Activity In SLE Research Articles

Mean platelet volume is a marker of inflammation but not a marker of disease activity in children with juvenile SLE

Aim of the workTo study the mean platelet volume (MPV) in children with juvenile-onset SLE (Jo-SLE), and whether MPV can be used as a biologic marker for disease activity or flare. Patients and methodsTwenty-nine patients from the rheumatology outpatient clinic, Pediatric Cairo University Hospitals and age 36 and gender matched healthy controls were included in the study. The MPV was determined within 4h of blood sampling in all study populations. Recent routine laboratory investigations for Jo-SLE patients were obtained. Disease activity was estimated using SLE disease activity index (SLEDAI). Results29 Jo-SLE patients had a mean age of 12.8±2.9years and disease duration of 3.5±3year. The most frequent clinical manifestations were photosensitivity, malar rash, followed by arthritis and serositis. The MPV in Jo-SLE patients was 8.2±2.1femtoliters (fL) compared with 5.6±0.9fL in healthy controls (p<0.001). There was no significant difference between MPV in 18 active patients (8.3±2.1fL) compared to 11 patients with inactive disease (8.1±2.5fL). Furthermore, there were no significant correlations between the MPV and SLEDAI score (r=−0.19, p=0.33), or between MPV and other disease parameters routinely used to estimate disease activity or flare. ConclusionResults of the present study confirm the association between MPV and inflammation, but do not support the use of MPV as an indicator for monitoring disease activity or flare in juvenile SLE. Further longitudinal studies with larger numbers of patients are warranted to unveil the possibility of using MPV as a biologic marker of disease activity.

Interleukin 1 receptor antagonist (IL1Ra) VNTR polymorphism influences circulatory IL1Ra levels and development of SLE in South Indian Tamils

BackgroundSystemic lupus erythematosus (SLE) is a systemic autoimmune disease with complex aetiology. Genetic polymorphisms disrupting the functions of genes encoding anti-inflammatory cytokines such as IL1Ra may influence the disease activity and outcome in SLE. In this study, the IL1Ra VNTR polymorphism was tested for its influence on disease susceptibility, clinical and serological phenotypes of SLE in South Indian Tamils. Materials and methodsThree hundred SLE patients and 460 age, sex and ethnicity matched controls were genotyped for IL1Ra VNTR polymorphism by PCR. Serum IL1Ra was quantified by ELISA. ResultsGenotyping revealed that the four and two repeats were the most frequent polymorphic alleles in our subjects. The two repeat allele (A2) was more frequent in SLE (18%) than in controls (9%) and it conferred a significant risk to develop SLE [p=0.0001, OR 2.36, 95% CI, 1.7–3.2]. However, incidence of heterozygous genotype (A1A2) was high among SLE patients (25%) and presence of which was observed to influence the development of SLE [p=0.0001, OR 5.8, 95% CI, 3.2–9.5]. Quantification of serum IL1Ra revealed that the four repeat allele was associated with the normal production of the cytokine, whereas the other variants were associated with the reduced expression of the IL1Ra. ConclusionIL1Ra VNTR polymorphism analysis in South Indian Tamil SLE patients revealed that the genotype A1A2 was associated with lupus susceptibility. The VNTR polymorphism encoding the allele with two repeats was associated with reduced circulatory concentration of IL1Ra in SLE patients, likely predisposing them to develop clinically severe form of the disease.

From BILAG to BILAG-based combined lupus assessment-30 years on.

Disease activity in SLE can be difficult to measure and there is no biomarker that uniformly reflects disease activity. There are various disease activity scores, but there is no gold standard assessment tool. This is a review of the development of the BILAG index from the classic BILAG disease activity index to the BILAG-2004 disease activity index and composite response criteria. The original classic BILAG index was revised and distinguished nine organs/systems. Features that indicated damage, such as avascular necrosis, were excluded. There was improvement in the glossary, scoring system and software. The BILAG-2004 index has been shown to be reliable, valid and sensitive to change. The BILAG-2004 index has been modified for pregnancy and has also been used in paediatrics. The SLE Responder Index (SRI) and the BILAG-based combined lupus assessment (BICLA) are composite responder indices incorporating the BILAG index. Since the initial development of the BILAG index in 1984, major improvements have been made in the measurement of disease activity in lupus. However, the BILAG-2004 index is the only transitional index that grades clinical features as being new, the same, worse or improving and incorporates severity in the scoring.

