Diagnosed SLE Patients Research Articles

The Association of Urinary MCP-1 with Disease Activity of Lupus Nephritis

Background: The association of urinary MCP-1 (Monocyte Chemoattractant Protein-1) with disease activity in lupus nephritis (LN) has been a subject of significant interest. MCP-1 is a chemokine involved in the recruitment and activation of monocytes, which play a critical role in the pathogenesis of LN. Objective: To assess association of Urinary MCP-1 with disease activity of lupus nephritis. Method: This cross sectional study was conducted in the Department of Nephrology, Dhaka Medical College Hospital, Dhaka from January, 2017 to June, 2018. This cross sectional study was performed on 60 biopsy proven lupus nephritis patients and 30 age and sex matched apparently healthy control subjects. All the patients were recruited as per inclusion and exclusion criteria. Diagnosed SLE patients who had renal involvement and undergone renal biopsy for standard clinical indications were recruited by purposive sampling and divided into two groups of active and inactive LN as per operational definition. Results: During the study, The urinary MCP-1 was higher in active LN patients compared to the inactive group and both were higher than the level in the control. Plus, highest Sensitivity and specificity of uMCP-1 observed at cutoff value 433 pg/ml, where sensitivity was 0.967 and specificity was 0.900. Among 30 active lupus nephritis cases raised uMCP-1 was found in 29 cases and among 30 inactive lupus nephritis cases raised uMCP-1 was found in 3 cases. uMCP-1 showed very good agreement in diagnosis of lupus nephritis activity according to Kappa statistics. uMCP-1 in diagnosis of lupus nephritis activity showed accuracy, sensitivity, specificity, PPV and NPV were 0.933, 0.967, 0.900, 0.906 and 0.964 respectively. Conclusion: In conclusion, urinary MCP-1 holds great promise as a useful biomarker for the determination of lupus nephritis activity. Its association with disease activity, predictive value for treatment response and renal outcomes, and non-invasive nature make it an ...

Visual field defect due to Hydroxychloroquine in systemic lupus erythematosus

Abstract Background Hydroxychloroquine (HCQ) is used in the management of a variety of autoimmune disorders, with well-established role in dermatology and rheumatology. However, Hydroxychloroquine and chloroquine (CQ) have been associated with irreversible visual loss due to retinal toxicity. Aim of the Work screening for field affection resulting from HCQ therapy in patients with SLE and assessing the diagnostic accuracy of the investigational methods employed. Subjects and Methods This is a cross-sectional controlled study that was carried out on 90 subjects (<18 years old). It included 45 physician diagnosed SLE patients taking HCQ for more than 1 year. A 45 age-matched healthy subjects were enrolled as a control group. Visual field assessment was performed by Central 10-2 visual field testing using automated Humphery perimetry. Results In comparison to the normal field in the control group, 13 out of 45 (29%) of the patients treated with HCQ had visual field defects most commonly in the central/paracentral area in-spite of no complaint. Conclusion HCQ can affect the visual field and this was not related to the cumulative dose of the drug. Regular field assessment should be done for patients on regular HCQ treatment.

The citrullinated/native index of autoantibodies against hnRNP-DL predicts an individual \u201cwindow of treatment success\u201d in RA patients

