Renal SLEDAI Research Articles

The value of renal color Doppler ultrasound as an objective tool in the diagnosis of renal affection in SLE patients

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease with diverse manifestations, which resembles a clinical challenge to be managed. Lupus nephritis is a life-threatening condition as about 10% of patients develop chronic kidney disease.Aim of the workTo assess the role of resistive index (RI) as a noninvasive parameter in detecting renal affection in SLE patients.ResultsA case–control study included 3 matched groups: 30 patients, 15 SLE with no renal affection, and 15 SLE lupus nephritis patients, who were selected, diagnosed according to ACR criteria 2019 for SLE, beside 15 age- and gender-matched healthy controls without any risk factors of chronic diseases. Written informed consent was obtained from all the three groups, and the study was approved by ethical committee. There was a statistically significant increase in both SLEDAI and renal SLEDAI scores, serum BUN, creatinine, urinary pus cells, RBCs, casts and proteins, 24-h urinary proteins, and protein/creatinine ratio beside a statistically significant increase in both right and left resistive indices in the group of lupus nephritis than the other group. There was highly statistically significant difference between SLE without nephritis and SLE with nephritis regarding renal echogenicity. There was statistically significant positive correlation between average RI and SLEDAI, rSLEDAI, serum creatinine, BUN, 24-h urinary proteins, protein/creatinine ratio, and renal echogenicity. Relation between renal echogenicity and demographic, laboratory, and clinical data was highly statistically significant with rSLEDAI, serum creatinine, BUN, 24-h urinary proteins, and P/C ratio. Our study highlighted that the best cutoff point of Rt average RI to detect SLE with nephritis group was found > 0.68 with sensitivity of 86.7% and specificity of 100.0%, while the best cutoff point of left average RI to detect SLE with nephritis group was found > 0.7 with sensitivity of 80.0% and specificity of 100.0%.ConclusionRenal RI is a noninvasive technique that can be used for detection renal disease activity in SLE patients, together with renal parenchymal echogenicity by grayscale US.

Soluble urine activated leukocyte cell adhesion molecule is a strong predictor of lupus nephritis.

To evaluate urinary activated leucocyte cell adhesion molecule (ALCAM) and CD6 as predictors of lupus nephritis (LN) progression or disease resolution across a 1-year study. Serum and urine samples from biopsy proven LN subjects (n = 122) were prospectively collected over the course of a year at 3- or 6-month intervals (weeks 0, 12, 26, and 52) across multiple study sites and assessed for soluble ALCAM and CD6 levels. Urine creatinine from the same urine sample was used to normalize the levels of urinary ALCAM and urinary CD6. Measured levels of serum and urine ALCAM and CD6 were then analyzed against disease metrics cross-sectionally and longitudinally. Cross-sectional analysis at baseline revealed that urinary ALCAM significantly correlated with urine protein creatinine ratio (UPCR), renal SLEDAI, and the Physician Global Assessment (PGA), and negatively correlated with serum C3 and C4. Receiver operating characteristic (ROC) curve analysis demonstrated that urinary ALCAM is a predictor of LN with an area under the curve (AUC) of 0.97, compared with urinary CD6 with an AUC of 0.71. Importantly, the change in urinary ALCAM over a 3-month period distinguished between non-responders and responders at week 52. Urinary ALCAM is reflective of changes in LN and may be predictive of response status.

The ratio of neutrophil to lymphocyte as a potential marker of clinicopathological activity for lupus nephritis.

