Circulating IL-23 Levels and Correlation with SLE Disease Activity: A Meta-Analysis

Systemic Lupus Erythematosus (SLE) is characterized by exacerbation and remission, which needs close monitoring ofthe disease activity. Systemic lupus erythematosus disease activity can be determined by the SLE Disease Activity Index(SLEDAI) score. Evaluation of the disease activity is essential to be a guidance for treatment. Interleukin-34 (IL-34) is relatedto the pathogenesis of SLE. Serum IL-34 can be a candidate marker to evaluate SLE disease activity, and it is correlated withthe SLEDAI score. This study aimed to determine the correlation between IL-34 level and disease activity in SLE patientsbased on the SLEDAI (Mex-SLEDAI) score. An observational analytical study with a cross-sectional design was carried out insix months (June-November 2019) in 27 SLE patients in the Department of Internal Medicine, Faculty of Medicine, SumateraUtara University/Adam Malik General Hospital, Medan. Systemic lupus erythematosus disease activity was measured basedon the Mex-SLEDAI score. Serum and urine were collected to obtain the Mex-SLEDAI score and IL-34 level. IL-34 level wasmeasured in all subjects by using Enzyme-Linked Immunosorbent Assay (ELISA). Spearman correlation test was used todetermine the correlation between IL-34 level and disease activity in SLE patients based on the SLEDAI (Mex-SLEDAI) score.There was a significant correlation between IL-34 level and disease activity in SLE patients based on SLEDAI (Mex-SLEDAI)score (r=0.965, p < 0.001). Further studies were needed with a sample of SLE patients in a balanced proportion based ontheir disease activity to obtain representative IL-34 levels in SLE patients based on their disease activity.

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

Objectives The carotid intima-media thickness (CIMT) and carotid arterial stiffness index (CASI) act as the surrogate markers of atherosclerosis. We aim to assess CIMT and CASI in pediatric systemic lupus erythematosus (SLE). Methods Patients ≤ 20 years old fulfilling diagnostic criteria for SLE were enrolled. Patients with active smoking, coronary heart disease, cerebrovascular disease, arterial thrombosis, family history of hypercholesterolemia, chronic liver disease, or other chronic severe diseases were excluded. The patients were categorized into four groups: active SLE, age- and sex-matched control (control A), inactive SLE, and age- and sex-matched control (control I), according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). All subjects underwent ultrasound of carotid arteries to evaluate CIMT and CASI. Results One hundred and two SLE patients (26 active and 76 inactive) and one hundred and three healthy controls (26 control A and 77 control I) were enrolled. The median CIMT in all groups were not significantly different (0.43, 0.41-0.44; 0.43, 0.41-0.44; 0.42, 0.41-0.43; and 0.42, 0.41-0.43 mm, respectively).The CASI in active SLE (13.5, 11.4-17.3) was significantly higher than in control A (8.2, 7.2-9.2) ( p < 0.0001), whereas CASI in inactive SLE (12.7, 10.9-15.7) was significantly higher than in control I (8.9, 7.6-9.8). However, the CASI in active and inactive SLE was not significantly different. Conclusions The higher CASI in active and inactive pediatric SLE, implying functional change of carotid arteries, may be early evidence of increased atherosclerosis in pediatric SLE. This functional dysfunction has been found both in inactive and active SLE.

