scholarly journals Anti-Double-Stranded DNA Isotypes and Anti-C1q Antibody Improve the Diagnostic Specificity of Systemic Lupus Erythematosus

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yu Jia ◽  
Lingling Zhao ◽  
Chunyan Wang ◽  
Jin Shang ◽  
Yi Miao ◽  
...  

Objectives. We aimed to evaluate the value of immunoglobulin (Ig) G, IgM, and IgA isotypes of anti-double-stranded DNA (anti-dsDNA) and anti-C1q antibody in diagnosing systemic lupus erythematosus (SLE) patients and elucidate their association with disease activity and lupus nephritis. Methods. Blood samples were obtained from 96 SLE patients, 62 other autoimmune disease patients, and 60 healthy blood donors. Anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody were measured by enzyme-linked immunosorbent assay. Disease activity of SLE patients was assessed according to the SLE Disease Activity Index score. Results. When specificity was greater than 90%, the sensitivity of anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody in diagnosing SLE was 75%, 45%, 33%, and 49%, respectively. The prevalence of anti-dsDNA IgG (p=0.002), anti-dsDNA IgA (p=0.028), and anti-C1q antibody (p=0.000) in active cases was significantly higher than those in inactive ones. In addition, the presence of anti-C1q antibody was associated with renal involvement (p=0.032). Anti-dsDNA IgM showed no significant association with disease activity, but it was inversely linked with lupus nephritis (p=0.005). When anti-dsDNA IgG and IgA and anti-C1q were combined to evaluate SLE disease activity, the specificity reached the highest level (90%). When anti-C1q positive was accompanied by anti-dsDNA IgM negative, the specificity of diagnosing lupus nephritis was up to 96%. Conclusions. This study demonstrated the role of anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody alone or combination in diagnosing SLE. Anti-dsDNA IgG and IgA and anti-C1q were shown to be associated with disease activity, while anti-dsDNA IgM and anti-C1q were associated with lupus nephritis. When the related antibodies were combined, the diagnostic specificity was significantly higher.

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Christopher Sjӧwall ◽  
Chelsea Bentow ◽  
Mary Ann Aure ◽  
Michael Mahler

Objective. Anti-double-stranded (ds) DNA and anti-C1q autoantibodies are useful tools in the assessment of disease activity and nephritis in systemic lupus erythematosus (SLE) patients. This study aimed to explore the utility of these antibodies along with anti-Ku antibodies in an oligoparametric model approach for the assessment of disease activity and lupus nephritis. Methods. Samples from 261 well-characterized SLE patients were tested using chemiluminescent immunoassays (CIA) for anti-dsDNA and anti-Ku antibodies as well as by anti-C1q antibody ELISA (Inova Diagnostics, USA). Of these SLE patients, 26.4% had lupus nephritis (LN) at the time of blood draw or had a history of LN, and modified SLE disease activity index-2K (SLEDAI) scores were used to assess disease activity. Results. All three antibodies demonstrated higher prevalence and higher antibody levels in active versus inactive SLE patients and in LN versus non-LN patients. When oligoparametric analysis was performed, the likelihood of LN and patients with active disease increased with dual and triple positivity. Conclusions. Anti-dsDNA and anti-C1q antibodies are useful tools to identify disease activity and/or renal involvement in SLE patients. In addition, the combination of those antibodies in a two-parametric score might improve the clinical utility of those markers.


2021 ◽  
Vol 10 (20) ◽  
pp. 4788
Author(s):  
Katarzyna Pawlak-Buś ◽  
Wiktor Schmidt ◽  
Piotr Leszczyński

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.


Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
Author(s):  
Z Rezaieyazdi ◽  
M Sahebari ◽  
MR Hatef ◽  
B Abbasi ◽  
H Rafatpanah ◽  
...  

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.


Author(s):  
Sonia L La’ulu ◽  
Brenda B Suh-Lailam ◽  
K Wayne Davis ◽  
Joely A Straseski ◽  
Anne E Tebo

Background Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. This study evaluates the prevalence and correlation between neutrophil gelatinase-associated lipocalin and other biomarkers associated with renal involvement in systemic lupus erythematosus. Methods Paired serum and urine specimens from 50 suspected systemic lupus erythematosus patients, characterized by antinuclear antibodies detected by indirect immunofluorescence assay and varying positive concentrations of anti-double stranded DNA antibodies by Crithidia luciliae immunofluorescence assay, were investigated. Of these 50 patients, 18 were identified with renal involvement based upon laboratory serology. Patients and healthy control serum samples ( n = 50) were also evaluated for high avidity double stranded DNA IgG antibodies, anti-C1q IgG antibodies, and serum creatinine. The prevalence and relationship between biomarkers were evaluated using statistical methods. Results Serum and urine neutrophil gelatinase-associated lipocalin concentrations were significantly elevated in patients compared to controls, with a prevalence of 24% and 36%, respectively. These concentrations were also more markedly increased in systemic lupus erythematosus patients with renal involvement than those without. Spearman’s correlations between neutrophil gelatinase-associated lipocalin and other biomarkers tested ranged from 0.06 to 0.66 in all patients. Combined concordance as determined by Cronbach alpha coefficient between biomarkers was reduced from 0.71 to 0.58 (serum) and 0.62 (urine) when neutrophil gelatinase-associated lipocalin was removed. Conclusions Neutrophil gelatinase-associated lipocalin concentrations are elevated and demonstrate variable associated with other laboratory markers for renal involvement in systemic lupus erythematosus. Prospective longitudinal studies are needed to determine the optimal biomarker combinations for use in routine management of systemic lupus erythematosus patients at-risk for lupus nephritis.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
M Enrica ◽  
A Tjandrawati ◽  
S Rachmayati ◽  
Laniyati Hamijoyo

Background: Lupus nephritis is defined as renal involvement in systemic lupus erythematosus (SLE) patients and the most important cause of morbidity and mortality. The diagnostic criteria that used to diagnose lupus nephritis are 1997 American Collegeof Rheumatology is 24 hours urine protein ≥500 mg and/or cellular cast, but significant renal damage can occur without proteinuria or cellular cast. Anti-C1q is an autoantibody that is produced by a chronic alteration of C1q collagen domain. Anti-C1q is a new specific marker for renal marker.Objective: To determine the validity of anti-C1q serum by using 1997 American College of Rheumatology criteria as a gold standard. Methods: This is a cross sectional study, conducted in October to December 2014 at Hasan Sadikin Hospital Bandung. The subjects had systemic lupus erythematosus with and without renal involvement, based on 1997 American College of Rheumatology criteria for SLE.Results: There were 65 subjects included in this study, 64 subjects were female and 1 subject was male. The age average was 32 (SD 11.7) years old. As many as 66.2% subjects had been diagnosed with lupus erythematosus systemic at least 3 years. Twenty four hours urine protein was measured using spectrophotometry, urine sediment was examinedfor cellular cast, and anti-C1q serum was measured using micro enzyme linked immunosorbent assay. Based on American College of Rheumatology criteria, 34 subjects were classified as lupus nephritis group while 31 subjects were classified as non-lupus nephritis group. The area under the curve of anti-C1q was 0.610. The cut-off value used in this study was 10.43 U/ml. The sensitivity, specificity, positive predictive value,negative predictive value and accuracy of anti-C1q assay were 41.18%, 77.42%, 66.67%, 54.55% and 58.46% respectively.Conclusion: Anti-C1q assay, based on this study, hasa low sensitivity and medium specificity to detect lupusnephritis


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Azita Sohrabian ◽  
Ioannis Parodis ◽  
Nellie Carlströmer-Berthén ◽  
Martina Frodlund ◽  
Andreas Jönsen ◽  
...  

Abstract Introduction Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value. Methods A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment. Results High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers. Conclusion Immune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.


Lupus ◽  
2018 ◽  
Vol 28 (1) ◽  
pp. 34-43 ◽  
Author(s):  
L. Pacheco-Lugo ◽  
J. Sáenz-García ◽  
E Navarro Quiroz ◽  
H. González Torres ◽  
L. Fang ◽  
...  