BackgroundThere is a need for biomarker to identify patients “at risk” for rheumatoid arthritis (risk-RA) and to better predict the therapeutic response and in this study we tested the hypothesis that novel native and citrullinated heterogeneous nuclear ribonucleoprotein (hnRNP)-DL autoantibodies could be possible biomarkers.MethodsUsing protein macroarray and ELISA, epitope recognition against hnRNP-DL was analysed in sera from different developed RA disease and diagnosed SLE patients. Toll-like receptor (TLR) 7/9 and myeloid differentiation primary response gene 88 (MyD88)-dependency were studied in sera from murine disease models. HnRNP-DL expression in cultivated cells and synovial tissue was analysed by indirect immunofluorescence, immunoblot and immunohistochemistry.ResultsHnRNP-DL was highly expressed in stress granules, citrullinated in the rheumatoid joint and targeted by autoantibodies either as native or citrullinated proteins in patient subsets with different developed RA disease. Structural citrullination dependent epitopes (SCEs) of hnRNP-DL were detected in 58% of the SLE patients although 98% of these sera were α-CCP-2-negative. To obtain a specific citrullinated signal value, we subtracted the native antibody value from the citrullinated signal. The citrullinated/native index of autoantibodies against hnRNP-DL (CNDL-Index) was identified as a new value for an “individual window of treatment success” in early RA and for the detection of RF IgM/α-CCP-2 seronegative RA patients (24–46%). Negative CNDL-index was found in SLE patients, risk-RA and early RA cohorts such as EIRA where the majority of these patients are DAS28-responders to methotrexate (MTX) treatment (87%). High positive CNDL-values were associated with more severe RA, shared epitope and parenchymal changes in the lung. Specifically, native α-hnRNP-DL is TLR7/9-dependent, associated with pain and ROC analysis revealed an association to initial MTX or etanercept treatment response, especially in seronegative RA patients.ConclusionCNDL-index defines people at risk to develop RA and the “window of treatment success” thereby closing the sensitivity gap in RA.

Hydroxychloroquine might reduce risk of incident endometriosis in patients with systemic lupus erythematosus: A retrospective population-based cohort study

SLE, which is common in women, is commonly treated with HCQ, an anti-inflammation medication. Reproductive-age women with SLE are prone to be impacted by endometriosis. This study analyzes the relationship between HCQ and endometriosis patients with SLE in order to determine whether HCQ is effective for treating the latter. This population-based, retrospective cohort study analyzed the SLE risk in a cohort of newly diagnosed SLE patients with endometriosis during 2000 through 2013. Controls were selected at a 1:2 ratio through age-matching using the greedy algorithm. The Cox proportional hazard model was used to analyze the association between HCQ use and endometriosis incidence. Four different Cox regression models were used. Lastly, sensitivity analysis with PSOW and IPW was implemented to evaluate the hazard ratio (HR) of endometriosis after exposure with HCQ. In the cohort where age and sex matched high and low HCQ dosage, the average follow-up time was about 1 year. The cohort's overall incidence rates of endometriosis were 44.54 and 90.03 per 100000 person-month for high and low dosage respectively. The high dose group's conditional hazard ratio (aHR) for incidental endometriosis was 0.482 (CI = 0.191 to 1.213). The incidence rate and Kaplan-Meir curves of endometriosis were consistent with the results for the cohort. This study demonstrated that SLE patients continuously treated with HCQ have a lower risk of developing endometriosis. Clinically, HCQ can be beneficial for endometriosis patients with SLE.

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

BackgroundSystemic 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.ResultsDKK-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.ConclusionDKK-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.

Longitudinal changes in cerebral white matter microstructure in newly diagnosed systemic lupus erythematosus patients

ObjectivesTo evaluate longitudinal variations in diffusion tensor imaging (DTI) metrics of different white matter (WM) tracts of newly diagnosed SLE patients, and to assess whether DTI changes relate to changes in clinical characteristics over time.MethodsA total of 17 newly diagnosed SLE patients (19–55 years) were assessed within 24 months from diagnosis with brain MRI (1.5 T Philips Achieva) at baseline, and after at least 12 months. Fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity values were calculated in several normal-appearing WM tracts. Longitudinal variations in DTI metrics were analysed by repeated measures analysis of variance. DTI changes were separately assessed for 21 WM tracts. Associations between longitudinal alterations of DTI metrics and clinical variables (SLEDAI-2K, complement levels, glucocorticoid dosage) were evaluated using adjusted Spearman correlation analysis.ResultsMean MD and RD values from the normal-appearing WM significantly increased over time (P = 0.019 and P = 0.021, respectively). A significant increase in RD (P = 0.005) and MD (P = 0.012) was found in the left posterior limb of the internal capsule; RD significantly increased in the left retro-lenticular part of the internal capsule (P = 0.013), and fractional anisotropy significantly decreased in the left corticospinal tract (P = 0.029). No significant correlation was found between the longitudinal change in DTI metrics and the change in clinical measures.ConclusionIncrease in diffusivity, reflecting a compromised WM tissue microstructure, starts in initial phases of the SLE disease course, even in the absence of overt neuropsychiatric (NP) symptoms. These results indicate the importance of monitoring NP involvement in SLE, even shortly after diagnosis.