The ratio of neutrophil to lymphocyte (NLR) is a novel inflammatory factor that is elevated in systemic lupus erythematosus (SLE). However, the relationship between NLR and renal pathological manifestations in patients with lupus nephritis (LN) has not been investigated. A retrospective study included 240 SLE patients, in which 186 patients with renal involvement and 124 LN patients underwent renal biopsy, 125 healthy volunteers and 125 chronic kidney disease (CKD) controls. Patients with SLE disease activity 2000 (SLEDAI-2K) > 9 and ≤ 9 were defined as severely active and mildly active, respectively. Clinical parameters and renal pathological data were collected from medical records. The correlations between NLR and clinicopathological features were analyzed. The NLR of SLE group was significantly higher than that of the sex-age matched control groups. Patients with nephritis had higher NLR levels than those without nephritis (P = 0.044). Increased NLR was observed in severely active group compared to mildly active group (P = 0.020). NLR was significantly positively related with SLEDAI score, Renal SLEDAI score, C-reactive protein (CRP), 24-h urine protein, renal activity index (AI), cellular crescents and tubular atrophy, and negatively correlated with serum albumin. NLR was significantly decreased after treatment. Based on the receiver operating characteristic (ROC) curve, the best NLR cut-off value to predict severe activity of SLE and cellular crescents in renal pathology was 2.19 and 3.16, respectively. NLR may be a non-invasive and potential inflammatory marker in evaluating clinical and renal pathological activity in LN patients.

#4844 BELIMUMAB AND MULTITARGET THERAPY AS INDUCTION THERAPY OF SEVERE ACTIVE LUPUS NEPHRITIS: CASE SERIES FROM CHINA

Abstract Background and Aims Belimumab (BLM) has been approved for the treatment of active systemic lupus erythematosus (SLE) and active lupus nephritis (LN). Multitarget therapy (MT) consisting of tacrolimus (FK506), mycophenolate mofetil (MMF), and steroid has been proved that can provide good curative effect as induction therapy for LN. Because of the limitations of BLM's phase III clinical trails, the exact curative effect in severe active LN of BLM is not clear yet. To assess the safety and generate preliminary efficacy data on MT followed by BLM for severe active Chinese LN patients, a case series were investigated. Method Six patients with severe active LN were reported. Among the 6 patients, 2 were treated with MT followed by BLM infusions, 2 were treated with MMF / (FK506) followed by BLM infusions, and 2 were treated with MT. BLM was given 10 mg/kg every 2 weeks for 3 times, then every 4 weeks till Week 24. Primary renal response index, SLEDAI, and safety data were analyzed. Results The patients affected by LN ISN/RNP Class III/IV±V with high disease activity are 3 de no LN and 3 refractory LN (each regimen included 1 de no LN and 1 refractory LN). At baseline, the SLEDAI score were 15,20,17,16,15,15 respectively. 4 of the 6 patients (case 1,case 2,case 3, and case 5) accepted intravenous (IV) methylprednisolone, followed by MT/MMF/FK506 after admission. The initial oral prednisone was 30-45 mg/day. Within 2 weeks of starting treatment, IV BLM was introduced. At Week 24, the SLEDAI score decreased to 2,8,8,10,8,10 respectively. 2 patients accepted BLM and MT achieved complete renal remission, and the other 4 patients achieved partial renal remission (Fig. 1). MT and BLM therapy reduced SLEDAI more rapidly than MMF/FK 506 +BLM or MT (Fig. 2). Prednisone was reduced to 10-15 mg/d. No adverse events occurred. Conclusion The addition of BLM to basic immunosuppressants was effective and safe for severe active LN. The BLM and MT regimen seems to lead a faster and more pronounced remission. Further prospective clinical studies with larger samples are needed to evaluate the benefits of belimumab combined with MT in severe active LN.

