Salivary Immunoglobulin Gamma-3 Chain C Is a Promising Noninvasive Biomarker for Systemic Lupus Erythematosus

We aimed to characterize the salivary protein components and identify biomarkers in patients with systemic lupus erythematosus (SLE). A proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry was performed to determine the alterations of salivary proteins between patients with SLE and healthy controls, and the concentrations of the candidate proteins were measured through Western blot analysis and the enzyme-linked immunosorbent assay. The 10 differentially expressed protein spots were immunoglobulin gamma-3 chain C region (IGHG3), immunoglobulin alpha-1 chain C region, protein S100A8, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels compared to patients with rheumatoid arthritis (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively; p < 0.001 for both) or healthy controls (2.2 ± 1.64 pg/mL and 2.2 ± 1.7 pg/mL, respectively; p < 0.001 for both). The salivary IGHG3 levels correlated with the erythrocyte sedimentation rate (r = 0.26, p = 0.01), anti-double-stranded DNA (dsDNA) antibody levels (r = 0.25, p = 0.01), and nephritis (r = 0.28, p = 0.01). The proteomic analysis revealed that the salivary IGHG3 levels were associated with SLE and lupus disease activity, suggesting that salivary IGHG3 may be a promising noninvasive biomarker for SLE.

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Proteomic analysis identified salivary immunoglobulin gamma-3 chain C as a potential biomarker for systemic lupus erythematosus

10.21203/rs.3.rs-23170/v1 ◽

2020 ◽

Author(s):

Ju-Yang Jung ◽

Jin-Young Nam ◽

Keun-Sil Ryu ◽

Joo-Ho Shin ◽

Sung- Min Lee ◽

...

Keyword(s):

Mass Spectrometry ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Proteomic Analysis ◽

Gel Electrophoresis ◽

Deoxyribonucleic Acid ◽

Mass Spectrometry Analysis ◽

Healthy Controls ◽

Systemic Lupus ◽

Immunoglobulin Gamma

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies and systemic inflammatory response. We aimed to characterize the salivary protein components and find biomarkers in patients with SLE. Methods The pooled salivary proteins of patients with SLE and healthy controls were subjected to 2-dimensional gel electrophoresis. The spots exhibiting > 2-fold intensity change between SLE and healthy controls were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Results The proteomic analysis using 2-dimensional gel electrophoresis and mass spectrometry revealed 10 differentially expressed protein spots, which included immunoglobulin gamma-3 chain C region (IGHG3), immunoglobulin alpha-1 chain C region (IGHA1), protein S100, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine deoxyribonucleic acid glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels than patients with rheumatoid arthritis (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively, p < 0.001 for both) or healthy controls (2.2 ± 1.64 pg/mL and 2.2 ± 1.7 pg/mL, respectively, p < 0.001 for both). The salivary IGHG3 levels correlated with erythrocyte sedimentation rate (r = 0.26, p = 0.01), anti-double-strand deoxyribonucleic acid antibody levels (r = 0.25, p = 0.01), and nephritis (r = 0.28, p = 0.01). Conclusions Patients with SLE exhibited elevated salivary IGHG3 and lactoferrin levels, and the salivary IGHG3 levels correlated with disease activity markers of SLE. Salivary IGHG3 may be a promising non-invasive biomarker in SLE.

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Dysregulated T Cell Activation and Aberrant Cytokine Expression Profile in Systemic Lupus Erythematosus

Mediators of Inflammation ◽

10.1155/2019/8450947 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Haiyan Zhou ◽