Impact of IL-34, IFN-α and IFN-λ1 on activity of systemic lupus erythematosus in Egyptian patients.

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune, multi-system inflammatory disease. Among cytokines involved in SLE pathogenesis, interferons (particularly IFN-α) and interleukin 34 play a pivotal role. Interestingly, the gene signatures of type III (IFN-λ1) and type I IFNs may overlap. Increased levels of IFN-λ also have been reported in SLE.Objectives: The aim of this study was to assess serum levels of IL-34, IFN-λ1, IFN-α and the relationship between these cytokines and clinical and laboratory parameters and response to treatment in a cohort of Egyptian SLE patients.Material and methodsThe study included 82 newly diagnosed SLE patients: male 17.1% (n = 14), female 82.9% (n = 68), mean age ±SD: 48.6 ±8.2 and 60 healthy subjects matched by age and gender as a control group. Medical history, physical examination and laboratory tests for confirming SLE diagnosis and assessment of disease activity were collected. The assessment of serum levels of studied cytokines were performed using the ELISA method.All studied patients after first cytokine evaluation were treated with a combination of antimalarial drugs, glucocorticosteroids and/or immunosuppressive drugs with follow-up after six months of treatment.ResultsIn the SLE group the mean serum levels of IL-34, IFN-α and IFN-λ1 were 175.9 ±125.9 pg/ml, 109.3 ±32.5 pg/ml and 227.9 ±144.8 pg/ml respectively. These cytokine levels were significantly higher in the SLE group than in healthy controls. 39% of SLE patients (n = 32) had SLAM > 6 and 26.8% (n = 22) had SLEDAI >6. There were 21 SLE patients (25.6%) with lupus nephritis.IL-34 and IFN-λ1 were positively correlated with anti-dsDNA antibodies but negatively correlated with C3 complement component (p ≤ 0.05). IL-34, INF-α and IFN-λ1 were significantly higher in lupus nephritis patients, and correlated with poorest response to treatment.IL-34 and IFN-λ1 were correlated with higher SLAM > 6 and SLEDAI > 6 results; there was no such correlation between IFN-α and disease activity.Accumulation of three or more clinical features during follow-up was significantly associated with high levels of studied cytokines. Triple high positivity was found in 17 patients (20.7%) and correlated with presence of anti-dsDNA antibodies, low levels of C3 component of complement and lupus nephritis.ConclusionsSLE patients with high serum levels of IL-34, IFN-α and IFN-λ1 more often had lupus nephritis and poor response to immunosuppressive treatment.The triple cytokine elevation was strongly associated with higher disease activity. These results may indicate the need to distinguish this group of patients with such aggressive phenotype and consider targeted multi-therapy.

Risk factors of damage in early diagnosed systemic lupus erythematosus: results of the Italian multicentre Early Lupus Project inception cohort.

