The Relation of Interleukin 17 (IL-17) and IL-23 to Th1/Th2 Cytokines and Disease Activity in Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (10) ◽  
pp. 2046-2052 ◽  
Author(s):  
MO YIN MOK ◽  
HAI JING WU ◽  
YI LO ◽  
CHAK SING LAU
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Interleukin 17 ◽  
Healthy Controls ◽  
Th2 Cytokines ◽  
Systemic Lupus ◽  
Active Lupus Nephritis ◽  
Active Lupus ◽  
Active Disease

Objective.Interleukin 17 (IL-17) was recently linked to pathogenesis of systemic lupus erythematosus (SLE), but its relation to disease activity has not been well characterized. We examined the relation between serum levels of Th17 (IL-17, IL-23), Th1 (IL-12, interferon-γ), Th2 (IL-10, IL-6, IL-4) cytokines and disease activity in patients with SLE.Methods.Serum cytokines were measured by enzyme linked immunosorbent assays. Disease activity was determined by SLE disease activity index (SLEDAI), anti-dsDNA antibody, and C3 and C4 levels.Results.Serum levels of IL-17 (p < 0.001), IL-6 (p = 0.006) and IL-10 (p < 0.001) were higher in SLE patients (n = 70) compared to healthy controls (n = 36). Higher serum IL-23 level was found in patients with active disease with cutaneous manifestations (p = 0.004) and serositis (p = 0.04) compared to those without. Serum IL-17 level above the detection limit was more frequently found in patients who had active lupus nephritis (11/23, 47.8%) (p = 0.002), nonrenal active disease (9/15, 60%) (p = 0.001), and inactive lupus (21/32, 65.6%) (p < 0.001) compared to healthy controls (0%). Serum IL-17 levels were otherwise comparable between these 3 groups of patients and were not related to SLEDAI, glomerular filtration rate, activity or chronicity score and ISN/RPS criteria class among patients with active lupus nephritis. There was no significant correlation between serum IL-17/IL-23 and Th1 or Th2 cytokine levels.Conclusion.SLE patients had higher serum IL-17 levels than healthy controls. Elevated serum IL-23 was found in patients with inflammatory manifestations including cutaneous involvement and serositis. The lack of correlation between Th17, Th1, and Th2 cytokines suggested independent regulatory mechanisms for these cytokines.

scholarly journals The role of Dickkopf-1 as a biomarker in systemic lupus erythematosus and active lupus nephritis

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Mervat E. Abdelazeem ◽  
Marwa I. Abdelhaleem ◽  
Rabab A. Mohamed ◽  
Enas A. Abdelaleem
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Renal Diseases ◽  
Systemic Lupus ◽  
Active Lupus Nephritis ◽  
Active Lupus

Abstract Background Systemic lupus erythematosus (SLE) is a chronic disease which is mainly attributed to autoantibodies, cytokines, and immune complex deposition. Studies have demonstrated that cytokines and autoantibodies were strongly associated with renal diseases and can be used for the prediction of patients with lupus nephritis (LN). However, antibodies to dsDNA and the reduction of complements were also detected in non-LN patients as well as clinically non-active SLE patients. The current study was performed to detect the role of serum DKK-1 as a biomarker for the identification of SLE patients and patients with LN and its relation to disease activity and severity. The study was conducted on fifty clinically diagnosed SLE patients who were diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, in addition to thirty healthy control volunteers matched for age and sex. Assessment of SLE disease activity was done using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Assessment of SLE disease severity was done using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index. Serum levels of DKK-1 were measured for all participants by ELISA using commercially available kits. Results DKK-1 serum levels were significantly higher among active lupus nephritis cases as compared with SLE cases with no LN and with healthy controls (9197.60 μg/uL ± 2939.2 μg/uL vs. 6405.15 μg/uL ± 2018.91 μg/uL vs. 2790.33 μg/uL ± 833.49 μg/uL) respectively (p-values < 0.001). DKK-1 concentration was significantly higher among SLE patients with positive as compared with negative anti-double-stranded DNA (dsDNA) antibodies (p-value < 0.001). According to receiver operating characteristic (ROC) curve analysis, serum DKK-1 level diagnosed the SLE at a statistically significant level with a 98% sensitivity and 70% specificity and serum DKK-1 level also diagnosed active lupus nephritis at a 90% sensitivity and 63% specificity. Conclusion DKK-1 could diagnose SLE and lupus nephritis with high sensitivity and specificity. Serum DKK-1 is a reliable biomarker for the identification of SLE and patients with LN and could be used as a key molecule for the diagnosis of SLE and as a prognostic indicator of LN.