The Value of Lipocalin-2 in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune multisystem disease predominantly affecting women in the childbearing period. The majority of the pathology in SLE is related to deposits of immune complexes in various organs, which trigger complement and other mediators of inflammation. SLE is characterized by a very large spectrum of clinical manifestations accompanied by prototypic abnormalities of the immune system. Methods: This study was conducted on thirty SLE patients who were diagnosed according to the American College of Rheumatology (ACR) revised criteria. The patient was selected from the outpatient clinic of Rheumatology and Rehabilitation of Ain Shams University Hospital. Fifteen subjects, matched for age and sex, were included in the study and served as a control group. Comparison of quantitative variables between the study groups was done using the Kruskal Wallis analysis of variance (ANOVA) test with Mann Whitney U test for independent samples as posthoc multiple 2-group comparisons. A probability value (p-value) less than 0.05 was considered statistically significant. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows. Results and Discussion: Our results come in agreement with the study done by Farzaneh and his colleagues in 2013, who studied fifty-two lupus patients; urinary lipocalin-2 levels in LN patients were significantly higher than those in non-LN patients. Also, our results were in accordance with the study done by Hammad, who studied 33 children with active SLE (22 with and 11 without LN) and compared them with 15 matched controls. Levels of urinary NGAL were higher in patients with LN than those without LN. These findings come in consistent with previous work done by Youssef and his co-worker in 2015, who studied 44 SLE patients and divided them into two groups, group I (twenty-two patients with LN) and group II (twenty-two patients without LN), the urinary lipocalin-2 had the highest mean levels in LN patients (group I) compared to group II and controls with a statistically significant difference. Also, between SLE patients without nephritis (group II) and controls. Conclusions: In this study, urinary lipocalin-2 was significantly higher in the SLE patients compared to the control group, and the lupus nephritis patients, when compared to the patients with SLE without nephritis,showed significantly higher levels of urinary lipocalin-2. The significant association of the urinary lipocalin-2 with the renal SLEDAI shows that urinary lipocalin-2 can be an early biomarker to diagnose patients with lupus nephritis and to detect renal disease activity.

Performance of Clinical and Biochemical Parameters in Identifying Renal Histopathology and Predictors of One-Year Renal Outcome in Lupus Nephritis-A Single Centre Study from India.

Objectives: To assess the performance of clinical and biochemical parameters in identifying renal histopathology. To assess the performance of a combination of demographic, clinical, serological and histopathological parameters in determining renal response at one year. Methods: Data of biopsy-proven (ISN/RPS-2003 criteria) Lupus Nephritis (LN) were extracted from the institute database. Demographic, clinical and biochemical parameters at the time of biopsy were noted, and their associations with histopathological class, activity and chronicity scores were evaluated. Follow-up data at one year were collected. Complete, partial or no response (CR, PR, NR) for renal outcomes at one year and the predictors of NR were assessed. Results: Out of the 333 renal biopsies, 240 (71.8%) were Class III/IV. More patients with Class III/IV LN had hypertension (52.1%) and low eGFR (p < 0.001). Among Class III/IV, AS correlated weakly with UPCR (r = 0.31, p < 0.01), eGFR (r = -0.172; p < 0.01) and CS with eGFR (r = -0.212; p < 0.01). The presence of either hypertension, UPCR > 0.5 g/day, active urinary sediments or serum creatinine >1.3 g/dL had a sensitivity of >96% and specificity of <9% in detecting proliferative LN, crescents, interstitial inflammation and chronicity. NR was higher in males (aOR:3.9, 95% CI:1.4-11.0, p < 0.001), those with abnormal baseline creatinine (aOR: 1.9, 95% CI: 1.1-3.2, p < 0.001), higher renal SLEDAI (p < 0.05), higher AS, CS (p < 0.001) and interstitial inflammation (p < 0.005). In the binary logistic regression, the combination of male sex, baseline creatinine, UPCR and CS performed best in predicting NR (AUC: 0.762; 95% CI: 0.684-0.840, p < 0.001). Conclusions: Clinical and biochemical parameters alone have a poor specificity in identifying renal histopathology. A combination of demographic, clinical and histopathology parameters can better predict renal outcomes at one year.

Validity of immunoglobulin-binding protein 1 as a biomarker for lupus nephritis.