To investigate risk factors for damage development in a prospective inception cohort of early diagnosed SLE patients. The Early Lupus Project recruited an inception cohort of patients within 12 months of SLE classification (1997 ACR criteria). At enrolment and every 6 months thereafter, the SLICC/ACR Damage Index was recorded. The contribution of baseline and time-varying covariates to the development of damage, defined as any SLICC/ACR Damage Index increase from 0 to ≥1, was assessed using univariate analysis. Forward-backward Cox regression models were fitted with covariates with P < 0.05 to identify factors independently associated with the risk of damage development. Overall, 230 patients with a mean (s.d.) age of 36.5 (14.4) years were eligible for this study; the mean number of visits per patient was 5.3 (2.7). There were 51 (22.2%) patients with SLICC/ACR Damage Index ≥1 after 12 months, 59 (25.6%) after 24 months and 67 (29.1%) after 36 months. Dyslipidaemia [P = 0.001; hazard ratio (HR) 2.9; 95% CI 1.5, 5.6], older age (P = 0.001; HR 3.0; 95% CI 1.6, 5.5), number of organs/systems involved (P = 0.002; HR 1.4; 95% CI 1.1, 1.8) and cardiorespiratory involvement (P = 0.041; HR 1.9; 95% CI 1.0, 3.7) were independently associated with an increased risk of developing damage. Risk profiles for damage development differed for glucocorticoid-related and -unrelated damage. HCQ use (P = 0.005; HR 0.4; 95% CI 0.2, 0.8) reduced the risk of glucocorticoid-unrelated damage. We identified risk factors of damage development, but little effect of glucocorticoids, in this early SLE cohort. Addressing modifiable risk factors from the time of SLE diagnosis might improve patient outcomes.

Correlation between Serum IL-6 Level and Th17/Treg Ratio with Systemic Lupus Erythematosus Disease Activity

Introduction: SLE pathophysiology shifted to a new paradigm which emphasizing the imbalance between Th17 and Treg. IL-6 is the main cytokine believed as the regulator of the balance between Th17 and Treg which play a big part in SLE pathophysiology and disease activity. The aim of this study was to determining the correlation between serum IL-6 level and Th17/Treg ratio with SLE disease activity on SLE inpatients of RSUD Dr. Soetomo Surabaya.Methods: This cross sectional study included newly diagnosed SLE patients based on American College of Rheumatology (ACR) 1997 revised criteria and confirmed by rheumatologist. All subjects underwent the same examination and assessment such as SLE disease activity was scored according to SLAM score, serum IL-6 level measured using ELISA, and Th17/Treg ratio where the expression Th17-Treg detected by flowcytometry method.Results: Thirty female subjects with active SLE had mean age 31,3 ± 10,46 years. The most frequent clinical manifestations were hematologic disorders and arthritis. Serum IL-6 level was significantly elevated in SLE patients compare to healthy subjects (200,61 pg/ml versus 45,9 pg/ml, p =0,028). Th17/Treg ratio were also significantly higher in SLE patients compared to healthy subjects (2,49 versus 1,20, p = 0,31). Th17/Treg ratio significantly correlated with SLE disease activity (r = 0,988; p&lt;0,05). There were no significant correlation between serum IL-6 level with Th17/Treg ratio (r = -0,095; p&gt;0,05) or even SLE disease activity (r = 0,066 ; p&gt;0,05). Conclusion: Serum IL-6 level had no significant correlation with Th17/Treg ratio or SLE disease activity. We found significant correlation between Th17/Treg ratio with SLE disease activity.

Initial disease severity, cardiovascular events and all-cause mortality among patients with systemic lupus erythematosus.