scholarly journals The association between serum prolactin levels and interleukin-6 and systemic lupus erythematosus activity

Reumatismo ◽  
2018 ◽  
Vol 70 (4) ◽  
pp. 241-250 ◽  
Author(s):  
W.A. Wan Asyraf ◽  
M.S. Mohd Shahrir ◽  
W. Asrul ◽  
A.W. Norasyikin ◽  
O. Hanita ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Prolactin Level ◽  
Serum Prolactin ◽  
Systemic Lupus ◽  
Serum Prolactin Level ◽  
Active Lupus Nephritis ◽  
Active Lupus

Based on the recent evidence of association between hyperprolactinemia and systemic lupus erythematosus disease activity (SLEDAI), a study was conducted to analyze the association of hyperprolactinemia with lupus nephritis disease activity. In this cross-sectional study, the analysis was conducted on SLE patients who visited the University Kebangsaan Malaysia Medical Centre (UKMMC) Nephrology Clinic from August 2015 till February 2016. The disease activity was measured using the SLEDAI score, with more than 4 indicating active lupus nephritis. Basal resting prolactin level was analyzed in 43 patients with lupus nephritis, in 27.9% of them had raised serum prolactin. The median of serum prolactin level at 0 minutes was 19.91 ng/mL (IQR: 15.95-22.65 ng/ mL) for active lupus nephritis, which was significantly higher compared to the median of serum prolactin level of 14.34 ng/mL (IQR: 11.09-18.70 ng/mL) for patients in remission (p=0.014). The serum prolactin level positively correlated with SLEDAI (rhos: 0.449, p=0.003) and the UPCI level in lupus nephritis patients (rhos: 0.241, p=0.032). The results were reproduced when the serum prolactin was repeated after 30 minutes. However, the serum prolactin levels at 0 minutes were higher than those taken after 30 minutes (p=0.001). An assessment of serum IL-6 levels found that the active lupus nephritis patients had a higher median level of 65.91 pg/ mL (IQR: 21.96-146.14 pg/mL) compared to the in-remission level of 15.84 pg/mL (IQR: 8.38-92.84 pg/mL), (p=0.039). Further correlation analysis revealed that there was no statistical correlation between the interleukin (IL)-6 levels with serum prolactin, SLEDAI and other lupus nephritis parameters. An ROC curve analysis of serum prolactin at 0 minutes and serum prolactin after 30 minutes and IL-6 levels for prediction of SLE disease activity provided the cutoff value of serum prolactin at 0 minutes, which was 14.63 ng/mL with a sensitivity of 91.7% and specificity of 58.1% and AUC of 0.74 (p=0.015). This study concurred with the previous findings that stated that hyperprolactinemia is prevalent in SLE patients and correlated with clinical disease activity and UPCI level. The baseline of the fasting serum prolactin level was found to be a sensitive biomarker for the evaluation of lupus nephritis disease activity.

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

Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
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.

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

Lupus ◽  
2017 ◽  
Vol 26 (9) ◽  
pp. 975-982 ◽  
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.

Antibodies against carbamylated vimentin exist in systemic lupus erythematosus and correlate with disease activity

Lupus ◽  
2020 ◽  
Vol 29 (3) ◽  
pp. 239-247 ◽  
Author(s):  
Y Li ◽  
R Jia ◽  
Y Liu ◽  
S Tang ◽  
X Ma ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Joint Damage ◽  
Serum Levels ◽  
Joint Involvement ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Clinical Value ◽  
Primary Sjögren Syndrome

