scholarly journals Associations of the Levels of C4d-bearing Reticulocytes and High-avidity Anti-dsDNA Antibodies with Disease Activity in Systemic Lupus Erythematosus

2016 ◽  
Vol 43 (9) ◽  
pp. 1657-1664 ◽  
Author(s):  
Claudia Mora ◽  
Jorge Medina-Rosas ◽  
Ana Maria Santos ◽  
Diego A. Jaimes ◽  
Ana M. Arbeláez ◽  
...  

Objective.There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales.Methods.All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured.Results.Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains.Conclusion.R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.

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 ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1074-1081 ◽  
Author(s):  
I Cavazzana ◽  
R Kumar ◽  
C Pozzari ◽  
R Ottaviani ◽  
M Fredi ◽  
...  

Objective The objective of this study was to analyse autoantibodies’ titres modulation during belimumab treatment in 50 patients with systemic lupus erythematosus (SLE). Methods Sera were collected at belimumab start (T0) and every six months until the 24th month. Disease activity index (SLEDAI-2K) was analysed at every timepoint. High avidity anti-dsDNA was detected by radioimmunological method, anti-ENA, anti-cardiolipin antibodies (aCL), anti-β2 glycoprotein I (anti-β2GPI) were analysed by ELISA. Results Fifty patients with SLE (mean SLEDAI-2K: 7.18 ± :3), mean age of 39 ± 11 years and mean follow-up of 13 ± 7.8 years were enrolled. A significant decrease of anti-dsDNA and anti-β2GPI IgM titres was observed at all timepoints. IgG aCL titre showed significant decrease only at T18. Anti-dsDNA negativization was detected in 21%, anti-β2GPI IgG in 33% and aCL IgG in 30% of sera, mostly at T6. Anti-ribosomal showed a significant titre decrease at T6 and T12, with negative seroconversion at T18. Anti-Sm titre significantly dropped down at T6, then remained stable during the time. Significant correlations were found between anti-dsDNA and anti-ribosomal titre and between SLEDAI ratio (SLEDAI value/SLEDAI T0) and anti-ribosomal titre ratio (value/value T0). Conclusions Belimumab treatment induced a significant reduction of SLE-specific autoantibodies titre and IgM anti-β2GPI. Anti-ribosomal titre decrease correlates with anti-dsDNA titre and disease activity improvement.


2021 ◽  
pp. jim-2021-001887
Author(s):  
María Correa-Rodríguez ◽  
Gabriela Pocovi-Gerardino ◽  
Jose Luis Callejas-Rubio ◽  
Raquel Ríos-Fernández ◽  
María Martín-Amada ◽  
...  

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the formation of antigen–antibody complexes which trigger an immune response. We investigate certain autoantibodies including nucleosome, double-stranded DNA (dsDNA), Smith, ribonucleoprotein, and Sjögren’s syndrome-related antigens, and examine their associations with disease activity, damage accrual, and SLE-related clinical and serological manifestations in patients with SLE. We conducted a cross-sectional study with a total 293 patients (90.4% female, mean age 46.87±12.94 years) and used the Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) to evaluate disease activity and disease-related damage, respectively. Systemic Lupus Erythematosus Disease Activity Index scores were significantly higher in anti-nucleosome-positive (3.87±2.72 vs 2.52±2.76, p=0.004) and anti-dsDNA-positive (3.08±2.91 vs 2.04±2.48, p=0.010) patients compared with patients without these antibodies. SDI scores were also significantly higher in anti-nucleosome-positive patients (1.61±1.99 vs 0.89±1.06, p=0.004). The presence of antinucleosome (p=0.019) and anti-dsDNA antibodies (p=0.001) both correlated significantly with the incidence of nephritis; anti-La antibodies were associated with arthritis (p=0.022), and we also observed a relationship between the presence of antinucleosome antibodies and leukopenia (p=0.011). Patients with antinucleosome or anti-dsDNA antibodies had a higher disease activity and were likely to have nephritis. Antinucleosome was also associated with more damage accrual. A greater understanding of these autoantibodies could lead to the development of new approaches to more accurate assessments of SLE.


Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Priscila B. S. Medeiros ◽  
Roberta G. Salomão ◽  
Sara R. Teixeira ◽  
Diane M. Rassi ◽  
Luciana Rodrigues ◽  
...  

Abstract Background Systemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT. Methods Cross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression. Results Twenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables. Conclusion Subclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.


2021 ◽  
Vol 10 (10) ◽  
pp. 2137
Author(s):  
Ning-Sheng Lai ◽  
Ming-Chi Lu ◽  
Hsiu-Hua Chang ◽  
Hui-Chin Lo ◽  
Chia-Wen Hsu ◽  
...  