Objective SLE is associated with high risks of cardiovascular disease (CVD) and mortality, and has a wide spectrum of presentations. We investigated whether SLE severity at diagnosis was associated with CVD or mortality risk. Methods Within Medicaid (2000-10), we identified patients 18-65 years of age with incident SLE. Initial SLE severity was classified-mild, moderate, or severe-during the baseline year prior to the start of follow-up (incident index date) using a published algorithm based on SLE-related medications and diagnoses. Patients were followed from the index date to the first CVD event or death, disenrollment, loss to follow-up or end of follow-up period. Cox and Fine-Gray regression models, adjusted for demographics and comorbidities accounting for the competing risk of death (for CVD), estimated CVD and mortality risks by baseline SLE severity. Results Of 15 120 incident SLE patients, 48.7% had mild initial SLE severity, 33.9% moderate and 17.4% severe. Mean (s.d.) follow-up was 3.3 (2.4) years. After multivariable adjustment, CVD subdistribution hazard ratios (HRSD) were higher for initially severe [HRSD 1.64 (95% CI 1.32, 2.04)] and moderate [HRSD 1.19 (95% CI 1.00, 1.41)] SLE vs mild SLE. Mortality HRs were also higher for initially severe [HR 3.11 (95% CI 2.49, 3.89)] and moderate [HR 1.61 (95% CI 1.29, 2.01)] SLE vs mild SLE. Conclusion SLE patients with high initial severity had elevated mortality and CVD events risks compared with those who presented with milder disease. This has implications for clinical care and risk stratification of newly diagnosed SLE patients.

Initial disease severity, cardiovascular events and all-cause mortality among patients with systemic lupus erythematosus.

SLE is associated with high risks of cardiovascular disease (CVD) and mortality, and has a wide spectrum of presentations. We investigated whether SLE severity at diagnosis was associated with CVD or mortality risk. Within Medicaid (2000-10), we identified patients 18-65 years of age with incident SLE. Initial SLE severity was classified-mild, moderate, or severe-during the baseline year prior to the start of follow-up (incident index date) using a published algorithm based on SLE-related medications and diagnoses. Patients were followed from the index date to the first CVD event or death, disenrollment, loss to follow-up or end of follow-up period. Cox and Fine-Gray regression models, adjusted for demographics and comorbidities accounting for the competing risk of death (for CVD), estimated CVD and mortality risks by baseline SLE severity. Of 15 120 incident SLE patients, 48.7% had mild initial SLE severity, 33.9% moderate and 17.4% severe. Mean (s.d.) follow-up was 3.3 (2.4) years. After multivariable adjustment, CVD subdistribution hazard ratios (HRSD) were higher for initially severe [HRSD 1.64 (95% CI 1.32, 2.04)] and moderate [HRSD 1.19 (95% CI 1.00, 1.41)] SLE vs mild SLE. Mortality HRs were also higher for initially severe [HR 3.11 (95% CI 2.49, 3.89)] and moderate [HR 1.61 (95% CI 1.29, 2.01)] SLE vs mild SLE. SLE patients with high initial severity had elevated mortality and CVD events risks compared with those who presented with milder disease. This has implications for clinical care and risk stratification of newly diagnosed SLE patients.

Lactobacillus rhamnosus and Lactobacillus delbrueckii ameliorate the expression of miR-155 and miR-181a in SLE patients

BackgroundSystemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the production of autoantibodies and activated immune cells against self-antigens. Probiotics are known to possess anti-inflammatory and modulatory effects on the immune responses. In this study, we evaluated the effect of probiotics Lactobacillus rhamnosus and Lactobacillus delbrueckii on the expression levels of miR-155 and miR-181a in the PBMCs of SLE patients. MethodsA total of 20 newly diagnosed SLE patients and 20 healthy controls were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and treated with probiotics Lactobacillus rhamnosus (107 Bac/mL) and Lactobacillus delbrueckii (105 Bac/mL), and cultured in RPMI-1640 for 48 h. Afterwards, total RNA containing micro-RNAs were extracted. cDNA was synthesized for miRNAs and gene expression of miR-181a and miR-155 was analyzed using quantitative real-time PCR method. ResultsHigher expression levels of miR-181a and miR-155 were found in SLE patients compared with healthy controls. Treatment of PBMCs with L. rhamnosus, L. delbrueckii and combination of these probiotics downregulated the expression of miR-181a and miR-155 in treated cells compared with untreated cells. ConclusionsL. rhamnosus and L. delbrueckii modulate the expression of miR-181a and miR-155 in SLE patients and might be beneficial in the management of SLE patients.