To evaluate the performance of 4 serum protein markers for detecting concurrent clinical activity in patients with systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥4 American College of Rheumatology classification criteria for SLE and healthy controls were recruited for serologic testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, insulin-like growth factor binding protein 2 (IGFBP-2), and tumor necrosis factor receptor type II (TNFRII). SLE disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician's global assessment (PGA). Levels of these markers were correlated with SLEDAI scores, and their sensitivity and specificity for clinical SLE activity were determined. A total of 94 SLE patients (98% women, mean ± SD age 28.7 ± 9.4 years, mean ± SD disease duration 5.4 ± 5.0 years) and 49 healthy controls were studied. Fifty-two patients had clinically active SLE (defined as SLEDAI score ≥6 or having a flare). The serum concentrations of Axl, ferritin, IGFBP-2, and TNFRII were significantly higher in patients with active SLE than in those with inactive SLE or in controls. The levels of these markers correlated strongly and significantly with anti-double stranded DNA (anti-dsDNA), C3, and clinical SLEDAI and PGA scores. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA or depressed C3. Levels of Axl, TNFRII, and IGFBP-2, but not ferritin, could differentiate active renal from active nonrenal or inactive SLE. The specificity of Axl and IGFBP-2 for concurrent active lupus nephritis was higher than anti-dsDNA or C3. Serum proteomic markers are potentially useful for diagnosing SLE and monitoring disease activity. The performance of Axl and IGFBP-2 in lupus nephritis should be further explored in a longitudinal cohort of SLE patients.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of multiple autoantibodies, resulting in tissue and organ damage. Recent studies have revealed that interleukin-23 (IL-23) and interleukin-27 (IL-27) may be therapeutically relevant in selected SLE manifestations. This study aimed to identify associations between serum IL-27 and IL-23 levels and disease activity in Polish patients with different manifestations of SLE: neuropsychiatric lupus (NPSLE), and lupus nephritis (LN). Associations between interleukin levels and oligo-specific antibodies against double-stranded DNA (dsDNA), dose of glucocorticoids, and type of treatment were also analyzed. An enzyme-linked immunosorbent assay was used to assess anti-dsDNA antibodies and analyze the serum concentration of IL-27 and IL-23 from 72 patients aged 19–74 years with confirmed active SLE. Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2-K). No significant correlations between interleukin levels and SLEDAI score, anti-dsDNA, corticosteroid dose, or type of treatment were noted. Patients with NPSLE and LN presented the highest median scores of SLEDAI.

Objective To investigate the correlation between neutrophil-lymphocyte ratio (NLR) and disease activity of systemic lupus erythematosus (SLE), and the changes of NLR in different organ involvement of SLE patients. Methods A total of 155 SLE patients and 135 healthy controls from the Rheumatology Department of Xiangya Hospital were enrolled in this study from 2010 to 2018. Patients with SLE were divided into lupus nephritis group (LN group) and non-lupus nephritis group (non-LN group), serositis group and non-serositis group, according to whether they had kidney involvement or serositis. According to the SLE disease activity index 2000(SLEDAI-2000), the patients were divided into mild to moderate disease activity group (SLEDAI score<15) and severe disease activity group (SLEDAI score≥15). The NLR values of the above groups were compared. Spearman's correlation analysis was used to analyze the correlation between NLR and SLE patients' laboratory indexes. Multiple linear regression model was used to analyze the relationship between NLR and SLE disease activity. Receiver operating characteristic curve (ROC) was used to evaluate the value of NLR in SLE diagnosis and activity assessment. Results (1)The NLR value of SLE patients was significantly higher than that of healthy control group, and the difference was statistically significant (P<0.01). (2)The NLR value of SLE patients in the LN group was higher than that in the non-LN group, and the NLR value of SLE patients with serositis was higher than that in the group without serositis, with statistically significant differences (both P<0.05). (3)The NLR value of SLE patients in the severe disease activity group was higher than that in the mild and moderate disease activity group, and the difference was statistically significant (P<0.01). (4)NLR of SLE patients was positively correlated with CRP (rs=0.188, P=0.019), SLEDAI score (rs=0.264, P=0.001), and negatively correlated with total serum protein (rs=-0.250, P=0.002) and serum albumin (rs=-0.329, P<0.001), respectively. (5) Multiple linear regression showed that NLR was independently associated with SLE disease activity(B=0.351, 95%CI 0.012-0.690, t=2.047, P=0.042). (6) According to ROC curve, the optimal cut-off value of NLR for SLE diagnosis was 2.17 (sensitivity 60.0%, specificity 83.1%, AUC=0.744), and the best cut-off value for predicting the activity of severe disease activity in SLE patients was 3.28 (sensitivity 58.5%, specificity 78.1%, AUC=0.700). Conclusion NLR is closely related to renal involvement, serositis and disease activity in SLE patients, which indicates that NLR, as a new inflammatory indicator, is of great significance for the assessment of SLE disease activity and organ involvement. Key words: Lupus erythematosus, systemic; Lupus nephritis; Serositis; Neutrophil-lymphocyte ratio; Disease activity