Bojiang Li ◽

Jing Li ◽

Tongqian Wu ◽

Xiaoqian Jin ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

T Cell ◽

Lupus Erythematosus ◽

Critical Role ◽

Cytokine Expression ◽

Healthy Controls ◽

Systemic Lupus ◽

Hla Dr ◽

Dsdna Antibody

Accumulating evidence indicates a critical role for T cells and relevant cytokines in the pathogenesis of systemic lupus erythematosus (SLE). However, the specific contribution of T cells together with the related circulating cytokines in disease pathogenesis and organ involvement is still not clear. In the current study, we investigated relevant molecule expressions and cytokine levels in blood samples from 49 SLE patients and 22 healthy control subjects. The expression of HLA-DR and costimulatory molecules on T cells was evaluated by flow cytometry. Concentrations of serum C-reactive protein, erythrocyte sedimentation rate, anti-double-stranded DNA (anti-dsDNA) antibody, total lgG, complement 3, and complement 4 were measured. Serum cytokines and chemokines were measured by a cytometric bead array assay. Elevated frequencies of HLA-DR+ T cells and ICOS+ T cells were observed in SLE patients with positive anti-dsDNA antibodies compared with those in healthy controls (P<0.001). The expression of HLA-DR+ T cells was positively correlated with SLEDAI (r=0.15, P<0.01). Furthermore, levels of serum IL-6, MCP-1, TNFRI, IL-10, IL-12, and CCL20 were higher in SLE patients compared with healthy controls. In addition, patients with hematologic manifestations displayed elevated frequencies of HLA-DR+ T cells and ICOS+ T cells. Patients with renal manifestations had a decreased frequency of TIGIT+ T cells. These results suggested a dysregulated T cell activity and cytokine expression profiles in SLE subjects. We also developed a chemokine and cytokine profiling strategy to predict the activity of SLE, which has clinical implication for better monitoring the flares and remission during the course of SLE and for assessing therapeutic interventions.

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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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Association of Elevated Serum Soluble Cd226 Levels With the Disease Activity and Flares of Systemic Lupus Erythematosus

10.21203/rs.3.rs-377056/v1 ◽

2021 ◽

Author(s):

Miki Nakano ◽

Masahiro Ayano ◽

Kazuo Kushimoto ◽

Shotaro Kawano ◽

Kazuhiko Higashioka ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Laboratory Data ◽

Elevated Serum ◽

Soluble Form ◽

Enzyme Linked Immunosorbent Assay ◽

Cumulative Probability ◽

Systemic Lupus ◽

Dsdna Antibody

Abstract Background: CD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. A soluble form of CD226 (sCD226) is known to be shed from the membrane type of CD226 (mCD226). Although CD226 polymorphism and mCD226 are known to be involved in systemic lupus erythematosus (SLE), the involvement of sCD226 in SLE is still unknown. Therefore, we aimed to reveal the association of sCD226 with SLE.Methods: We measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, and laboratory data. We defined the maximum values of sCD226 in HCs as a cut-off level and compared the cumulative probability of flare for patients with high and low sCD226 levels. Results: Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. Conclusion: Serum sCD226 levels were associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.

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miR-183-5p Is a Potential Molecular Marker of Systemic Lupus Erythematosus

Journal of Immunology Research ◽

10.1155/2021/5547635 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Shaolan Zhou ◽

Jing Zhang ◽

Pengfei Luan ◽

Zhanbing Ma ◽

Jie Dang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Diagnostic Performance ◽

Activity Index ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Healthy Controls ◽

Systemic Lupus ◽

Candidate Mirnas ◽

Dsdna Antibody

Objective. To investigate microRNA (miRNA) expression profiles in individuals with systemic lupus erythematosus (SLE) and identify the valuable miRNA biomarkers in diagnosing and monitoring SLE. Methods. Next-generation sequencing (NGS) was performed to assess miRNA amounts in peripheral blood mononuclear cells (PBMCs) from four SLE cases and four healthy controls. Quantitative polymerase chain reaction (qPCR) was carried out for validating candidate miRNAs in 32 SLE cases and 32 healthy controls. In addition, receiver operating characteristic (ROC) curve analysis was completed to evaluate diagnostic performance. Finally, the associations of candidate miRNAs with various characteristics of SLE were analyzed. Results. A total of 157 miRNAs were upregulated, and 110 miRNAs were downregulated in PBMCs from SLE cases in comparison to healthy controls, of which the increase of miR-183-5p and decrease of miR-374b-3p were validated by qPCR and both showed good diagnostic performance for SLE diagnosis. Besides, miR-183-5p expression levels displayed a positive association with SLE disease activity index (SLEDAI) and anti-dsDNA antibody amounts. Conclusion. Our data indicated that miR-183-5p is a promising biomarker of SLE.