Low Expression and Clinical Value of hsa_circ_0049224 and has_circ_0049220 in Systemic Lupus Erythematous Patients.

BackgroundThe aim of this study was to discuss the possible roles and clinical value of 2 circRNAs (hsa_circ_0049224 and has_circ_0049220) in SLE patients.Material/MethodsReverse-transcription real-time polymerase chain reaction (RT-PCR) was conducted to detect the expressions of hsa_circ_0049224, has_circ_0049220, and DNMT1 in peripheral blood mononuclear cells (PBMCs) from 18 diagnosed SLE patients and 10 healthy controls.ResultsWe found that the expressions of hsa_circ_0049224 and has_circ_0049220 in healthy control groups were both much higher than those in inactive and active SLE patients. The expression level of DNMT1 is positively correlated with the expressions of hsa_circ_0049224 and has_circ_0049220. Moreover, there was a negative correlation between the SLE Disease Activity Index (SLEDAI) and the expressions of hsa_circ_0049224 and has_circ_0049220. We also found that these 2 circRNAs are associated with some clinical characteristics of SLE.ConclusionsHsa_circ_0049224 and has_circ_0049220 are probable factors involved in the pathogenesis of SLE, and they have potential clinical value in SLE.

CE-21 The prevalence and determinants of ANTI-DFS70 antibodies in an international inception cohort of systemic lupus erythematosus (SLE) patients

Background When found in the absence of antibodies to extractable nuclear antigens (ENA) or anti-double-stranded DNA (dsDNA) (i.e., monospecific), autoantibodies to the nuclear autoantigen dense fine speckles 70 (DFS70) are purported to rule out SLE. The reported frequency of anti-DFS70 by chemiluminescence (CIA) in SLE is low compared to healthy individuals (0–5.7% vs. 1.3–23.2%), while the frequency of monospecific anti-DFS70 in SLE is even lower at 0–0.4%. There are no studies examining the frequency of anti-DFS70 in an early inception SLE cohort. This study determined the prevalence of anti-DFS70 in a multi-national, multi-ethnic early inception SLE cohort and examined demographic, clinical, and autoantibody associations. Materials and methods Patients fulfilling ACR Classification Criteria for SLE were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Demographic and clinical data were collected at enrollment. ANAs were detected by indirect immunofluorescence on HEp-2 cells (ImmunoConcepts, Sacramento) and ENAs and dsDNA by an addressable laser bead immunoassay (FIDIS Connective13, TheraDiag, Paris). Anti-DFS70 antibodies were measured by CIA (Inova Diagnostics, San Diego). The association between anti-DFS70 and baseline demographic, clinical, and autoantibody profiles was assessed using univariate and multivariate logistic regression. For the most informative model, only the remaining statistically significant predictors at the 95% CI: were included, after eliminating other potential predictors individually, starting with the least likely to be associated with the outcome. Results 1137 patients were included; 89.9% were female and 93.8% were ANA positive (Table 1). The frequency of anti-DFS70 was 7.1% [95% CI: 5.7–8.8%]. 13 of 1137 (1.1%) [95% CI: 0.6–1.9%] were positive for anti-DFS70 only (monospecific). In univariate analysis, patients with musculoskeletal activity (based on SLEDAI items) or anti-β−2 glycoprotein-1 (anti-β2GP1) were more likely to have anti-DFS70, whereas those with anti-dsDNA, anti-SSA/Ro60, anti-SSB/La, or anti-U1RNP were less likely to have anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odd Ratio (OR) 1.25 [95% CI: 1.10, 1.41]) or anti-β2GP1 (OR 2.15, 95% CI: 1.21, 3.84) were more likely to have anti-DFS70, while those with anti-dsDNA (OR 0.53, 95% CI: 0.31, 0.92) or anti-SSB/La (OR 0.25, 95% CI:0.08, 0.82) were less likely to have anti-DFS70. Conclusions The prevalence of anti-DFS70 in newly diagnosed SLE patients was at the high end of the range previously ?published for SLE (7.1% vs. 0–5.7%) and was associated with musculoskeletal activity and anti-β2GP1. However, ‘monospecific’ anti-DFS70 was rare (1.1%) and is potentially useful to discriminate between ANA positive healthy individuals and SLE.