Introduction:Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune disease where an interplay between acute phase proteins and cytokines are involved in disease activation.Aim and Objectives:This case control study was performed to investigate interrelationship between high sensitivity C-reactive proteins (hs-CRP), Interleukin-6 (IL-6) levels and disease activity among SLE patients.Materials and Methods:One hundred forty one clinically diagnosed SLE cases were included and disease activity was noted by SLE Disease Activity Index (SLEDAI). Serum IL-6 levels were measure by cytokine multiplex assay. Serum hs-CRP, C3 and C4 levels were measure by nephelometer. The Pearson correlation test was used for correlation between hs-CRP, Il-6 and SLEDAI.Results:Based on SLEDAI, 126 patients (89.4 %) had active disease and 15 patients (10.6%) had inactive disease. Mean hs-CRP levels in SLE patients were significantly higher (12.1+ 11.5 mg/L) than controls (2.41+ 1.37 mg/L) (P < 0.0001). Hs-CRP levels among active SLE were significantly higher (13.5+ 11.4 mg/L) as compared with inactive SLE (4.4 + 2.9 mg/L) (P=0.0002). Similarly, IL-6 levels in SLE patients were significantly higher among active SLE (26.9 + 15.5 pg/ml) as compared with inactive SLE (13.9+ 10.2 pg/ml) (P=0.0001). An inverse correlation between Il-6 and hemoglobin levels between active and inactive SLE was noted (r=-0.46, P <0.0001).Conclusion:This study suggests a good correlation between hs-CRP, IL-6 and SLE disease activity indicating their direct involvement in inflammatory conditions associated with disease.

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

Serum leucine-rich α2-glycoprotein is elevated in patients with systemic lupus erythematosus and correlates with disease activity

SAT0234 SERUM AXL, FERRITIN, IGFBP4 AND STNFR2 AS BIOMARKERS OF PEDIATRIC SLE

We measured the interleukin-34 (IL-34) level in sera from patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) using an enzyme-linked immunosorbent assay (ELISA). Blood tests, including assays to determine C-reactive protein (CRP), complement (C) 3, C4, immunoglobulin (Ig) A, IgG, IgM, anti-double-stranded DNA antibody (Anti-dsDNA Ab) and hemoglobin (Hb) levels and white blood cell (WBC) and platelet (PLT) counts, were performed using standard methods. Lupus nephritis (LN) was diagnosed according to the American College of Rheumatology (ACR) renal criteria. The SLE disease activity was scored using the SLE Disease Activity Index (SLEDAI). Among the 110 SLE cases, IL-34 could be detected in 79 cases (71.8%). IL-34 was barely detected in the control group. The serum level of IL-34 was significantly higher in the SLE group. No change was observed in the serum IL-34 concentration in the SLE patients regardless of LN status. Correlations were observed between the serum IL-34 level and the disease activity parameters. The SLE patients with detectable IL-34 levels had higher SLEDAI and IgG concentrations and lower C3 and Hb levels than patients with undetectable IL-34 levels. Therefore, IL-34 could be a potential disease activity marker for SLE.

BACKGROUND AND AIMS Galectin-9, interferon-inducible protein-10 (IP-10) and sialoadhesin (SIGLEC-1) are considered as potential biomarkers reflecting disease activity in patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum and urine galectin-9, IP-10 and SIGLEC-1 with disease activity in patients with SLE. Also, we compared the results with ANCA-associated vasculitis (AAV) to test the specificity of the biomarkers. METHOD A total of 63 patients with active SLE (31 renal and 32 extrarenal) were included in the study. A total of 30 patients with inactive SLE (15 renal and 15 extrarenal), 17 with renal active AAV and 32 healthy volunteers were selected as control groups. Serum (s) and urine (u) levels of galectin-9, IP-10 and SIGLEC-1 were tested using ELISA. Urine levels of biomarkers were normalized by urine creatinine. RESULTS Of 142 participants, 109 (76.7%) were female and median age was 36 (28.75–48) years. Groups were comparable with regard to sex and age distribution except for AAV. In AAV group, seven patients (41.1%) were female and median age was 60 (48–65.5) years. Proliferative lupus nephritis (LN) (class III/III + V and IV/IV + V) were found in 22 patients with active renal SLE (70.9%), while 6 patients (19.3%) had pure class V and 3 (9.7%) had class II LN. Levels of sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 were significantly higher in the active SLE group compared to the inactive SLE group (sIP-10; P = 0.046, uIP-10; P &amp;lt; 0.001, sGalectin-9; P = 0.031 and uSIGLEC-1; P = 0.006); however, no differences were detected in the comparison of uGalectin-9 and sSIGLEC-1 between these two groups (uGalectin-9; P = 0.180 and sSIGLEC-1; P = 0.699). sIP-10 (P &amp;lt; 0.001), uIP-10 (P = 0.029) and uGalectin-9 (P &amp;lt; 0.001) were significantly higher in patients with active SLE compared to AAV (Table 1). Serum and urine galectin-9, IP-10 and SIGLEC-1 did not differ between patients with active renal and extrarenal SLE. Levels of sIP-10, uIP-10 and uSIGLEC-1 were correlated with SLE Disease Activity Index (SLEDAI). ROC analyses confirmed that sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 discriminated disease activity in SLE (Figure 1). Serum and urine levels of all biomarkers were retested in 41 of 63 patients (65%) with active SLE after a median treatment of 8 (5–22.5) months. At the time of the second tests, there was a significant decrease in disease activity as measured by SLEDAI [2 (0–4)] compared to the time of the first tests [10 (6–15.5)]. Comparison of sGalectin-9 levels between the sample at the time of active disease and remission showed a very significant decline (P &amp;lt; 0.001). uGalectin-9, sIP-10 and uSIGLEC-1 also decreased after treatment; however, the difference was not statistically significant. CONCLUSION sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 are associated with disease activity in SLE. None is able to discriminate active renal from active extrarenal disease. sIP-10 and uIP-10 are specific for active SLE compared to renal active AAV. sGalectin-9 may be a valuable biomarker to monitor response after treatment for active disease. Funded by Scientific Research Projects Coordination Unit of Istanbul University. Project number: TSA-2019–34 218.

