scholarly journals Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

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.

Lupus ◽  
2019 ◽  
Vol 28 (7) ◽  
pp. 826-833 ◽  
Author(s):  
R Wakiya ◽  
T Kameda ◽  
K Ueeda ◽  
S Nakashima ◽  
H Shimada ◽  
...  

Objectives We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. Methods SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. Results S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with ( n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement ( n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. Conclusion HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.


2012 ◽  
Vol 40 (3) ◽  
pp. 265-272 ◽  
Author(s):  
ANNA ABOU-RAYA ◽  
SUZAN ABOU-RAYA ◽  
MADIHAH HELMII

Objective.Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory autoimmune disease. Vitamin D has potent immunomodulatory properties that support its use in the treatment of autoimmune conditions, including SLE. We assessed vitamin D status in patients with SLE and determined alterations in inflammatory and hemostatic markers and disease activity before and after vitamin D supplementation.Methods.Patients with SLE (n = 267) were randomized 2:1 to receive either oral cholecalciferol 2000 IU/day or placebo for 12 months. Outcome measures included assessment of alterations in levels of proinflammatory cytokines and hemostatic markers, and improvement in disease activity before and after 12 months of supplementation. Disease activity was measured by the SLE Disease Activity Index. Vitamin D levels were measured by Liaison immunoassay (normal 30–100 ng/ml). Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels < 10 ng/ml as vitamin D deficiency.Results.The mean 25(OH)D level at baseline was 19.8 ng/ml in patients compared to 28.7 ng/ml in controls. The overall prevalence of suboptimal and deficient 25(OH)D serum levels among patients with SLE at baseline was 69% and 39%, respectively. Lower 25(OH)D levels correlated significantly with higher SLE disease activity. At 12 months of therapy, there was a significant improvement in levels of inflammatory and hemostatic markers as well as disease activity in the treatment group compared to the placebo group.Conclusion.Vitamin D supplementation in patients with SLE is recommended because increased vitamin D levels seem to ameliorate inflammatory and hemostatic markers and show a tendency toward subsequent clinical improvement. Clinical Trial Registry NCT01425775.


Lupus ◽  
2016 ◽  
Vol 26 (2) ◽  
pp. 139-149 ◽  
Author(s):  
H Tydén ◽  
C Lood ◽  
B Gullstrand ◽  
A Jönsen ◽  
F Ivars ◽  
...  

Objectives Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs. Methods Serum levels of S100A8/A9 and S100A12 were measured by ELISA in paired samples of 100 SLE patients at time points of higher and lower disease activity. Serum-mediated phagocytosis of NCs by PMNs was analysed by flow cytometry. Clinical data were recorded at time points of blood sampling. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with high disease activity compared to paired samples at low disease activity ( p = 0.01 and p = 0.008, respectively). Elevated levels of S100A8/A9 were particularly seen in patients with anti-dsDNA antibodies ( p = 0.01) and glomerulonephritis before treatment ( p = 0.02). Immunosuppressive therapy was associated with a reduction of S100A8/A9 serum levels ( p = 0.002). The ability of serum to support phagocytosis of NCs by PMNs was related to increased S100A8/A9 levels ( p = 0.01). Conclusions Elevated serum levels of S100A8/A9 may be used to monitor disease activity and response to treatment in SLE patients, especially in patients with glomerulonephritis. S100A12 may be a marker of disease activity in SLE. Increased S100A8/A9 levels may reflect immune-pathological processes involving phagocytosis of immune complexes by PMNs.


Lupus ◽  
2020 ◽  
Vol 29 (7) ◽  
pp. 686-696
Author(s):  
Shinya Hirahara ◽  
Yasuhiro Katsumata ◽  
Hidenaga Kawasumi ◽  
Yashushi Kawaguchi ◽  
Masayoshi Harigai

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.


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 8 (3) ◽  
pp. 204-210
Author(s):  
Mohammadreza Nakhjavani ◽  
Sima Abediazar ◽  
Amir Ghorbanihaghjo ◽  
Niloofar Esmaeili ◽  
Tala Pourlak ◽  
...  

