Urine β-2-glycoprotein 1 as a biomarker for diagnosis of systemic lupus erythematosus

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Jung Sun Lee ◽  
Eun-Ju Lee ◽  
Jeonghun Yeom ◽  
Ji Seon Oh ◽  
Seokchan Hong ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Medical Center ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Urine Samples ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Lupus ◽  
Asan Medical

Objective The need for a biomarker with robust sensitivity and specificity in diagnosing systemic lupus erythematosus (SLE) remains unmet. Compared with blood samples, urine samples are more easily collected; thus, we aimed to identify such a biomarker based on urinary proteomics which could distinguish patients with SLE from healthy controls (HCs). Methods Urine samples were collected from 76 SLE patients who visited rheumatology clinic in 2019 at Asan medical center and from 25 HCs. Urine proteins were analyzed using sequential windowed acquisition of all theoretical fragment ion spectra-mass spectrometry, and the candidate marker was confirmed by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic curve analysis was used to determine the diagnostic value of the candidate biomarker. Results Of 1157 proteins quantified, 153 were differentially expressed in urine samples from HCs. Among them were previously known markers including α-1-acid glycoprotein 1, α-2-HS-glycoprotein, ceruloplasmin, and prostaglandin-H2 D-isomerase. Moreover, the amount of β-2 glycoprotein (APOH) was increased in the urine of patients with SLE. The ELISA results also showed the level of urine APOH was higher in patients with SLE than in HCs and patients with rheumatoid arthritis. Moreover, the level was not different between SLE patients with and without nephritis. The urine APOH had an area under the curve value of 0.946 at a cut-off value of 228.53 ng/mg (sensitivity 91.5%, specificity 92.0%) for the diagnosis of SLE. Conclusion The results indicate that the urine APOH level can be an appropriate screening tool in a clinical setting when SLE is suspected.

Anti-nucleosome, anti-chromatin, anti-dsDNA and anti-histone antibody reactivity in systemic lupus erythematosus

2004 ◽  
Vol 42 (3) ◽  
Author(s):  
Concepción González ◽  
Belen Garcia-Berrocal ◽  
Oscar Herráez ◽  
José Alejandro Navajo ◽  
José ManuelGonzález-Buitrago
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Blood Donors ◽  
Area Under The Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Likelihood Ratios ◽  
Systemic Lupus ◽  
Dsdna Antibodies

AbstractAnti-nucleosome (anti-chromatin) antibodies play a key role in the pathogenesis of systemic lupus erythematosus (SLE). The objective of the present study was to determine the clinical significance of anti-nucleosome (anti-chromatin) antibodies, anti-dsDNA antibodies and anti-histone antibodies in patients with SLE in relation to patients with positive nuclear antibodies and healthy controls. We measured anti-nucleosome (anti-chromatin) antibodies, anti-dsDNA antibodies and anti-histone antibodies in 70 patients with SLE, 35 antinuclear antibody (ANA)-positive subjects without autoimmune disease and 35 blood donors. All antibodies were determined by enzyme-linked immunosorbent assay (ELISA). We obtained the receiver operating caracteristic (ROC) curve and the area under the curve (AUC) for each autoantibody. Likewise, we obtained the sensitivity, specificity and positive and negative likelihood ratios for each autoantibody. The highest AUC was obtained for anti-nucleosome (0.898) and the lowest AUC for a kit for anti-dsDNA (0.725). Stratification of the control group (ANA-positive subjects without autoimmune disease and blood donors) produced significant changes in the AUCs; all AUCs decreased when ANA-positive patients without autoimmune disease were considered as controls and all AUCs increased when blood donors were considered as controls. These effects were less marked in anti-dsDNA antibodies. We observed discrepancies between kits (anti-nucleosome and anti-chromatin and two for anti-dsDNA). The highest sensitivity for SLE was obtained for anti-nucleosome antibodies (86%) and the highest specificity was obtained for anti-dsDNA antibodies (90%). In conclusion, anti-nucleosome and anti-chromatin kits show different degrees of clinical accuracy due to the cut-off selected by the manufacturer. Once the kits with the best performance and the optimal cut-offs have been selected, anti-nucleosome antibodies and anti-dsDNA antibodies provide similar information in established SLE.