Connective tissue diseases: Large intergenic noncoding RNA linked to disease activity and organ damage in SLE.

Connective tissue diseases: Large intergenic noncoding RNA linked to disease activity and organ damage in SLE

ESR, uric acid and its correlation with disease activity in SLE – Is it a myth or reality!!!!

ESR, uric acid and its correlation with disease activity in SLE – Is it a myth or reality!!!!

69: IL-6 and CH50 for monitoring of disease activity in systemic lupus erythematosus

Aims Low levels of complement 3 (C3) and 4 (C4) are known to be associated with disease activity in SLE. Recently automated IL-6 test is introduced to clinical laboratories. We aimed to determine the IL-6 and complements (C3, C4, and CH50) to find out the usefulness as monitoring markers for disease activity in SLE. Methods Eighty-seven SLE patients were studied. The patients were categorized as three groups according to the levels of C3 and C4; a group with normal C3 and C4 (37 patients), decreased C3 and normal C4 (38 patients) and decreased both C3 and C4 (12 patients). Plasma levels of IL-6 and CH50 were measured in those patients with additional healthy subjects. Kruskal–Wallis test was performed among the groups. Results Healthy subjects and the three groups (normal C3 and C4, decreased only C3, and decreased both complements) showed the median level of IL-6 less than 1.50, 2.74, 2.12, and 3.04 pg/mL; CH50 were 28.15, 18.65, 18.70, and 6.90 U/mL, respectively. Levels of IL-6 and CH50 showed no statistically significant differences among the patient subgroups. However, the data of all the SLE groups showed higher IL-6 ( p p = 0.05). Conclusions In SLE patients, plasma IL-6 levels were significantly increased, and that of CH50 were declined in patients with both C3 and C4 decreased. IL-6 may be a useful marker for differentiation of SLE patients from healthy subjects. Further prospective studies on the usefulness of IL-6 are helpful for SLE disease activity.

Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p < 0.001). The psoriasis group also had a significantly high mean melting temperature (78.62 ± 0.20) when compared with the inactive SLE group (78.49 ± 0.29, p < 0.05) and control group (78.44 ± 0.25, p < 0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28 ± 0.21 vs 78.44 ± 0.25, p < 0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.

SAT0012 Serum Sil7r Concentrations Reflect Disease Activity in the Lupus Kidney

BackgroundEvaluation of disease activity in SLE nephritis is a challenge, and repeated renal biopsies are usually needed in order to confirm a suspicion of flare. In a previous cross-sectional study,...

AB0515 Salivary Alpha-Amylase and Antichromatin Antibody Are Elevated and Associated with Disease Activity in Sle

BackgroundPsychological stress has been known as one of triggering factors in systemic lupus erythematosus (SLE). Saliva can be obtained easily without any invasive or painful procedure. Previously it has not...

OP0214 Identification of Gene Transcripts and Proteins That Independently PREDICT SLE Disease Activity over the Next Year

BackgroundIt is important to identify biomarkers of SLE disease activity for patient care, research, and drug development. Many gene transcripts and proteins in blood or urine have been observed to...