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Collagen triple helix repeat containing-1: a novel biomarker associated with disease activity in Systemic lupus erythematosus

Lupus ◽

10.1177/0961203318804877 ◽

2018 ◽

Vol 27 (13) ◽

pp. 2076-2085 ◽

Cited By ~ 1

Author(s):

Q Wu ◽

Q Yang ◽

H Sun

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Triple Helix ◽

Inactive Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Systemic Lupus ◽

Sledai Score ◽

Collagen Triple Helix

Objective The objective of this article is to investigate whether the aberrant expression of collagen triple helix repeat containing-1 (CTHRC1) from patients with systemic lupus erythematosus (SLE) could contribute to the pathogenesis of lupus. Methods We divided SLE patients into active groups (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥ 6) and inactive groups (SLEDAI score < 6). Serum concentrations of CTHRC1, interferon alpha, interleukin (IL)-28A and IL-28B were determined using an enzyme-linked immunosorbent assay in a group of 40 patients with SLE. Results were compared with those from 23 healthy controls. Results Serum CTHRC1 protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease displayed higher CTHRC1 levels compared with those with inactive disease as well. There was a positive association between serum CTHRC1 levels and SLEDAI and erythrocyte sedimentation rate, and a negative correlation with complement 3 and 4. Moreover, serum CTHRC1 levels were higher in SLE patients with arthritis and anemia compared with patients without the above-mentioned manifestations. Conclusions These findings indicate CTHRC1 probably plays an important part in the pathogenesis of SLE, and is positively associated with disease activity, while it also likely refers to the development of arthritis and anemia in SLE. Therefore, CTHRC1 may provide a novel research target and shed new light on the pathogenesis and therapy of SLE.

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Association of elevated serum soluble CD226 levels with the disease activity and flares of systemic lupus erythematosus

Scientific Reports ◽

10.1038/s41598-021-95711-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Miki Nakano ◽

Masahiro Ayano ◽

Kazuo Kushimoto ◽

Shotaro Kawano ◽

Kazuhiko Higashioka ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Laboratory Data ◽

Elevated Serum ◽

Clinical Manifestations ◽

Enzyme Linked Immunosorbent Assay ◽

Cumulative Probability ◽

Systemic Lupus ◽

Dsdna Antibody

AbstractCD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. Although CD226 polymorphism is known to be involved in systemic lupus erythematosus (SLE), the involvement of soluble CD226 (sCD226) in SLE is still unknown. In the present study, we measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and the cumulative probability of flare. Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥ 20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. These findings indicate that serum sCD226 levels are associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.

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Correlation of Circulating Glucocorticoid-Induced TNFR-Related Protein Ligand Levels with Disease Activity in Patients with Systemic Lupus Erythematosus

Clinical and Developmental Immunology ◽

10.1155/2012/265868 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Lei Gu ◽

Lingxiao Xu ◽

Xiaojun Zhang ◽

Wenfeng Tan ◽

Hong Wang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Renal Involvement ◽

Clinical Manifestations ◽

Inactive Disease ◽

Healthy Controls ◽

Related Protein ◽

Systemic Lupus ◽

Dsdna Antibody

The aim of this paper is to investigate the correlation of glucocorticoid-induced tumor necrosis factor receptor- (TNFR-) related protein ligand (GITRL) with disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Serum GITRL levels were measured in 58 patients with SLE and 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of serum GITRL levels with SLEDAI, laboratory values, and clinical manifestations were assessed. Serum GITRL levels were determined by ELISA. Serum GITRL levels were markedly increased in patients with SLE compared with healthy controls (mean 401.3 ng/mL and 36.59 ng/mL, resp.;P<0.0001). SLE patients with active disease showed higher serum GITRL levels compared to those with inactive disease (mean 403.3 ng/mL and 136.3 ng/mL, resp;P=0.0043) as well as normal controls (36.59 ng/mL;P<0.0001). Serum GITRL levels were positively correlated with SLEDAI, titers of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), and IgM and negatively correlated with complement3 (C3). Serum GITRL levels were higher in SLE patients with renal involvement and vasculitis compared with patients without the above-mentioned manifestations.

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Gene polymorphisms and serum levels of sVEGFR-1 in patients with systemic lupus erythematosus

Scientific Reports ◽

10.1038/s41598-020-72020-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Zhi-Chao Yuan ◽

Wang-Dong Xu ◽

Jia-Min Wang ◽

Qian Wu ◽

Jie Zhou ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Gene Polymorphisms ◽

Growth Factor Receptor ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Systemic Lupus ◽