Pseudotumor Cerebri as the First Manifestation of Juvenile Systemic Lupus Erythematosus

IntroductionHeadache is a common neuropsychiatric manifestation of juvenile systemic lupus erythematous (JSLE). Pseudotumor cerebri (PTC) is an uncommon cause of headache, presenting especially in active JSLE. In this paper, we report a case of missed intractable headache that was eventually diagnosed as PTC and presented as the first manifestation of JSLE.Case PresentationA 9-year-old girl with a history of progressive headache for four months, fever, fatigue, myalgia, arthralgia, small-joint arthritis of the hands, and recent diplopia was referred to our clinic. The diagnosis of PTC in the background of JSLE was made based on her history, physical examination, positive laboratory findings, and increased intracranial pressure, with normal neuroimaging. Treatment with high-dose prednisolone led to dramatic resolution of the headache.ConclusionsIt seems that a complete neurologic examination in newly diagnosed SLE patients is mandatory, especially in the presence of any neuropsychiatric manifestations, such as headache.

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus

ObjectiveNeutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have recently been investigated as two new inflammatory markers used in the assessment of systemic inflammation in many diseases. The purpose of the study was to investigate their relation with disease activity in newly diagnosed SLE patients. MethodsThe study population consisted of 116 SLE patients who did not receive any treatment and 136 healthy controls. We divided the patients into two groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K) system. Group 1 included patients with a score of 9 and lower (patients with mild disease activity), and Group 2 included patients with a score of >9 (patients with severe disease activity). Correlations between NLR, PLR and disease activity were analyzed. ResultsThe NLR and PLR of SLE patients were significantly higher compared to those of the controls (both P<0.001). There was a statistically significant difference in NLR and PLR between Group 1 and Group 2 (both P<0.05). SLEDAI scores positively correlated with NLR (r=0.312, P<0.001) and PLR (r=0.298, P<0.001). Furthermore, SLE patients with nephritis had higher NLR levels than those without nephritis (P=0.027). Based on the ROC curve, the best NLR cut-off value to predict SLE patients with severe disease activity was 2.26, with 75% sensitivity and 50% specificity, whereas the best PLR cut-off value was 203.85, with 42.3% sensitivity and 83.9% specificity. ConclusionNLR and PLR were two useful inflammatory markers for assessment of disease activity in patients with SLE.

Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study.

SLE is associated with increased risk of diabetes mellitus. Treatment for SLE requires high-dose glucocorticoids that may worsen glucose homoeostasis. HCQ can reduce diabetes risk in RA. This study aimed to investigate the association of HCQ use and diabetes mellitus risk in SLE patients. This nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. In the period 2001-10, 8628 newly diagnosed SLE patients were identified after excluding those with a previous diagnosis of RA, psoriasis or diabetes mellitus. Incidence of diabetes mellitus was identified as a new diagnostic code using a diabetes mellitus-specific medication. Two hundred and twenty-one newly diagnosed diabetes mellitus patients were identified among SLE patients (6795 had taken HCQ and 1833 had never taken HCQ), with an average follow-up period of 5.6 years. Compared with patients without HCQ treatment, the hazard ratio (HR) of diabetes mellitus in patients taking HCQ at a cumulative dose ≥129 g was reduced [HR 0.26 (95% CI 0.18, 0.37), P < 0.001]. Daily glucocorticoid ≥10 mg prednisolone-equivalent dose was associated with increased risk of developing diabetes mellitus [HR 2.47 (95% CI 1.44, 4.23), P = 0.001], which was minimized by concomitant HCQ use at a cumulative dose ≥129 g. In SLE patients, the use of HCQ is associated with reduced risk of incident diabetes mellitus in a dose-dependent manner. High-dose glucocorticoids increase the risk of diabetes, which can be decreased by concomitant HCQ use.