Disease activity in lupus correlates with expression of the transcription factor ARID3a (BA2P.119)

Abstract Systemic lupus erythematosus (SLE) is a complex autoimmune disease with striking clinical, immunologic and genetic heterogeneity making development of targeted treatment strategies challenging. Previously, we showed transgenic mice with constitutive expression of the DNA-binding protein ARID3a/Bright in all B lymphocytes spontaneously produced autoantibodies. Therefore, we asked if ARID3a expression differed in SLE versus healthy control B lymphocytes. Of 114 SLE patients, 43% had expanded numbers of ARID3a+ peripheral blood B cells. A longitudinal study revealed that numbers of ARID3a+ B cells fluctuated with time, but were highly associated with increased disease activity. ARID3a expression was not limited to B cell subsets that normally express it, but was also apparent in large numbers of naïve B cells in many SLE patients. Therefore, we hypothesize ARID3a+ naïve B cells are precursors of autoantibody producing B cells. Antibody repertoire analyses of ARID3a+ and ARID3a- naïve B cells are in progress. Together, these findings implicate ARID3a as a potential biomarker for disease activity in SLE.

Supervised physical exercise improves endothelial function in patients with systemic lupus erythematosus

The objective of this study was to evaluate the effect of supervised physical exercise on endothelial function, ergospirometric test variables and disease activity in SLE patients. We conducted a prospective study in which women with SLE who were available to perform physical exercise were allocated to the exercise group (EG) to practise supervised physical exercise for 1 h three times per week for 16 weeks. Those who were not available for this activity were allocated to the control group (CG). Intervention consisted of walking at a heart rate corresponding to the ventilatory 1 threshold obtained from ergospirometry and monitored by a frequency meter. At baseline (T0) and after 16 weeks (T16), patients were assessed for endothelial function by brachial artery (flow-mediated dilation), ergospirometry and disease activity (SLEDAI). Statistical analysis was performed through normality tests, Student's t-test and non-parametric tests for data with non-normal distribution. P < 0.05 was considered significant. Eighteen patients were allocated in the EG and 20 in the CG. After 16 weeks there was an increase in FMD in the EG [6.3 (6.7)% vs 14.1 (9.1)%, P = 0.006] without a change in the CG [8.4 (8.2)% vs 9.4 (5.7)%, P = 0.598]. Regarding the ergospirometric test, we found improvement in exercise tolerance [12.3 (2.4) vs 13.4 (2.6) min, P = 0.027], maximum speed [7.7 (1.0) vs 8.3 (1.2) km/h, P = 0.027] and threshold speed [5.6 (0.7) vs 6.1 (0.9) km/h, P = 0.005] in the EG without a difference in the CG. There was no difference in the SLEDAI score in both groups. Physical exercise is a useful strategy to improve endothelial function and aerobic capacity without worsening disease activity in SLE patients. TRIAL REGISTRATION; ClinicalTrials.gov (http://www.clinicaltrials.gov), NCT01712529.

FRI0167 Anti-TNF do not modify the interferon signature in patients with rheumatoid arthritis and lupus (“rhupus”)

BackgroundWe recently reported the clinical efficacy and safety of anti-TNF-alpha in a cohort of 15 rhupus patients with rheumatoid arthris and systemic lupus (“rhupus”). TNF-alpha and type I interferon (IFN)...

THU0195 IFNα and its response proteins IP-10 and SIGLEC-1 as biomarkers of disease activity in systemic lupus erythematosus

BackgroundOver the decades, IFNα has been identified as a key cytokine predisposing and driving systemic lupus erythematosus pathology and is thus a frequently studied target molecule. It is assumed that...

THU0177 ESR as a predictor of SLE disease activity and damage

BackgroundThe erythrocyte sedimentation rate (ESR) is an inexpensive laboratory test for assessing the inflammatory response but is influenced by a wide range of factors, many of them unrelated to inflammation.ObjectivesTo...