Background Systemic lupus erythematosus is a heterogeneous chronic inflammatory autoimmune disorder characterized by an exacerbated expression of cytokines and chemokines in different tissues and organs. Renal involvement is a significant contributor to the morbidity and mortality of systemic lupus erythematosus, and its diagnosis is based on renal biopsy, an invasive procedure with a high risk of complications. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with systemic lupus erythematosus is a priority. Aim To evaluate the plasma levels of a panel of cytokines and chemokines using multiplex xMAP technology in a cohort of Colombian patients with active and inactive systemic lupus erythematosus, and to evaluate their potential as biomarkers of renal involvement. Results Plasma from 40 systemic lupus erythematosus non-nephritis patients and 80 lupus nephritis patients with different levels of renal involvement were analyzed for 39 cytokines using Luminex xMAP technology. Lupus nephritis patients had significantly increased plasma eotaxin, TNF-α, interleukin-17-α, interleukin-10, and interleukin-15 as compared to the systemic lupus erythematosus non-nephritis group. Macrophage-derived chemokine, growth regulated oncogene alpha, and epidermal growth factor were significantly elevated in systemic lupus erythematosus non-nephritis patients when compared to lupus nephritis individuals. Plasma eotaxin levels allowed a discrimination between systemic lupus erythematosus non-nephritis and lupus nephritis patients, for which we performed a receiver operating characteristic curve to confirm. We observed a correlation of eotaxin levels with active nephritis (Systemic Lupus Erythematosus Disease Activity Index). Our data indicate that circulating cytokines and chemokines could be considered good predictors of renal involvement in individuals with systemic lupus erythematosus.


2005 ◽  
Vol 12 (1) ◽  
pp. 56-59 ◽  
Author(s):  
Krisztina Sallai ◽  
Eszter Nagy ◽  
Beata Derfalvy ◽  
Györgyi Müzes ◽  
Peter Gergely

ABSTRACT Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75% ± 12.1%) than in the controls (81.3% ± 9.25%) (P < 0.001). DNase activity in patients with UCTD (64.9% ± 18.2%; P = 0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3 ± 851) than the controls (1.44 ± 2.77; P < 0.01) or UCTD patients (39.9 ± 57.7; P < 0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement.


2021 ◽  
Vol 12 ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  

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.


2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Ting Zhang ◽  
Yong Du ◽  
Qingqing Wu ◽  
Hao Li ◽  
Thao Nguyen ◽  
...  

Abstract Objectives To assay salivary anti-nuclear antibody (ANA) and its isotypes in patients with systemic lupus erythematosus (SLE) and to investigate relevant clinical associations. Methods Saliva samples were collected from SLE patients and assayed for salivary ANA using immunofluorescence (IF). Isotypes of salivary ANA, including IgG-ANA, IgA-ANA, and IgM-ANA, were quantified using enzyme-linked immunosorbent assay. The correlations between clinical parameters and levels of salivary ANA and isotypes were evaluated. Results Salivary ANA IF intensities were significantly higher in SLE patients than in healthy controls, irrespective of SLE patient disease activity, and strongly correlated with serum ANA titers. Salivary ANA was detected in 67.14% of SLE patients and 10.00% of healthy controls (p < 0.001). Among ANA-positive samples, 80.85% exhibited a nuclear ANA pattern, and 42.55% exhibited a cytoplasmic ANA pattern. Salivary IgG-ANA, IgA-ANA, and IgM-ANA levels, as assayed by ELISA, were significantly increased in both active and less active SLE patients compared with healthy controls, and levels of each isotype were significantly correlated with serum ANA titer. Salivary IgM-ANA levels correlated with the physician global assessment (PGA), SLE disease activity index (SLEDAI), and negatively with serum C3 and C4. Salivary IgG-ANA also correlated with erythrocyte sedimentation rate (ESR), SLEDAI, and negatively with serum C3. Conclusion Salivary ANA levels correlate with serum ANA titer, and salivary IgM-ANA and IgG-ANA correlate variably with PGA, SLEDAI, ESR and complement levels. These findings underscore the potential of using salivary ANA and ANA isotypes as surrogates for serum ANA, particularly for future point-of-care applications since saliva is easier to obtain than blood.


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