologic mechanism to differentiate SLE-associated thrombocytopenia (SLE-TP) from ITP. Methods : Multiplex cytokine assay and real-time polymerase chain reaction (RT-PCR) were used to measure the IL-1 cytokines in 17 newly diagnosed ITP patients, 17 SLE-TP patients, 19 SLE patients without thrombocytopenia (SLE-NTP) and 10 healthy controls. Results : The serum levels of IL-1β, IL-18, IL-36α, IL-36β, IL-36γ and IL-33 were decreased significantly in ITP patients as compared with SLE-TP, SLE-NTP patients and healthy controls ( p <0.05). There was no significantly difference in the serum level of IL-37 between ITP and SLE-TP patients, however, there is a positive correlation between platelet count with IL-37 level in ITP patients. Our data suggested that serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, IL-33 and IL-37 were involved in the pathogenesis of ITP. Conclusions : Serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ and IL-33 could be considered biomarkers to differentiate SLE-TP from ITP patients.

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