Th1/Th2 cytokine profile in childhood-onset systemic lupus erythematosus

ObjectiveTo determine the serum levels of Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-5, IL-6 and IL-10) cytokines in childhood-onset SLE, first-degree relatives and healthy controls. To elucidate their association with disease activity, laboratory and treatment features. MethodsWe included 60 consecutive childhood-onset SLE patients [median age 18years (range 10–37)], 64 first-degree relatives [median 40 (range 28–52)] and 57 healthy [median age 19years (range 6–30years)] controls. Controls were age and sex-matched to SLE patients. SLE patients were assessed for clinical and laboratory SLE manifestations, disease activity (SLEDAI), damage (SDI) and current drug exposures. Mood and anxiety disorders were determined through Becks Depression (BDI) and Anxiety Inventory (BAI). Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-5, IL-6 and IL-10) cytokines levels were measured by ELISA and compared by non-parametric tests. ResultsSerum TNF-α (p=0.004), IL-6 (p=0.007) and IL-10 (p=0.03) levels were increased in childhood-onset SLE patients when compared to first-degree relatives and healthy controls. TNF-α levels were significantly increased in patients with active disease (p=0.014) and correlated directly with SLEDAI scores (r=0.39; p=0.002). IL-12 (p=0.042) and TNF-α (p=0.009) levels were significantly increased in patients with nephritis and TNF-α in patients with depression (p=0.001). No association between cytokine levels and SDI scores or medication was observed. ConclusionTh1 cytokines may play a role in the pathogenesis of neuropsychiatric and renal manifestations in childhood-onset SLE. The correlation with SLEDAI suggests that TNF-α may be a useful biomarker for disease activity in childhood-onset SLE, however longitudinal studies are necessary to determine if increase of this cytokine may predict flares in childhood-onset SLE.

Expression of Toll-like receptors and their detection of nuclear self-antigen leading to immune activation in JSLE

Toll-like receptors (TLRs) essential in the functioning of the immune system have been implicated in the development of autoimmunity. TLR3, 7, 8 and 9 are capable of recognizing nucleic autoantigens typical of SLE. Their expression correlates positively with disease activity in adult-onset SLE. This study aimed to determine the role of TLRs in JSLE and whether apoptotic neutrophils are a source of nuclear autoantigen being detected through TLR3, 7, 8 and 9, leading to an inflammatory response. TLR3, 7, 8 and 9 mRNA and protein expression were measured in peripheral blood mononuclear cells (PBMCs) in JSLE patients compared with JIA and non-inflammatory controls. Activation of the TLRs by JSLE serum-induced apoptotic neutrophils was detected by measuring IFN-α mRNA and protein expression, and confirmed using myeloid differentiation factor 88 (MyD88) and TIR domain-containing adapter-inducing IFN-β (TRIF) inhibitors. JSLE patients have increased TLR3, 8 and 9 mRNA and protein expression compared with controls (P < 0.05). Incubation of PBMCs with apoptotic neutrophils demonstrated a dose-response relationship for IFN-α mRNA expression. Inhibition of TLR signalling by blocking MyD88 and TRIF signalling decreased IFN-α mRNA expression in PBMCs incubated with apoptotic neutrophils (P < 0.05). This study demonstrated significantly increased TLR expression in JSLE compared with controls. Our data indicate that apoptotic neutrophils trigger TLR activation through their presentation of autoantigens. The role of TLRs in this inflammatory response was demonstrated by a dose-response relationship to apoptotic neutrophil concentration and confirmed by a decrease in IFN-α production after inhibition of TLR signalling.

Active regulatory T-cells contribute to broadened T-cell repertoire diversity in ivIg-treated SLE patients

Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus. Relative oligoclonality of circulating T-cells in SLE has been reported. Also CD4+Foxp3+ regulatory T-cells (Tregs) have a characteristically reduced activity in SLE, reflected by CD25 surface density. Aiming to study the role of Tregs for ivIg therapy, we characterized Tregs and determined TCR spectratypes of four Vb families with reported oligoclonality, in 15 lupus patients (14 with SLE and one with discoid LE) treated with ivIg in cycles of 2-6 consecutive monthly infusions. Among these 15 patients, 11 responded with clinical improvement. Cell counts, cytometry and TCR spectratypes were obtained from peripheral blood at various time points before, during and after ivIg treatment. T-cell oligoclonality was assessed as Vb-familywise repertoire perturbation, calculated for each patient in respect to an individual reference profile averaged over all available time points. For 11/15 patients, average Vb1/Vb2/Vb11/Vb14 repertoires were less perturbed under ivIg treatment than outside ivIg therapy. The four exceptions with relatively increased average perturbation during ivIg therapy included three patients who failed to respond clinically to an ivIg therapy cycle. Patients' Treg CD25 surface density (cytometric MFI) was, other than Treg/CD4+ frequency, clearly reduced when compared to healthy controls, but not obviously influenced by ivIg. However, patients' average Treg CD25 MFI was found negatively correlated with both Vb11 and Vb14 perturbations measured under ivIg therapy, which indicates a role of active Tregs in the therapeutic effect of ivIg.