Background/aimIn this prospective study, we aimed to investigate the association of serum (s) and urine (u) IP-10, galectin-9, and SIGLEC-1 with disease activity in patients with systemic lupus erythematosus (SLE).Materials and methodsSixty-three patients with active SLE (31 renal, 32 extrarenal) were included. Thirty patients with inactive SLE (15 renal, 15 extrarenal), 17 with renal active AAV, and 32 healthy volunteers were selected as control groups. Serum and urine IP-10, galectin-9, and SIGLEC-1 were tested using ELISA.ResultsLevels of sIP-10 (p = 0.046), uIP-10 (p < 0.001), sGalectin-9 (p = 0.03), and uSIGLEC-1 (p = 0.006) were significantly higher in active SLE group compared to the inactive SLE; however, no differences were detected in the comparison of uGalectin-9 (p = 0.18) and sSIGLEC-1 (p = 0.69) between two groups. None of the biomarkers discriminated patients with active renal SLE from active extrarenal SLE. ROC analyses revealed an AUC of 0.63 (0.52–0.73) for sIP-10, 0.78 (0.68–0.86) for uIP-10, 0.64 (0.53–0.74) for sGalectin-9, and 0.68 (0.57–0.77) for uSIGLEC-1 in discriminating disease activity in SLE, which did not outperform C3 (0.75, 0.64–0.84) and C4 (0.72, 0.61–0.82). sIP-10 (p = 0.001), uIP-10 (p = 0.042), and uGalectin-9 (p = 0.009) were significantly increased in patients with active renal SLE compared to active renal AAV. sGalectin-9 (p < 0.001) and sIP-10 levels (p = 0.06) were decreased after 8 (5–22.5) months of treatment.ConclusionsIP-10, uIP-10, sGalectin-9, and uSIGLEC-1 reflect global disease activity in SLE but do not outperform C3 and C4. sIP-10 and uIP-10 may be specific for active SLE compared to active AAV. sIP-10 and sGalectin-9 might be valuable in monitoring response after treatment.

Background TWEAK, MCP-1 and NGAL, mediators in pathogenesis of systemic lupus erythematosus (SLE), are proinflammatory cytokines/chemokines that are thought as potential biomarkers reflecting disease activity. In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and non-renal SLE. Methods Thirty active patients with SLE (15 renal and 15 non-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 non-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. Results Sixty-one SLE patients, 51 (83.6%) of whom were female, with a median disease duration of 83 (23.5–135) months and a median age of 35 (27–47.5) were included in the study. Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared with the inactive SLE (n=31) group (sTWEAK: p=0.005; uTWEAK: p=0.026; sNGAL: p Conclusions sTWEAK, uTWEAK, sNGAL and uNGAL are significant biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV. sTWEAK may be of use for discriminating active nephritis from non-renal active disease in SLE. Further studies are awaited to confirm these Results Funding Source(s): This study was funded by Istanbul University with the project number TTU-2017–24 738

SAT0184 ASSOCIATION OF SERUM AND URINE LEVELS OF TWEAK, MCP-1 AND NGAL WITH DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS