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

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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Increased Proportion of CD226+ B Cells Is Associated With the Disease Activity and Prognosis of Systemic Lupus Erythematosus

Frontiers in Immunology ◽

10.3389/fimmu.2021.713225 ◽

2021 ◽

Vol 12 ◽

Author(s):

Miki Nakano ◽

Masahiro Ayano ◽

Kazuo Kushimoto ◽

Shotaro Kawano ◽

Kazuhiko Higashioka ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cells ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Renal Involvement ◽

Laboratory Data ◽

Clinical Manifestations ◽

Systemic Lupus ◽

Dsdna Antibody

BackgroundCD226, an activating receptor expressed on the surface of natural killer (NK) cells and T cells, is also seen on B cells and CD226 polymorphism is associated with systemic lupus erythematosus (SLE). Because the specific roles of CD226+ B cells in SLE are still unknown, we investigated the association of CD226+ B cells with SLE.MethodsWe measured CD226 expression on B cells and its subsets using flow cytometry in 48 SLE patients and 24 healthy controls (HCs). We assessed the relationships between CD226+ B cells and SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and prognosis after 12 months.ResultsThe proportions of CD226+ cells in whole B cells and all its subsets were significantly higher in SLE patients than HCs. In SLE patients, the proportions of CD226+ B cells and CD226+ switched-memory (SM) B cells were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers, and negatively correlated with serum complement levels. Moreover, basal percentages of CD226+ B cells and CD226+ SM B cells were low in patients who were in Lupus Low Disease Activity State after 12 months. In patients with renal involvement, the proportion of CD226+ B cells increased. Additionally, the proportion of CD226+ B cells was higher in patients who were not in complete renal remission after 12 months.ConclusionsIncreased proportion of CD226+ B cells was associated with disease activity and prognosis of SLE. CD226+ B cells may be a useful biomarker for the management of SLE.

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Elevated levels of IL-24 in systemic lupus erythematosus patients

Lupus ◽

10.1177/0961203319845476 ◽

2019 ◽

Vol 28 (6) ◽

pp. 748-754 ◽

Cited By ~ 1

Author(s):

R C Li ◽

J Guo ◽

L C Su ◽

A F Huang

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Inflammatory Cytokine ◽

Activity Index ◽

Clinical Manifestations ◽

Mrna Levels ◽

Healthy Controls ◽

Systemic Lupus ◽

Good Ability

Objective This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. Results Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. Conclusion The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.

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Polymorphisms of MFGE8 are associated with susceptibility and clinical manifestations through gene expression modulation in Koreans with systemic lupus erythematosus

Scientific Reports ◽

10.1038/s41598-019-55061-6 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Wook-Young Baek ◽

Ji-Min Woo ◽

Hyoun-Ah Kim ◽

Ju-Yang Jung ◽

Chang-Hee Suh

Keyword(s):

Gene Expression ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Milk Fat ◽

Clinical Manifestations ◽

Αvβ3 Integrin ◽

Apoptotic Cells ◽

Systemic Lupus ◽

Dsdna Antibody

AbstractSystemic lupus erythematosus (SLE) is characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor 8 (MFGE8) is a protein that connects αvβ3 integrin on phagocytic macrophages with phosphatidylserine on apoptotic cells. We investigated whether genetic variation of the MFGE8 gene and serum MFGE8 concentration are associated with SLE. Single nucleotide polymorphisms (SNPs) were genotyped and serum concentrations were analyzed. The rs2271715 C allele and rs3743388 G allele showed higher frequency in SLE than in healthy subjects (HSs). Three haplotypes were found among 4 SNPs (rs4945, rs1878327, rs2271715, and rs3743388): AACG, CGCG, and CGTC. CGCG haplotype was significantly more common in SLE than in HSs. rs4945 was associated with the erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-dsDNA antibody, and high disease activity. rs2271715 and rs3743388 were associated with renal disease, cumulative glucocorticoid dose, and cyclophosphamide and mycophenolate mofetil use. Serum MFGE8 concentrations were significantly higher in SLE than in HSs. Furthermore, the levels of MFGE8 were significantly higher in SLE than HSs of the rs2271715 CC genotype. In conclusion, MFGE8 genetic polymorphisms are associated not only with susceptibility to SLE but also with disease activity through modulation of gene expression.