Antinucleosome antibodies as a potential biomarker for the evaluation of renal pathological activity in patients with proliferative lupus nephritis

The objective of this study is to evaluate the correlation between antinucleosome antibodies and renal pathological activity in patients with proliferative lupus nephritis (LN). We evaluated 36 patients with proliferative LN, 14 non-renal lupus patients and 10 healthy volunteers. Lupus activity was assessed using the British Isles Lupus Assessment Group 2004 (BILAG 2004) index, serum anti-double stranded DNA (anti-dsDNA) levels, serum complement levels and daily urinary protein levels. All 36 lupus nephritis patients received renal biopsy. Antinucleosome antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Our results showed that levels of serum antinucleosome antibodies were significantly higher in LN patients (median 90.35 units/ml, interquartile range [IQR] 37.38-135.23) than in non-renal SLE patients (median 5.45 units/ml, IQR 2.6-28.93, p <0.05) and in healthy volunteers (median 3.35 units/ml, IQR 2.95-5.23, p <0.001). Serum levels of antinucleosome antibodies were positively correlated with BILAG index (Spearman's r = 0.645, p <0.001) and serum anti-dsDNA antibody levels (r(s) = 0.644, p <0.01), while serum levels of antinucleosome antibodies were negatively correlated with serum levels of C3 (r(s) = -0.400, p <0.01) and C4 (r(s) = -0.300, p <0.05). Serum levels of antinucleosome antibodies were positively correlated with the histological activity index of LN (r(s) = 0.368, p <0.05). However, there was no significant correlation between serum levels of antinucleosome antibodies and the histological chronicity index. In conclusion, the serum level of antinucleosome antibodies is a potential biomarker for early recognition of renal involvement and evaluation of disease activity in SLE. Our preliminary results suggested that serum levels of antinucleosome antibodies might be a potential biomarker in evaluating pathological activity of LN.

Interaction between oxidative stress and chemokines: Possible pathogenic role in systemic lupus erythematosus and rheumatoid arthritis

Imbalance oxidative stress and chemokines are considered as a universal factors involved in the development of various clinical features seen in the patients with SLE and arthritis. To evaluate the interaction between oxidative stress and chemokines and their relationship with disease activity in SLE and RA patients, oxidative/anti-oxidant profiles and chemokines were assessed. Oxidant and anti-oxidant enzymes were measured in the plasma and the levels of chemokines; MCP-1/CCL2, RANTES/CCL5, MIP-1β/CCL-4 and IP-10/CXCL-10 were evaluated in the serum by an enzyme-linked immunosorbent assay (ELISA). A significant increase in the level of lipid peroxidation was found in SLE and RA patients and positively associated with disease activity. The activities of anti-oxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and anti-oxidant molecule GSH were significantly reduced in both diseases. Strong positive associations were found between MDA with RANTES/CCL5 and MIP-1β/CCL4 than MCP-1/CCL-2 in SLE patients while a sturdy connotation was seen with MIP-1β/CCL4 and MCP-1/CCL-2 in RA patients. The anti-oxidant molecule GSH shows a negative association with serum levels of MCP-1/CCL-2, RANTES/CCL5 and IP-10/CXCL-10 in SLE patients and with MCP-1/CCL-2 and RANTES/CCL5 in RA patients. A low level of GSH and high level of RANTES/CCL5 were associated with lupus nephritis patients. These results indicates that excessive production of ROS disturbs redox status and can modulate the expression of inflammatory chemokines leading to inflammatory processes, exacerbating inflammation and affecting tissue damage in autoimmune diseases, as exemplified by their strong association with disease activity.