Chinese Han

Abstract Correlation between soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentration, VEGFR1 gene polymorphisms and systemic lupus erythematosus (SLE) risk remains unclear. The present case–control study comprised 254 SLE patients, 385 other rheumatic diseases patients and 390 healthy controls. Serum levels of sVEGFR-1 were detected by enzyme-linked immunosorbent assay. Seven VEGFR1 genetic variants (rs2296188, rs9943922, rs2296283, rs7324510, rs9554322, rs9582036, rs9554320) were genotyped by KASP. Serum levels of sVEGFR-1 were up-regulated in SLE and positively correlated with disease activity. Furthermore, serum sVEGFR-1 presented a distinctive elevation in SLE in comparison with other rheumatic diseases. Frequencies of allele T of rs2296283 and allele G of rs9554322 were significant lower in SLE patients (P = 0.003, P = 0.004). Frequencies of genotypes TT of rs2296188 and rs2296283 were declined in patients compared with healthy controls (P = 0.039, P = 0.033). CC genotype of rs7324510 and rs9582036 was negatively correlated with SLE risk (OR = 0.538, OR = 0.508). Distribution of GG, GC, GG + GC genotypes of rs9554322 were different between SLE patients and healthy controls (P = 0.027, P = 0.036, P = 0.010). Moreover, frequency of TC genotype of rs7324510 was higher in SLE patients with lupus headache (χ2 = 9.924, P = 0.039) and frequency of TC genotype of rs9943922 was lower in patients with cylindruriain (χ2 = 7.589, P = 0.026). Frequencies of allele C of rs7324510 and allele T of rs9943922 were decreased in SLE patients with cylindruria and hypocomplementemia, respectively (χ2 = 4.195, P = 0.041, χ2 = 3.971, P = 0.046). However, frequency of allele C of rs9554322 was increased in SLE patients with pyuria (χ2 = 11.702, P = 0.001). In addition, SLE patients carrying GG, GC, CC genotypes for rs9554322 had higher levels of serum sVEGFR-1. In conclusion, serum sVEGFR-1 was elevated in SLE patients and may be a disease marker. VEGFR1 gene polymorphisms related to risk of SLE in a Chinese Han population.

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Association of Lipoprotein and Thyroid Hormones With Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus

10.21203/rs.3.rs-115002/v1 ◽

2020 ◽

Author(s):

Li Lu ◽

Wei Kong ◽

Kangxing Zhou ◽

Jinglei Chen ◽

Yayi Hou ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Cognitive Function ◽

Thyroid Hormones ◽

Cognitive Dysfunction ◽

Lupus Erythematosus ◽

Significant Negative Correlation ◽

Clinical Feature ◽

Enzyme Linked Immunosorbent Assay ◽

Systemic Lupus ◽

Dsdna Antibody

Abstract Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) occurs up to 75% of adult SLE patients, and is one of the major causes of death in SLE patients. Cognitive dysfunction is a typical clinical feature of NPSLE, which seriously affects the quality of life of patients. Dyslipidemia and thyroid disease, which were prevalent in SLE patients, both related to the neuropsychiatric disturbances, including significant psychiatric and cognitive disturbance. This study aimed to investigate whether cognitive dysfunction in patients with systemic lupus erythematosus (SLE) was related to the expression of serum thyroid hormone and lipoproteins.Methods: A total of 121 patients with SLE and 65 healthy controls (HCs) at Nanjing Drum Tower Hospital completed a cognitive function test, then 81 SLE patients were divided into high cognition (n=33) group and low cognition group (n=48). The differences in clinical and laboratory tests and the correlations between IgG, IgM, albumin, T3, and T4 levels and cognitive function were analyzed. The enzyme-linked immunosorbent assay was used to determine the serum levels of 4 lipoproteins (APOE, APOA1, IGF-1, and IGFBP7) in 81 patients.Results: Patients with SLE were less educated with abnormal cognitive function compared with HCs. The levels of albumin, T3 (P < 0.05), and T4 decreased in low-cognition patients, while D-dimer, anti-dsDNA antibody, and IgM levels increased. The serum IgG and IgM levels showed a significant negative correlation with partial cognitive function. The serum T3 and T4 levels positively correlated with cognition. The expression of APOE, APOA1, IGF-1, and IGFBP7 showed no difference between the high- and low-cognition groups. However, the serum APOE level negatively correlated with Line Orientation, APOA1 positively correlated with Coding, and IGFBP7 negatively correlated with Graphic copy (P < 0.05), and IGF-1 had no correlation with any cognitive functions.Conclusions: Thyroid hormones (T3 and T4) and lipoproteins (APOE, APOA1, and IGFBP7) were associated with cognitive dysfunction in SLE. Whether T3 and T4 can be used in clinical practice as the biomarkers of cognitive dysfunction in SLE needs further exploration.

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