Lupus nephritis (LN) is a major issue that adds a burden on patients with systemic lupus erythematosus (SLE). Immunoglobulin-binding protein 1 (IGBP1) is identified as a phosphoprotein that has been recently reported to be linked to the B-cell receptor complex and regulates differentiation, proliferation, apoptosis, and tolerance of B cells. Its diagnostic and/or prognostic role in LN has been highlighted only recently. This study aims to evaluate the relation between serum IGBP1 and SLE disease activity and/or renal activity and to investigate the validity of IGBP1 as a biomarker for LN. 96 participants were enrolled and divided into three groups: nephritis, nonnephritis, and control groups. The patients with SLE were diagnosed according to the Systemic Lupus International Collaborating Clinics classification (SLICC) criteria. The serum IGBP1 level was assayed using an enzyme-linked immunosorbent assay (ELISA). Assessments were conducted using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k) and renal biopsy for LN patients. The nephritis and nonnephritis groups had higher IGBP1 levels than the controls; the nephritis group had the highest serum IGBP1 levels (p < .001). Significant correlations were found between IGBP1 levels and proteinuria (r = 0.568, p = .001) and renal SLEDAI (r = 0.475, p = .006) in the nephritis group; on the other hand, the correlation of serum IGBP1 levels with SLEDAI-2K was non-significant for both groups (nephritis and nonnephritis groups). The IGBP1 levels were significantly different among histopathologic classes (p < .001), with class V showing the highest level. Moreover, it showed a significant positive correlation with the pathologic activity index. Compared with renal SLEDAI for identifying active renal affection in patients with SLE, the serum IGBP1 level with a cut-off value of 547.45ng/mL is a valid biomarker for detecting active nephritis with 93.8% sensitivity and 96.9% specificity. The serum IGBP1 levels were high in patients with LN and were positively correlated with the pathologic activity index. The serum IGBP1 level of 547.45ng/mL is a valid biomarker for detecting active nephritis. Thus, we recommend that clinicians monitor the serum IGBP1 level of patients with SLE to detect LN.

Serum cystatin C and βeta-2 microglobulin as potential biomarkers in children with lupus nephritis.

In this study, we aimed to assess serum levels of Cystatin C (Cys C) and beta-2 microglobulin (β2M) in juvenile systemic lupus erythematosus (JSLE) patients and to investigate their role as potential biomarkers of lupus nephritis (LN) and overall disease activity. Between December 2018 and November 2019, a total of 40 patients with JSLE (11 males, 29 females; mean age: 12.6±2.5 years; range, 7.5 to 16 years) and 40 age- and sex-matched controls (10 males, 30 females; mean age: 12.3±2.4 years; range, 7 to 16 years) were included in this study. Serum (s) Cys C and β2M levels were compared between the groups. The SLE Disease Activity Index (SLEDAI-2K), the renal SLEDAI (rSLEDAI), and the Renal Damage Index were used. JSLE patients had significantly elevated mean sCyc C and sβ2M levels (1.4±0.8 mg/mL and 2.8±0.9 mg/mL, respectively) compared to the controls (0.6±0.1 mg/mL and 2.0±0.2 mg/mL, respectively; p<0.00). The mean sCys C and sβ2M levels were significantly higher in the LN group, compared to non-LN patients (1.8±0.7 mg/mL and 3.1±1.0 mg/mL, respectively vs. 0.8±0.3 mg/mL and 2.4±0.6 mg/mL, respectively; p=0.002 and p=0.02, respectively). The sCys C levels had significant positive correlations with erythrocyte sedimentation rate (r=0.3, p=0.05), serum creatinine (r=0.41, p= 0.007), 24-h urinary protein (r=0.58, p<0.001), anti-double stranded deoxyribonucleic acid antibodies titers (r=0.55, p=0.002), extra-renal SLEDAI scores (r=0.36, p=0.04), rSLEDAI (r=0.46, p=0.002), and renal class (r=0.7, p=0.0001). Serum β2M levels were significantly negatively correlated with complement 4 levels (r=-0.31, p=0.04) and significantly positively correlated with extra-renal SLEDAI scores (r=0.3, p=0.05). These findings confirm that sCys C and sβ2M levels are increased in JSLE patients in association with the overall active disease. However, sCys C level may act as a promising non-invasive biomarker for predicting kidney disease activity and biopsy classes in children with JSLE.

Low serum uromodulin levels and their association with lupus flares.

BackgroundOnly two previous studies in systemic lupus erythematosus (SLE) patients have identified that the blood concentrations of uromodulin are lower in nephritis. However, none of them had evaluated whether a low serum uromodulin adjusted by the glomerular filtration rate (sUromod/eGFR index) contributed to identify patients in risk of lupus nephritis (LN) using multivariable models.AimTherefore, this study aimed two objectives to evaluate the association between low serum uromodulin levels and low sUromod adjusted by eGFR with renal flares in SLE excluding effects of potential confounders in multivariable analyses; and to identify the value of low sUmod and low sUmod/eGFR index as a potential diagnostic marker of LN.Patients and methodsDesign: Cross-sectional study. SLE patients (n = 114) were investigated for lupus flare with renal SLEDAI. Two groups: a) SLE with renal flare (renal-SLEDAI≥4, n = 41) and b) SLE non-renal flare (renal SLEDAI<4, n = 73). SLE patients were evaluated by other indices including a global disease activity index (SLEDAI) and SLICC renal disease activity score. Serum uromodulin levels (ng/mL) were quantified by ELISA. Serum uromodulin was adjusted by eGFR (sUromod/eGFR index). Cutt-offs of low sUromodulin and low sUromod/eGFR index were computed, ROC curves were performed and values of diagnostic tests were obtained. Multivariable logistic regression models were performed to identify if low sUromod/eGFR index is associated to renal flares.ResultsLow serum uromodulin and low sUromod/eGFR index correlated to high scores of renal-SLEDAI, SLICC-renal and proteinuria. SLE patients with a renal flare had lower uromodulin levels compared to SLE patients without renal flare (p = 0.004). After adjusting by potential confounders, the low sUromod/eGFR index (<0.80 ng/mL) increased the risk of a renal flare (OR, 2.91; 95%CI, 1.21 to 6.98; p = 0.02).ConclusionsWe propose the low sUromod/eGFR index as a potential new marker of renal disease activity in SLE.

Exploring urine:serum fractional excretion ratios as potential biomarkers for lupus nephritis.

ObjectivesThe goal of this exploratory study is to determine if urine:serum fractional excretion ratios can outperform the corresponding urinary biomarker proteins in identifying active renal disease in systemic lupus erythematosus (SLE).MethodsThirty-six adult SLE patients and twelve healthy controls were examined for serum and urine levels of 8 protein markers, namely ALCAM, calpastatin, hemopexin, peroxiredoxin 6 (PRDX6), platelet factor 4 (PF4), properdin, TFPI and VCAM-1, by ELISA. Fractional excretion of analyzed biomarkers was calculated after normalizing both the urine and serum biomarker levels against creatinine. A further validation cohort of fifty SLE patients was included to validate the initial findings.ResultsThe FE ratios of all 8 proteins interrogated outperformed conventional disease activity markers such as anti-dsDNA, C3 and C4 in identifying renal disease activity. All but VCAM-1FE were superior to the corresponding urine biomarkers levels in differentiating LN activity, exhibiting positive correlation with renal SLEDAI. ALCAMFE, PF4FE and properdinFE ratios exhibited the highest accuracy (AUC>0.9) in distinguishing active LN from inactive SLE. Four of the FE ratios exhibited perfect sensitivity (calpastatin, PRDX6, PF4 and properdin), while ALCAMFE, PF4FE and properdinFE exhibited the highest specificity values for active LN. In addition, several of these novel biomarkers were associated with higher renal pathology activity indices. In the validation cohort ALCAMFE, PF4FE and properdinFE once again exhibited higher accuracy metrics, surpassing corresponding urine and serum biomarkers levels, with ALCAMFE exhibiting 95% accuracy in distinguishing active LN from inactive SLE.ConclusionsWith most of the tested proteins, urine:serum fractional excretion ratios outperformed corresponding urine and serum protein measurements in identifying active renal involvement in SLE. Hence, this novel class of biomarkers in SLE ought to be systemically evaluated in larger independent cohorts for their diagnostic utility in LN assessment.

Urinary CD163 is a marker of active kidney disease in childhood-onset lupus nephritis.

The objective of this study was to evaluate the utility of urine CD163 for detecting disease activity in childhood-onset SLE (cSLE) patients. Sixty consecutive pediatric patients fulfilling four or more ACR criteria for SLE and 20 healthy controls were recruited for testing of urinary CD163 using ELISA. SLE disease activity was assessed using the SLEDAI-2K. Urine CD163 was significantly higher in patients with active LN than inactive SLE patients and healthy controls, with receiver operating characteristics area under the curve values ranging from 0.93 to 0.96. LN was ascertained by kidney biopsy. Levels of CD163 significantly correlated with the SLEDAI, renal SLEDAI, urinary protein excretion and C3 complement levels. Urine CD163 was also associated with high renal pathology activity index and chronicity index, correlating strongly with interstitial inflammation and interstitial fibrosis based on the examination of concurrent kidney biopsies. Urine CD163 emerges as a promising marker for identifying cSLE patients with active kidney disease. Longitudinal studies are warranted to validate the clinical utility of urine CD163 in tracking kidney disease activity in children with lupus.

Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios.

IntroductionThere is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN.MethodsThis was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment.ResultsMCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66–0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone.ConclusionMCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.

The relationship between serum A proliferation-inducing ligand and B-cell activating factor levels with disease activity and organ involvement in systemic lupus erythematosus.

We aim to investigate the association between serum B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) levels with disease activity and clinical findings in SLE patients. Seventy-nine patients with SLE and 27 healthy controls were included into the study. Serum BAFF and APRIL levels were measured by using ELISA. In 19 patients with active disease at the time of the assessment, BAFF/APRIL levels were reassessed after 6months of follow-up and disease activity was evaluated by using SLEDAI-2K. The relationship between renal histopathology index scores and lupus nephritis (LN) classes with serum BAFF/APRIL levels was examined in 16 patients who had recent renal involvement and underwent biopsy during the study. Although both BAFF/APRIL levels were higher in patients with SLE compared to the control group (p < 0.001), no correlation was found between BAFF/APRIL levels and SLEDAI scores. Serum BAFF levels were higher in patients with renal disease activity (p = 0.01), and there was a significant correlation between APRIL levels and proteinuria (r = 0.42, p = 0.02). A weak inverse correlation was observed between BAFF and C3 levels (r = 0.25, p = 0.02). No correlation was found between BAFF/APRIL levels and renal SLEDAI scores, renal histopathology, activity, and chronicity index scores. In the active disease group after treatment, there was no significant change in serum BAFF levels, but a significant increase in serum APRIL levels was observed. These results suggest that both cytokines are involved in the pathogenesis of SLE and that serum BAFF can be valuable as a biomarker in SLE especially in patients with renal activity.

Serum and urinary galectin-9 and C-X-C motif chemokine ligand 10.

Systemic lupus erythematosus (SLE) is characterized by a type I interferon (IFN) signature, and traditional methods for its measurement like gene expression analysis are cumbersome for routine use. Thus, we aimed to study galectin-9 as a biomarker and compared it with a validated marker, C-X-C motifchemokine ligand 10(CXCL-10). Ninety-seven patients with SLE (26 years; 89 females) were included and stratified based on renal involvement and activity into - active (SLEDAI > 4) renal (35), active non-renal (32) and inactive renal subgroups (30) along with 20 healthy controls (HC, 25 years; 15 females). The median disease duration was 24months (6-48), and SLEDAI 2K was 9 (2-15). Serum and urine galectin-9 and CXCL-10 levels were measured by ELISA. Urine levels were normalized with spot urine creatinine values. Follow-up serum and urine galectin-9 levels were measured for those in the active renal group at 6months. Patients with SLE had higher serum galectin-9 (5.6 vs 1.7 μg/mL, p = .0001) but not urine galectin-9 (0.52 vs 0.32 μg, p = .7) levels as compared to HC. Serum galectin-9 but not urine galectin-9 was higher in patients with active as compared to inactive lupus (12.9 - active renal, 16.7 - active non-renal vs 3.57 μg/mL, p = .04 and .005). Serum CXCL-10 (0.16 vs 0.05, p = .01) and urine CXCL-10 (0 vs 0, p = .01) were both significantly higher in the SLE group as compared with HC. Serum but not urine CXCL-10 was higher in the active as compared to inactive lupus (0.2 - active renal, 0.3 - active non-renal vs 0.08 μg/mL, p = .9 and .02). Serum galectin-9 showed a modest correlation with CXCL-10 0.4 (0.2-0.6), whereas none was found between their urine levels.Serum galectin-9 and CXCL-10 showed a moderate positive correlation with SLEDAI 2K. Serum galectin-9 showed a greater AUC than CXCL-10 (0.77 vs 0.67) in differentiating active from inactive SLE, and both tested together had the best AUC of 0.82. However, urinary levels had no association with SLEDAI 2K or renal SLEDAI. In a subset of patients with active renal disease, serum galectin-9 but not urine levels declined significantly after 6months. Serum galectin-9 is a good marker of lupus activity; however, it does not differentiate between active renal and active non-renal disease. It performs slightly better than CXCL-10. Urinary galectin-9 does not reflect renal activity.

MO277THE RATIO OF NEUTROPHIL TO LYMPHOCYTE AS A POTENTIAL MARKER OF CLINICOPATHOLOGICAL ACTIVITY FOR SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract Background and Aims The ratio of neutrophils to lymphocytes (NLR) is a novel inflammatory factor that is elevated in systemic lupus erythematosus (SLE) and related to disease activity. However, the relationship between NLR and renal pathological manifestations in patients with lupus nephritis (LN) has not been studied. Method In this retrospective study, 240 SLE patients were recruited. 186 patients with renal involvement and 124 LN patients underwent renal biopsy. In the meanwhile, control groups included 125 chronic kidney disease (CKD) patients and 125 healthy volunteers. Patients with SLE disease activity 2000 (SLEDAI-2K) &amp;gt;9 and ≤ 9 were defined as severely active and mildly active, respectively. Clinical parameters and pathological data were collected. The correlations between NLR and clinicopathological features were analyzed. Results The NLR of SLE group was significantly higher than that of the sex-age matched control groups. Patients with nephritis had higher NLR levels than those without nephritis [2.88(1.81,4.32) vs. 2.43(1.55,3.90), P=0.044; Figure 1]. Increased NLR was observed in severely active group compared to mildly active group [3.00(1.84,4.28) vs.2.36(1.61,3.51), P=0.020; Figure 1]. NLR was significantly positively related with SLEDAI score (r=0.131, P=0.043), Renal SLEDAI score (r=0.173, P=0.023), C-reactive protein (CRP; r=0.213, P=0.002), 24-hour urine protein (r=0.274, P&amp;lt;0.001; Figure 2A), renal activity index (AI; r=0.192, P=0.033), cellular crescents (r=0.274, P=0.006) and tubular atrophy (r=0.226, P=0.011), and negatively correlated with serum albumin (r=-0.187, P=0.004; Figure 2A). Based on the receiver operating characteristic (ROC) curve, the best NLR cut-off value to predict severe activity and cellular crescents was 2.19 and 3.16, respectively. The ability of NLR to differentiate severely active from mildly active SLE was stronger than CRP and weaker than C3 (Figure 3A). The ability of NLR to predict cellular crescents was better than C3, but not superior to SLEDAI and RSLEDAI. Interestingly, the ROC fitted by NLR and RSLEDAI had a higher AUC and sensitivity [AUC=0.75(0.66,0.84), sensitivity=82.6%, specificity=63.6%; Figure 3B]. Conclusion NLR was a non-invasive and potential inflammatory factor to evaluate clinical and renal pathological activity in patients with SLE.

Elevated urinary IL-36γ in patients with active lupus nephritis and response to treatment