Objectives Antibodies against carbamylated protein (anti-CarP) were found to be a promising marker to evaluate joint damage and disease activity in patients with rheumatoid arthritis (RA). However, whether anti-CarP antibodies were present in systemic lupus erythematosus (SLE) remained ambiguous. We have therefore undertaken this study to assess the levels of serum anti-CarP antibodies and to evaluate their clinical value in SLE. Methods Serum levels of antibodies against carbamylated-vimentin (anti-Carp) were measured by enzyme immunosorbent assay in 100 patients with SLE, 76 with RA, 17 with primary Sjögren syndrome (pSS), and 68 healthy controls. Data analyses between anti-Carp antibodies and other laboratory measures were performed using SPSS 24 software for Windows. Results The levels of serum anti-CarP antibodies in patients with SLE were significantly higher than those in healthy controls. In addition, anti-CarP antibodies were present in SLE patients lacking the disease-specific antibodies, including anti-Smith–negative patients (24.4%, 21/86), anti-dsDNA–negative patients (29.3%, 12/41), anti-nucleosome–negative patients (21.4%, 9/42), and antiribosomal P protein antibody–negative patients (23.7%, 18/76). There were significant differences between the anti-CarP–positive and anti-CarP–negative SLE patients in clinical and laboratory features, such as age, erythrocyte sedimentation rate (ESR), C-reactive protein, rheumatoid factor, third-generation cyclic citrullinated peptide (CCP3), anticardiolipin, D-dipolymer, complement 3, immunoglobulin G (IgG), red blood cell count (RBC) and hemoglobin. After adjusting for age and disease duration, the high levels of anti-CarP antibodies were still correlated with low RBC, hemoglobin and high ESR, IgG and CCP3. Active SLE patients demonstrated higher anti-CarP IgG than inactive patients. Moreover, the levels of anti-CarP were significantly higher in SLE patients with arthralgia and/or arthritis than in those without joint involvement. Conclusions Anti-CarP antibodies were present in SLE patients and associated with the disease severity. These might provide a potential supplement to other specific autoantibodies for diagnosis of SLE and serve as a promising marker for measuring joint damage in the disease.

Serum levels of soluble programmed cell death protein 1 and soluble programmed cell death protein ligand 2 are increased in systemic lupus erythematosus and associated with the disease activity

Lupus ◽  
2020 ◽  
Vol 29 (7) ◽  
pp. 686-696
Author(s):  
Shinya Hirahara ◽  
Yasuhiro Katsumata ◽  
Hidenaga Kawasumi ◽  
Yashushi Kawaguchi ◽  
Masayoshi Harigai
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Dsdna Antibodies ◽  
Cell Death Protein

Objective Programmed cell death protein 1 (PD-1) pathway plays important roles in systemic lupus erythematosus (SLE). We aimed to elucidate the association of serum soluble PD-1 (sPD-1) and related molecules with SLE and to explore their usefulness as biomarkers. Methods We retrospectively measured the serum levels of sPD-1, soluble PD-ligand 1 (sPD-L1), soluble PD-ligand 2 (sPD-L2) and interleukin (IL)-21 by ELISA in SLE patients, systemic sclerosis patients and healthy controls. Repeat sera samples were also obtained post treatment. Results The serum levels of sPD-1 and sPD-L2 in SLE patients with high disease activity were significantly higher than those in SLE patients with low disease activity, systemic sclerosis patients and healthy controls ( n = 58, 15, 20 and 21, respectively; p < 0.001). However, the serum levels of sPD-L1 and IL-21 were not elevated in SLE patients. The serum levels of sPD-1 and sPD-L2 were higher among active SLE patients who tested positive for anti-dsDNA antibodies than in those who tested negative ( p = 0.002 and <0.001, respectively). There were moderate correlations between the serum levels of sPD-1 and sPD-L2 and the SLE Disease Activity Index 2000 scores, the titres of anti-dsDNA antibodies and the serum levels of complements. Furthermore, the serum levels of sPD-1 and sPD-L2 decreased significantly in accordance with disease amelioration following treatment ( p < 0.001). Conclusion The present study demonstrated the association of serum sPD-1 and sPD-L2 with SLE and suggests their usefulness as disease activity biomarkers for SLE.

Growing international evidence for urinary biomarker panels identifying lupus nephritis in children – verification within the South African Paediatric Lupus Cohort

Lupus ◽  
2018 ◽  
Vol 27 (14) ◽  
pp. 2190-2199 ◽  
Author(s):  
E M D Smith ◽  
L B Lewandowski ◽  
A L Jorgensen ◽  
A Phuti ◽  
P Nourse ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
South African ◽  
Lupus Erythematosus ◽  
Healthy Controls ◽  
Urinary Biomarker ◽  
Systemic Lupus ◽  
Juvenile Onset ◽  
Active Lupus Nephritis ◽  
Active Lupus ◽  
Onset Systemic Lupus Erythematosus

Background A urinary biomarker panel including alpha-1-acid-glycoprotein (AGP), lipocalin-like-prostaglandin-D-synthase (LPGDS), transferrin and ceruloplasmin demonstrates an ‘excellent’ ability for identifying active lupus nephritis in UK/US children. This study aimed to assess whether this panel identifies active lupus nephritis within the South African Paediatric Lupus Cohort. Methods Juvenile-onset-systemic lupus erythematosus (JSLE) patients aged < 19 years at diagnosis and healthy controls were recruited. Patients were categorized as having active lupus nephritis (renal BILAG score; A/B and previous histological confirmation) or inactive lupus nephritis (renal BILAG score: D/E). Urinary biomarkers were quantified by ELISA. Mann–Whitney U-test compared biomarker levels between groups. Binary logistic regression and receiver operating curve analysis assessed biomarker combinations. Results Twenty-three juvenile-onset-systemic lupus erythematosus patients were recruited with a median age of 13.5 years (interquartile range (IQR) 12.7–14.9) and disease duration of 2.6 years (IQR 1.8–4.0). Eighteen healthy controls had a median age of 11.0 years (IQR 10.0–12.0). AGP, LPGDS, transferrin, ceruloplasmin and VCAM-1 were significantly higher in active than in inactive lupus nephritis patients (corrected p-values, all pc < 0.05), with no difference between inactive lupus nephritis patients and healthy controls (all pc = 1.0). The optimal biomarker combination included AGP, ceruloplasmin, LPGDS and transferrin (area under the curve = 1.0). Conclusions A urinary biomarker panel comprising AGP, ceruloplasmin, LPGDS and transferrin previously validated within UK/US cohorts also performed excellently within a racially distinct South African cohort which displayed more severe lupus nephritis.

Phagocyte-specific S100A8/A9 Protein Levels During Disease Exacerbations and Infections in Systemic Lupus Erythematosus

2009 ◽  
Vol 36 (10) ◽  
pp. 2190-2194 ◽  
Author(s):  
MUHAMMAD S. SOYFOO ◽  
JOHANNES ROTH ◽  
THOMAS VOGL ◽  
ROLAND POCHET ◽  
GUY DECAUX
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Calcium Binding ◽  
Activity Index ◽  
Sandwich Elisa ◽  
Serum Levels ◽  
Healthy Controls ◽  
Systemic Lupus

Objective:S100A8 and S100A9 are calcium binding proteins of the S100 family highly expressed in neutrophils and monocytes. S100 proteins are novel ligands of TLR4 important in modulating inflammation. High levels of S100A8/A9 found in human inflammatory diseases are a marker of disease activity in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). We determined levels of S100A8/A9 in sera of patients with systemic lupus erythematosus (SLE) and analyzed their relation to clinical variables of disease activity.Methods.A group of 93 patients with SLE were studied over a period of 3 years, and 143 serum samples were analyzed. S100A8/A9 serum concentrations were determined by a sandwich ELISA. Sera from 10 primary Sjögren’s syndrome (pSS) patients and 50 healthy volunteers were used as controls. Correlations to SLEDAI, ANA, anti-dsDNA, WBC, CH50, C4, and CRP were made. In addition, infections were recorded in all SLE patients.Results.Serum levels of S100A8/A9 were significantly (p = 0.04) higher in SLE patients (1412 ± 664 ng/ml) versus healthy controls (339 ± 35 ng/ml) and pSS patients (400 ± 85 ng/ml). The only significant correlation (r = 0.219; p = 0.015) was found was between S100A8/A9 and SLEDAI. Further, SLE patients with concomitant infections had higher serum levels of S100A8/A9 (39300 ± 13375 ng/ml) than those without infections (1150 ± 422 ng/ml).Conclusion.Serum levels of S100A8/A9 are significantly raised in SLE versus pSS patients and healthy controls and can be correlated to a disease activity index. S100A8/A9 is a more relevant marker of infection in SLE patients.

scholarly journals Tim-3 associated with apoptotic NK cells and disease activity in SLE

2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Di Zhao ◽  
Xiao Yang ◽  
Jie Zhang ◽  
Yi Zhang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Flow Cytometry ◽  
T Cell ◽  
Disease Activity ◽  
Nk Cells ◽  
Lupus Erythematosus ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Potential Target

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been found to play important roles in systemic lupus erythematosus (SLE), however, whether Tim-3 is involved in apoptosis of NK cells in SLE remains unknown. The proportion of CD3−CD56+ NK cells and the percentage of AnnexinV+ NK cells were analyzed by flow cytometry in SLE patients and healthy controls. Tim-3 expression on NK cells was also evaluated by flow cytometry. We firstly observed a decreased proportion of NK cells and an increased proportion of apoptotic NK cells in SLE patients. The proportion of apoptotic NK cells was positively correlated with anti-dsDNA and SLEDAI. Tim-3 expression on NK cells was up-regulated in SLE patients. Further analysis showed that Tim-3 expression on NK cells was negatively correlated with the proportion of apoptotic NK cells, anti-dsDNA and SLEDAI, while positively correlated with the proportion of NK cells. The present results suggest that Tim-3 might play roles in SLE by regulating the apoptosis of NK cells and Tim-3 might serve as a potential target for the treatment of SLE.

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