scholarly journals Characterization of the thrombin generation profile in systemic lupus erythematosus

2017 ◽  
Vol 104 (1) ◽  
pp. 35-41 ◽  
Author(s):  
A Kern ◽  
E Barabás ◽  
A Balog ◽  
Sz Burcsár ◽  
M Kiszelák ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Area Under The Curve ◽  
Autoimmune Disorder ◽  
Systemic Lupus ◽  
Time To Peak ◽  
Cat Assay ◽  
Coagulation Tests ◽  
Healthy Control

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.

scholarly journals VP1 DNA sequences of JC and BK viruses detected in urine of systemic lupus erythematosus patients reveal no differences from strains expressed in normal individuals

2000 ◽  
Vol 81 (11) ◽  
pp. 2625-2633 ◽  
Author(s):  
Signy Bendiksen ◽  
Ole Petter Rekvig ◽  
Marijke Van Ghelue ◽  
Ugo Moens
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Pregnant Women ◽  
Dna Sequences ◽  
Lupus Erythematosus ◽  
Urine Samples ◽  
Virus Reactivation ◽  
Systemic Lupus ◽  
Significant Difference ◽  
Multiple Sclerosis Patients ◽  
Urine Specimens

The ubiquitous human polyomaviruses BK (BKV) and JC (JCV) persist with no adverse effects in immunocompetent individuals. Virus-induced pathogenesis has been linked to virus reactivation during impaired immune conditions. Previous studies have shown a significant difference between the VP1 DNA sequences of JCV obtained from control urine samples and those in progressive multifocal leukoencephalopathy brain samples. This difference could not be detected when comparing normal control urinary JCV DNA with DNA sequences from chronic progressive multiple sclerosis patients. Since BKV and JCV are readily activated in systemic lupus erythematosus (SLE) patients, the presence of specific strains, related to VP1 DNA sequences, was investigated in these patients. VP1 DNA sequences in 100 urine samples from 21 SLE patients and 75 urine samples from 75 healthy pregnant women were analysed and compared to previously reported sequences. The results show that the VP1 sequence profiles of JCV and BKV excreted by SLE patients do not differ significantly from those excreted by immunocompetent individuals. The European JCV subtypes 1A or 1B were represented among all JCV-positive urine specimens, while BKV VP1 sequences showed complete, or almost complete, identity with the MM or JL strains. Different urine samples from the same patient collected over a 1 year period were predominantly stable. BKV VP1 DNA in urine specimens from healthy pregnant women was only detected during the third trimester of their pregnancy. These results argue against SLE-specific JCV and BKV strains and suggest reactivation of the viruses rather than recurrent re-infections of patients with SLE.

scholarly journals Lack of Association between Serum Interleukin-23 and Interleukin-27 Levels and Disease Activity in Patients with Active Systemic Lupus Erythematosus

2021 ◽  
Vol 10 (20) ◽  
pp. 4788
Author(s):  
Katarzyna Pawlak-Buś ◽  
Wiktor Schmidt ◽  
Piotr Leszczyński
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Systemic Autoimmune Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Lupus ◽  
Interleukin 27 ◽  
Interleukin 23

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of multiple autoantibodies, resulting in tissue and organ damage. Recent studies have revealed that interleukin-23 (IL-23) and interleukin-27 (IL-27) may be therapeutically relevant in selected SLE manifestations. This study aimed to identify associations between serum IL-27 and IL-23 levels and disease activity in Polish patients with different manifestations of SLE: neuropsychiatric lupus (NPSLE), and lupus nephritis (LN). Associations between interleukin levels and oligo-specific antibodies against double-stranded DNA (dsDNA), dose of glucocorticoids, and type of treatment were also analyzed. An enzyme-linked immunosorbent assay was used to assess anti-dsDNA antibodies and analyze the serum concentration of IL-27 and IL-23 from 72 patients aged 19–74 years with confirmed active SLE. Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2-K). No significant correlations between interleukin levels and SLEDAI score, anti-dsDNA, corticosteroid dose, or type of treatment were noted. Patients with NPSLE and LN presented the highest median scores of SLEDAI.

C-reactive Protein Is a More Sensitive and Specific Marker for Diagnosing Bacterial Infections in Systemic Lupus Erythematosus Compared to S100A8/A9 and Procalcitonin

2012 ◽  
Vol 39 (4) ◽  
pp. 728-734 ◽  
Author(s):  
HYOUN-AH KIM ◽  
JA-YOUNG JEON ◽  
JEONG-MI AN ◽  
BO-RAM KOH ◽  
CHANG-HEE SUH
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Bacterial Infections ◽  
Area Under The Curve ◽  
Specific Marker ◽  
Operating Characteristics ◽  
C Reactive Protein ◽  
Systemic Lupus ◽  
Serum Samples ◽  
Reactive Protein

Objective.C-reactive protein (CRP), S100A8/A9, and procalcitonin have been suggested as markers of infection in patients with systemic lupus erythematosus (SLE). We investigated the clinical significance of these factors for indication of infection in SLE.Methods.Blood samples were prospectively collected from 34 patients with SLE who had bacterial infections and 39 patients with SLE who had disease flares and no evidence of infection. A second set of serum samples was collected after the infections or flares were resolved.Results.CRP levels of SLE patients with infections were higher than those with flares [5.9 mg/dl (IQR 2.42, 10.53) vs 0.06 mg/dl (IQR 0.03, 0.15), p < 0.001] and decreased after the infection was resolved. S100A8/A9 and procalcitonin levels of SLE patients with infection were also higher [4.69 μg/ml (IQR 2.25, 12.07) vs 1.07 (IQR 0.49, 3.05) (p < 0.001) and 0 ng/ml (IQR 0–0.38) vs 0 (0–0) (p < 0.001), respectively]; these levels were also reduced once the infection disappeared. In the receiver-operating characteristics analysis of CRP, S100A8/A9, and procalcitonin, the area under the curve was 0.966 (95% CI 0.925–1.007), 0.732 (95% CI 0.61–0.854), and 0.667 (95% CI 0.534–0.799), respectively. CRP indicated the presence of an infection with a sensitivity of 100% and a specificity of 90%, with a cutoff value of 1.35 mg/dl.Conclusion.Our data suggest that CRP is the most sensitive and specific marker for diagnosing bacterial infections in SLE.

Reduced expression of hematopoietic progenitor kinase 1 in T follicular helper cells causes autoimmunity of systemic lupus erythematosus

Lupus ◽  
2021 ◽  
pp. 096120332110625
Author(s):  
Huilin Zhang ◽  
Yuming Xie ◽  
Junke Huang ◽  
Danhong Luo ◽  
Qing Zhang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Lupus ◽  
Hematopoietic Progenitor ◽  
Protein Levels ◽  
Tfh Cells ◽  
Follicular Helper

Backgroud T follicular helper (Tfh) cells have been discovered to be the main CD4+ T cells assisting B cells to produce antibody. They are over activated in patients with systemic lupus erythematosus (SLE) and consequently lead to excessive immunity. Hematopoietic progenitor kinase 1 (HPK1) negatively regulates T cell-mediated immune responses and TCR signal. This study aimed to investigate the roles of HPK1 in SLE Tfh cells. Methods HPK1 mRNA and protein levels in Tfh cells were measured by real-time quantitative PCR and western blot analysis, respectively. The production of IL-21, B cell−activating factor (BAFF), interferon γ (IFNγ), IL-17A, IgM, IgG1, IgG2, and IgG3 were analyzed using enzyme linked immunosorbent assay. Tfh cells proliferation was evaluated with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results HPK1 mRNA and protein levels were significantly reduced in SLE Tfh cells, and negatively correlated with SLE disease activity index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for SLE (SDI). Knocking down HPK1 with siRNA in normal Tfh cells greatly elevated Tfh cells proliferation and secretions of IL-21, BAFF, IFNγ, IgG1, IgG2, and IgG3. There were no marked alterations in IL-17A and IgM productions. The opposite effects were observed in SLE Tfh cells transfected with HPK1 overexpressing plasmid: Tfh cells proliferation and productions of IL-21, BAFF, IFNγ, IgG1, IgG2, and IgG3 were all alleviated. And there were no significant changes in IL-17A and IgM levels. Conclusion Our results suggest for the first time that inhibited expression of HPK1 in SLE Tfh cells leading to Tfh cells overactivation and B cells overstimulation, subsequently, the onset and progression of SLE.

Anti–α-enolase antibody combined with β2 microglobulin evaluated the incidence of nephritis in systemic lupus erythematosus patients

Lupus ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 365-370 ◽  
Author(s):  
Y Huang ◽  
L Chen ◽  
K Chen ◽  
F Huang ◽  
Y Feng ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Correlation Analysis ◽  
Lupus Erythematosus ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Β2 Microglobulin ◽  
Potential Indicator ◽  
Operating Characteristic Curve

Objective Anti–α-enolase antibody (Ab) combined with β2 microglobulin (β2-MG) were investigated to predict the incidence of nephritis in systemic lupus erythematosus (SLE) patients. Methods Levels of serum anti–α-enolase Ab and urinary β2-MG were detected in 115 SLE patients, 29 SLE patients with nephritis and 70 healthy controls by ELISA and immunoturbidimetry, respectively. Furthermore, the correlation between anti–α-enolase Ab combined with β2-MG and the incidence of nephritis in SLE patients was evaluated by correlation analysis. Results The optical density value of serum anti–α-enolase Ab in SLE patients with nephritis (0.84) was greatly increased compared with SLE patients (0.76) or healthy controls (0.54). Moreover, the levels of urinary β2-MG in SLE patients with nephritis (6.75 mg/L) were increased compared with SLE patients (3.45 mg/L) or healthy controls (1.48 mg/L). There was a positive correlation between the level of anti–α-enolase Ab and β2-MG ( r = 0.754). Furthermore, anti–α-enolase Ab combined with β2-MG for evaluating the incidence of nephritis in SLE patients had the best assessment of the effectiveness (area under the receiver operating characteristic curve (AUC): 92.7%) compared with only anti–α-enolase Ab (AUC: 80.9%) or β2-MG (AUC: 84.5%). Conclusion These data suggested that anti–α-enolase Ab may be a potential indicator for the prediction of nephritis in SLE patients.

scholarly journals Development and Validation of a MicroRNA Panel to Differentiate Between Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus and Controls

2019 ◽  
Vol 47 (2) ◽  
pp. 188-196 ◽  
Author(s):  
Michelle J. Ormseth ◽  
Joseph F. Solus ◽  
Quanhu Sheng ◽  
Fei Ye ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Noncoding Rna ◽  
Characteristic Curve ◽  
Systemic Lupus ◽  
Control Subjects ◽  
Development And Validation ◽  
And Control ◽  
Bioinformatic Approach

Objective.MicroRNA (miRNA) are short noncoding RNA that regulate genes and are both biomarkers and mediators of disease. We used small RNA (sRNA) sequencing and machine learning methodology to develop an miRNA panel to reliably differentiate between rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and control subjects.Methods.Plasma samples from 167 RA and 91 control subjects who frequency-matched for age, race, and sex were used for sRNA sequencing. TIGER was used to analyze miRNA. DESeq2 and random forest analyses were used to identify a prioritized list of miRNA differentially expressed in patients with RA. Prioritized miRNA were validated by quantitative PCR, and lasso and logistic regression were used to select the final panel of 6 miRNA that best differentiated RA from controls. The panel was validated in a separate cohort of 12 SLE, 32 RA, and 32 control subjects. Panel efficacy was assessed by area under the receiver operative characteristic curve (AUC) analyses.Results.The final panel included miR-22-3p, miR-24-3p, miR-96-5p, miR-134-5p, miR-140-3p, and miR-627-5p. The panel differentiated RA from control subjects in discovery (AUC = 0.81) and validation cohorts (AUC = 0.71), seronegative RA (AUC = 0.84), RA remission (AUC = 0.85), and patients with SLE (AUC = 0.80) versus controls. Pathway analysis showed upstream regulators and targets of panel miRNA are associated with pathways implicated in RA pathogenesis.Conclusion.An miRNA panel identified by a bioinformatic approach differentiated between RA or SLE patients and control subjects. The panel may represent an autoimmunity signature, perhaps related to inflammatory arthritis, which is not dependent on active disease or seropositivity.

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