Introduction: Lupus nephritis (LN) is one of the most severe signs of systemic lupus erythematosus (SLE) and rapid diagnosis of kidney damage remains an important concern for LN. Objectives: The aim of this study was to investigate the association of the serum levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and interleukin 17 (IL-17) with SLE severity, renal involvement, and other clinical manifestations in lupus patients. Patients and Methods: In order to determine a better biomarker for the detection of renal damage, this study evaluated the ability of serum TWEAK (sTWEAK) and IL-17 in lupus patients with (n=25) and without (n=25) nephritis and healthy controls (n=39). Moreover, it compared the levels of these cytokines with disease activity and chronicity as well as traditional serum markers including complement C3 and C4, creatinine, and proteinuria in lupus patients. Results: Increased levels of sTWEAK and IL-17 were observed in SLE and LN groups compared to healthy controls and non-LN groups, respectively. Significant positive associations were observed between serum TWEAK and IL-17 levels and systemic lupus erythematosus disease activity index (SLEDAI), proteinuria, nephritis activity index, and some clinical manifestations (P<0.05). Discriminating the ability of the studied cytokines were not better than the utility of any markers individually. Conclusion: The serum levels of TWEAK and IL-17 in the SLE and LN groups were significantly higher than the control group and both markers were indicative of the renal disease severity; therefore, they could possibly indicate renal involvement in the lupus patients.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 588.2-588
Author(s):  
G. Olivieri ◽  
F. Ceccarelli ◽  
F. Natalucci ◽  
F. R. Spinelli ◽  
C. Alessandri ◽  
...  

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p< 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.References:[1]Fanouriakis A et al. Ann Rheum Dis. 2019 Jun;78(6):736-745.Disclosure of Interests:None declared


Lupus ◽  
2017 ◽  
Vol 26 (13) ◽  
pp. 1448-1456 ◽  
Author(s):  
K C Maloney ◽  
T S Ferguson ◽  
H D Stewart ◽  
A A Myers ◽  
K De Ceulaer

Background Epidemiological studies in systemic lupus erythematosus have been reported in the literature in many countries and ethnic groups. Although systemic lupus erythematosus in Jamaica has been described in the past, there has not been a detailed evaluation of systemic lupus erythematosus patients in urban Jamaica, a largely Afro-Caribbean population. The goal of this study was to describe the clinical features, particularly disease activity, damage index and immunological features, of 150 systemic lupus erythematosus subjects. Methods 150 adult patients (≥18 years) followed in rheumatology clinic at a tertiary rheumatology hospital centre (one of two of the major public referral centres in Jamaica) and the private rheumatology offices in urban Jamaica who fulfilled Systemic Lupus International Collaborating Clinics (SLICC) criteria were included. Data were collected by detailed clinical interview and examination and laboratory investigations. Hence demographics, SLICC criteria, immunological profile, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and SLICC/American College of Rheumatology (ACR) damage index (SDI) were documented. Results Of the 150 patients, 145 (96.7%) were female and five (3.3%) were male. The mean age at systemic lupus erythematosus onset was 33.2 ± 10.9. Mean disease duration was 11.3 ± 8.6 years. The most prevalent clinical SLICC criteria were musculoskeletal, with 141 (94%) of subjects experiencing arthralgia/arthritis, followed by mucocutaneous manifestations of alopecia 103 (68.7%) and malar rash 46 (30.7%), discoid rash 45 (30%) and photosensitivity 40 (26.7%). Lupus nephritis (biopsy proven) occurred in 42 (28%) subjects and 25 (16.7%) met SLICC diagnostic criteria with only positive antinuclear antibodies/dsDNA antibodies and lupus nephritis on renal biopsy. The most common laboratory SLICC criteria were positive antinuclear antibodies 136 (90.7%) followed by anti-dsDNA antibodies 95 (63.3%) and low complement (C3) levels 38 (25.3%). Twenty-seven (18%) met SLICC diagnostic criteria with only positive antinuclear antibodies/anti-dsDNA antibodies and lupus nephritis on renal biopsy. Mean SLEDAI score was 6.9 ± 5.1 with a range of 0–32. Organ damage occurred in 129 (86%) patients; mean SDI was 2.4 ± 1.8, with a range of 0–9. Conclusion These results are similar to the clinical manifestations reported in other Afro-Caribbean populations; however, distinct differences exist with respect to organ involvement and damage, particularly with respect to renal involvement, which appears to be reduced in our participants.


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