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Clinical evaluation of total and high-avidity anti-dsDNA antibody assays for the diagnosis of systemic lupus erythematosus

Lupus ◽

10.1177/0961203319877243 ◽

2019 ◽

Vol 28 (12) ◽

pp. 1387-1396 ◽

Cited By ~ 1

Author(s):

W Yuan ◽

H Cao ◽

P Wan ◽

R Shi ◽

S Zhou ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Clinical Manifestations ◽

Superior Performance ◽

High Avidity ◽

Systemic Lupus ◽

Dsdna Antibody ◽

In Vitro Diagnostic

Background This study evaluated the diagnostic performances of total and high-avidity (HA) anti-dsDNA enzyme immunoassays (EIA) in Chinese systemic lupus erythematosus (SLE) patients. Methods A total of 410 serum samples from 217 SLE patients, 54 patients with other systemic autoimmune diseases, and 139 healthy subjects were tested on total and HA anti-dsDNA EIA, as well as three commercial in vitro diagnostic kits: BioPlex 2200 ANA Screen, Kallestad anti-dsDNA EIA, and Crithidia Lucilae IFA. The disease activities of SLE patients were assessed using the modified SLE Disease Activity Index. The diagnostic performances of each assay were analyzed using Analyse-it software. Results The diagnostic performances of the total and HA anti-dsDNA EIA kits were comparable to other commercially available in vitro diagnostic assays. Receiver operating characteristic curve analysis demonstrated an area under the curve ranging from 0.85 to 0.89, with the total anti-dsDNA kit demonstrating the highest sensitivity and the HA kit showing higher specificity. An overall agreement of >90% was observed between the total and HA anti-dsDNA EIA kits and commercially available quantitative anti-dsDNA kits. The ratio of HA to total anti-dsDNA antibody was significantly higher among SLE patients with active disease status and/or kidney damage. All assays exhibited a significant correlation with disease activity and multiple clinical manifestations. Conclusions While the clinical performances of various anti-dsDNA assays showed adequate agreements, the BioPlex 2200 anti-dsDNA assay demonstrated the highest positive likelihood ratio and odds ratio. The HA anti-dsDNA EIA kit in association with the total anti-dsDNA kit provided superior performance in SLE diagnosis and monitoring disease activity.

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Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance and disease activity in systemic lupus erythematosus: a cross-sectional human study

Lupus ◽

10.1177/0961203317691368 ◽

2017 ◽

Vol 26 (9) ◽

pp. 975-982 ◽

Cited By ~ 4

Author(s):

M Sahebari ◽

G Roshandel ◽

N Saadati ◽

M Saghafi ◽

N Abdolahi ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Human Study ◽

Serum Levels ◽

Inactive Disease ◽

Healthy Controls ◽

Systemic Lupus ◽

Positive Correlation ◽

Active Patients

Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls. Of those, 39 patients had active and 11 patients had inactive disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special method. Results There was no difference in levels of LL-37 between patients and healthy controls (50.9 ± 20.8 vs. 67.7 ± 43.3 ng/ml, P = 0.31). LL-37 did not correlate with SLEDAI and its items in total patients. LL-37 had a positive correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active patients (78% of patients), multivariate regression analysis showed significant negative correlation between LL-37 and C3 ( P = 0.01, standardized beta –0.50). No difference was found in levels of PAB between patients and controls (90.4 ± 34.1 vs. 86.9 ± 25.6 HK, P = 0.4).There was no difference in the levels of PAB between patients with active and inactive disease (93.2 ± 34.1 vs. 80.2 ± 33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI items and total score. However, a positive correlation between the levels of LL-37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on this study, serum LL-37 and PAB did not increase in lupus compared with healthy individuals. LL-37 serum values rose in parallel with SLEDAI in active disease. Positive correlation between serum PAB and LL-37 could be a great achievement of this study that may suggest the role of antioxidants in controlling NETosis.

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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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Predictors of Incident Seizure in Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.150135 ◽

2016 ◽

Vol 43 (3) ◽

pp. 565-575 ◽

Cited By ~ 12

Author(s):

XiangYang Huang ◽

Laurence S. Magder ◽

Michelle Petri

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Renal Involvement ◽

Multivariable Analysis ◽

Clinical Manifestations ◽

Systemic Lupus ◽

Malar Rash ◽

History Of

Objective.The risk factors for incident seizures in systemic lupus erythematosus (SLE) were prospectively determined in a cohort study.Methods.A total of 2203 patients with SLE followed longitudinally in the Hopkins Lupus Cohort were analyzed. Demographic variables, clinical manifestations, laboratory tests, and SLE disease activity were recorded at each quarterly visit. Adjusted estimates of association of risk factors for onset of seizure were derived using pooled logistic regression. We examined incident seizures in 3 ways: at the time of diagnosis, more than 45 days after the diagnosis of SLE, and after cohort entry.Results.Of 2203 patients with no history of seizure prior to SLE diagnosis, 157 (7.13%) had the first seizure occurrence at the time of (37 patients, 1.68%) or after diagnosis (120 patients, 5.45%) of SLE. The risk of seizure occurring around the time of SLE diagnosis was higher in patients with a history of malar rash (p = 0.002), proteinuria (p = 0.004), and psychosis (p < 0.001). Multivariable analysis of the first seizure occurring after the diagnosis of SLE showed that history of low C3 (p = 0.0078), psychosis (p < 0.0001), cranial or peripheral neuropathy (p = 0.0043), anti-Sm antibody (p = 0.0551), renal involvement (p = 0.0177), and current corticosteroid dose (p < 0.0001) were independently associated with a higher incidence of seizure. Disease activity was not predictive after adjusting for corticosteroids.Conclusion.Risk of seizure after diagnosis of SLE is increased in those patients with prior psychosis, neuropathy, proteinuria, anti-Sm, low C3, and use of corticosteroids.

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Elevated Serum Levels of Syndecan-1 Are Associated with Renal Involvement in Patients with Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.140568 ◽

2014 ◽

Vol 42 (2) ◽

pp. 202-209 ◽

Cited By ~ 13

Author(s):

Ki-Jo Kim ◽

Ji-Young Kim ◽

In-Woon Baek ◽

Wan-Uk Kim ◽

Chul-Soo Cho

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Activity Index ◽

Renal Involvement ◽

Elevated Serum ◽

Clinical Manifestations ◽

Major Constituent ◽

Systemic Lupus ◽

Filtration Barrier ◽

Dsdna Antibody

Objective.Syndecan-1 (SDC-1) is a major constituent of the endothelial glycocalyx, which plays a role in maintaining vascular homeostasis and functions as a glomerular filtration barrier. SDC-1 is readily shed into the blood under various conditions, but the clinical implication of circulating SDC-1 in patients with systemic lupus erythematosus (SLE) remains unclear. We aimed to investigate the association of serum SDC-1 level with certain clinical manifestations of SLE.Methods.We measured serum SDC-1 levels by ELISA in 111 patients with SLE, 18 with rheumatoid arthritis (RA), and 20 healthy subjects, and investigated its association with clinical manifestations and laboratory variables.Results.Serum SDC-1 levels were higher in patients with SLE than in those with RA and healthy controls (both p < 0.001) and were positively correlated with SLE Disease Activity Index (SLEDAI; r = 0.367, p < 0.001) and anti-dsDNA antibody level (r = 0.259, p = 0.007), but inversely correlated with serum C3 and CH50 levels (r = −0.305, p = 0.001 and r = −0.244, p = 0.012). Patients with active nephritis had higher serum SDC-1 levels than patients with inactive nephritis and those without nephritis (both p < 0.001). In addition, serum SDC-1 levels were correlated with renal SLEDAI score (r = 0.540, p < 0.001) and excretion of proteinuria as measured by spot urine protein/creatinine ratio (r = 0.538, p < 0.001). In 14 patients with lupus nephritis (LN) whose serum samples were obtained at the time of renal biopsy, there was a positive correlation between serum SDC-1 levels and activity index (r = 0.632, p = 0.015).Conclusion.Serum SDC-1 levels are increased in SLE patients with nephritis, indicating that SDC-1 might be a useful serum biomarker for active LN.

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Nailfold capillaroscopic changes in patients with systemic lupus erythematosus: correlations with disease activity, skin manifestation and nephritis

Lupus ◽

10.1177/0961203316686702 ◽

2017 ◽

Vol 26 (9) ◽

pp. 959-966 ◽

Cited By ~ 11

Author(s):

S Shenavandeh ◽

S Habibi

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Morphological Changes ◽

Cell Damage ◽

Renal Involvement ◽

Laboratory Data ◽

Clinical Manifestations ◽

Skin Involvement ◽

Systemic Lupus

Introduction The clinical expression of systemic lupus erythematosus (SLE) is the consequence of endothelial cell damage leading to serious multiple organ dysfunction. The aim of this study was to assess the association between nailfold capillaroscopic changes and disease activity, skin and renal involvement in patients with SLE. Methods Demographic variables, clinical manifestations and laboratory data of 108 patients with SLE were investigated. Nailfold capillaroscopy (NFC) was performed in all patients. Result Morphological changes in NFC were observed in 102 out of 108 (94.4%) SLE patients. Minor changes were found in 33 (30.6%) and major changes in 69 (63.9%) cases. The disease activity was significantly higher in the patients with major changes ( p < 0.002). A higher incidence of microhaemorrhages was seen in patients with active SLE disease ( p < 0.04). In SLE patients with active skin involvement, the disturbed distribution ( p < 0.004) was more frequent and subtle changes ( p < 0.009) were less frequently observed as compared with patients without active skin involvement. In the group of SLE patients with renal involvement, no correlation was found between the capillary abnormalities and the presence of renal involvement ( p > 0.05), except for the elongated capillary loops, which were seen more often in patients with renal involvement than in patients without it ( p < 0.03). Conclusion The results of the study showed that capillary changes (abnormal capillaroscopy) were very common in patients with SLE, although there were no specific patterns like the ones in scleroderma patients, and some changes may be associated with disease activity, especially in patients with active skin involvement.

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