Background and Aim: The aim of this study was to compare the correlation of a recently developed systemic lupus erythematosus disease activity score (SLE-DAS) with the SLE disease activity index 2000 (SLEDAI-2K) with the Lupus Quality of Life questionnaire (LupusQoL) in Taiwanese patients with SLE. Methods: A cross-sectional study was conducted in a regional teaching hospital in Taiwan from April to August 2019. Adult patients with a clinician-confirmed diagnosis of SLE based on the 1997 American College of Rheumatology revised criteria or the 2012 Systemic Lupus International Collaborating Clinics Classification Criteria were recruited. SLE disease activity was measured with both SLEDAI-2K and SLE-DAS. Disease-specific quality of life was assessed using the LupusQoL. Results: Of the 333 patients with SLE in this study, 90.4% were female and 40% were between the ages of 20 and 39 years. The median SLEDAI-2K score was 4.00 (interquartile range [IQR] 2.00–7.50) and the median SLE-DAS score was 2.08 (IQR 1.12–8.24) in our patients with SLE. After adjusting for sex and age intervals, both SLEDAI-2k and SLE-DAS were significantly and inversely associated with all eight domains of LupusQoL. The magnitudes of the mean absolute error, root mean square error, Akaike Information Criterion, Bayesian Information Criterion, and coefficient of determination were comparable between SLEDAI-2K and SLE-DAS. Conclusions: There were no clear differences in the use of SLE-DAS over SLEDAI-2K in assessing HRQoL in patients with SLE. We suggest that, in this aspect, both SLEDAI-2K and SLE-DAS are effective tools for measuring disease activity in patients with SLE.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Conti Fabrizio ◽  
Ceccarelli Fulvia ◽  
Perricone Carlo ◽  
Massaro Laura ◽  
Marocchi Elisa ◽  
...  

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.


2011 ◽  
Vol 38 (11) ◽  
pp. 2395-2399 ◽  
Author(s):  
ZAHI TOUMA ◽  
DAFNA D. GLADMAN ◽  
DOMINIQUE IBAÑEZ ◽  
SHAHRZAD TAGHAVI-ZADEH ◽  
MURRAY B. UROWITZ

Objective.To evaluate the performance of the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable index of disease activity improvement. Also, to determine whether the SRI-50 will enhance the ability of SRI in detecting responders.Methods.Our study was conducted on patients who attended the Lupus Clinic from September 2009 to September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group measure, and the Physician’s Global Assessment were determined initially and at followup. SRI was determined at the followup visit according to its original definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50.Results.A total of 117 patients with SLEDAI-2K ≥ 4 at baseline were studied. Patients had 1 followup visit over a 3-month period. Twenty-nine percent of patients met the original definition of SRI and 35% of patients met the definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50 allowed determination of significant improvement in 7 additional patients. This improvement could not be discerned with the use of SLEDAI-2K as a component of SRI. At followup visits that showed improvement, SRI-50 scores decreased to a greater extent than SLEDAI-2K scores (p < 0.0001).Conclusion.SRI-50 enhances the ability of SRI to identify patients with clinically important improvement in disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical improvement, ≥ 50%, between visits. These properties of the SRI-50 enable it to be used as an independent outcome measure of improvement or as a component of SRI in clinical trials.


2010 ◽  
Vol 38 (1) ◽  
pp. 60-63 ◽  
Author(s):  
DOMINIQUE IBAÑEZ ◽  
DAFNA D. GLADMAN ◽  
ZAHI TOUMA ◽  
MANDANA NIKPOUR ◽  
MURRAY B. UROWITZ

Objective.Adjusted mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; AMS) measures lupus disease activity over time. Our aim was to determine optimal visit frequency for calculating AMS.Methods.Patients followed monthly for 12 consecutive visits were included. AMS was calculated using all of the SLEDAI 2000 (AMSGOLD using all 12 visits), only quarterly visits (AMS3, using visits 3 months apart), semiannual visits (AMS6, using first, middle, and last visits only), and annual visits (AMS12, using only the first and last visits). Comparisons of AMS3, AMS6, and AMS12 with AMSGOLD are made using descriptive statistics.Results.Seventy-eight patients were included (92% women, mean age at SLE diagnosis 30.1 yrs and at study start 46.2 yrs). The mean (SD) AMSGOLD for the entire year was 2.05 (1.66), for AMS3 1.99 (1.65), for AMS6 2.12 (1.87), and for AMS12 2.08 (1.83). Mean (SD) of the absolute differences with AMSGOLD: for AMS3 0.29 (0.33), for AMS6 0.45 (0.59), and for AMS12 0.61 (0.58). Differences that were < 0.5 were considered minimal while those ≥ 1 were deemed important. Comparing AMSGOLD to AMS3, 82% of the differences were minimal and 3% were important. When comparing to AMS6, 68% were minimal and 10% were important, while comparing to AMS12, 50% were minimal and 21% were important.Conclusion.Usual clinic visits occurring quarterly offer a good estimation of disease activity over a 1-year period and are preferred over semiannual and annual visits.


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