THU0163 Predictors of metabolic syndrome at enrolment into a multicentre international inception cohort of patients with SLE

BackgroundThe Metabolic Syndrome (MetS) is a clustering of metabolic abnormalities associated with an increased risk of developing diabetes and atherosclerosis, and may add to the increased cardiovascular risk seen in...

Early treatment with rituximab in newly diagnosed systemic lupus erythematosus patients: a steroid-sparing regimen

To assess the effectiveness of B-cell depletion therapy (BCDT) as a steroid-sparing treatment in newly diagnosed SLE patients. Eight female SLE patients were treated with BCDT using a rituximab/CYC-based regimen aiming to avoid the routine use of oral steroids. Post-treatment, patients were given AZA. The BILAG disease activity index was used for clinical assessment. Serum anti-dsDNA, complement (C3), ESR, circulating B lymphocytes (CD19(+)) and protein : creatinine ratio were tested at 0, 1, 3, 6 and 12 months post-treatment. Disease activity and steroid requirement over the first 6 months of treatment were compared with three SLE patients treated conventionally, each carefully matched for ethnicity, sex, age at disease onset and disease duration at diagnosis. All patients achieved B-cell depletion (CD19 count <0.005 × 10(9)/l). The mean decrease in global BILAG at 6 months for the BCDT patients was -12.0 vs 13.22 for the controls. Post-BCDT, no patient developed any significant deterioration, mean ESR fell from 70.12 to 17.14 mm/h at 6 months, mean serum anti-dsDNA antibody levels fell by >70% at 1 month and serum C3 level normalized in two patients by 6 months. There were no adverse events. The mean cumulative prednisolone dose at 6 months for the BCDT patients was 1287.3 mg (range 250-4501.8 mg) vs 2834.6 mg (range 0-6802.5 mg) for the controls. Early treatment of SLE patients with BCDT is safe and effective and enables a reduction in the overall steroid burden.

Selected angiogenic cytokines in systemic lupus erythematosus patients

The objective of this study was to determine the serum concentration of angiogenic factors (vascular endothelial growth factor, VEGF; transforming growth factor beta, TGF-β1; hepatic growth factor, HGF; basic fibroblast growth factor, bFGF; tumor necrosis factor alpha, TNF-α; soluble vascular endothelial growth factor receptor 1, sVEGF-R1; soluble vascular endothelial growth factor receptor 2, sVEGF-R2), the relationships among them and to assess the relation of their levels with the applied therapy in 48 females with systemic lupus erythematosus (SLE; 37 long-term treated +11 newly diagnosed). The control group consisted of 24 healthy women. A statistically significant increase of sVEGF-R2 and significant decrease of sVEGF-R1 were observed in the subgroup of newly diagnosed SLE patients as compared to the control subjects. No significant differences were found between serum angiogenic factors in the long-term treated subgroup and the control, the long-term treated subgroup and the newly diagnosed SLE patients after a 3-month treatment, and the subgroup of newly diagnosed SLE patients before therapy and after a 3-month treatment. The significant decrease in the serum of sVEGF-R2 was revealed in the subgroup treated for a long-time as compared to the subgroup of newly diagnosed untreated SLE patients. The analysis of relationships between serum concentration of sVEGF-R1 and other cytokines levels revealed positive correlation with concentration of VEGF and TNF-α in the total group of patients. In the newly diagnosed untreated subgroup, a strong positive correlation between concentration of sVEGF-R1 and bFGF was observed. Furthermore, a moderate positive correlation between concentration of sVEGF-R1 and the level of VEGF was revealed in the long-term treated patients. The association between sVEGF-R2 and HGF was also noted in this subgroup. The obtained data suggest the necessity of further investigations to determine the importance of angiogenic factors in pathogenesis and therapy of SLE.