IL-36 is a new member of the IL-1 family with pro-inflammatory properties. Serum levels of IL-36 are elevated in patients with Systemic Lupus Erythematosus (SLE). However, no data is available on urinary levels of IL-36 in Lupus Nephritis (LN). In psoriasis expression of IL-36 is site specific and expressed in skin. Hence, we studied urinary levels of IL-36 cytokines in SLE patients. A total of 196 patients with SLE [97 active LN patients (ALN), 42 inactive LN (ILN) and 57 active lupus patients with no renal involvement (ANR)] and 25 healthy subjects were recruited for the study after obtaining informed consent. Urinary and plasma IL-36α, IL-36γ and IL-36Ra levels were measured by ELISA. Out of 196 patients 178 were females. Urinary IL-36γ levels in SLE patients [0(14.3) pg/ml] were significantly higher than healthy controls [0(0) pg/ml, (P < 0.01)]. Patients with ALN [0(40.6) pg/ml] had significantly higher IL-36γ when compared to ANR [0(0) pg/ml] as well as ILN [0(0) pg/ml]. Urinary IL-36γ levels in ALN patients had a fair correlation with renal SLEDAI (r = 0.26, P = 0.004).The levels reduced significantly post 3 months in patients with ALN. No inverse relationship was noted between IL-36Ra and IL-36α/IL36γ levels. Urinary IL-36γ is produced locally in kidney, correlates with renal disease activity and reduces upon treatment, suggesting that it may have a role in pathogenesis of LN.

Urinary TWEAK; Diagnostic and Prognostic Biomarker in Evaluating Lupus Nephritis Case Control Study

Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that belongs to the TNF-ligand superfamily. Objective: To evaluate the ability of urinary TWEAK (uTWEAK) to diagnose lupus nephritis (LN) and its correlation with activity and chronicity index. Patients and Methods: This study was carried out on 75 individuals, 50 SLE patients, fulfilling the SLICC revision of the ACR classification criteria for SLEand25 age and sex matched apparently healthy control subjects. Patients were assessed by SLE disease activity index (SLEDAI-2K) score. Renal biopsy were done for SLE patients who have confirmed proteinuria >0.5 g in 24-hour urine samples or active urinary sediment or inexplicable decrease in renal function. UrinaryTWEAK levels were measured by ELISA. Results: uTWEAK level showed a highly statistical significant difference among groups (P<0.001). There was direct highly significant correlations between uTWEAK and total (t)SLEDAI (r=0.58, P< 0.001) and renal (r)SLEDAI (r=0.73, P<0.001). uTWEAK hadsignificant association with the presence of proliferative GN (Class III, IV) (p= 0.003). At cutoff point ≥ 9.9 pg/mg Cr, uTWEAK had sensitivity of 76% and a specificity of 60 % to diagnose SLE patients with nephritis. At cutoff point of ≤ 14.9 pg/mg Cr, the uTWEAK level had a sensitivity of 88% and a specificity of 76% to predict good response to treatment in LN patients. Conclusion: We concluded that uTWEAK is a candidate biomarker for evaluating LN. It possesses numerous properties that make it suitable for assessment of LN activity and prognosis.

Urinary TWEAK; Diagnostic and Prognostic Biomarker in Evaluating Lupus Nephritis Case Control Study

Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that belongs to the TNF-ligand superfamily. Objective: To evaluate the ability of urinary TWEAK (uTWEAK) to diagnose lupus nephritis (LN) and its correlation with activity and chronicity index. Patients and Methods: This study was carried out on 75 individuals, 50 SLE patients, fulfilling the SLICC revision of the ACR classification criteria for SLEand25 age and sex matched apparently healthy control subjects. Patients were assessed by SLE disease activity index (SLEDAI-2K) score. Renal biopsy were done for SLE patients who have confirmed proteinuria >0.5 g in 24-hour urine samples or active urinary sediment or inexplicable decrease in renal function. UrinaryTWEAK levels were measured by ELISA. Results: uTWEAK level showed a highly statistical significant difference among groups (P<0.001). There was direct highly significant correlations between uTWEAK and total (t)SLEDAI (r=0.58, P< 0.001) and renal (r)SLEDAI (r=0.73, P<0.001). uTWEAK hadsignificant association with the presence of proliferative GN (Class III, IV) (p= 0.003). At cutoff point ≥ 9.9 pg/mg Cr, uTWEAK had sensitivity of 76% and a specificity of 60 % to diagnose SLE patients with nephritis. At cutoff point of ≤ 14.9 pg/mg Cr, the uTWEAK level had a sensitivity of 88% and a specificity of 76% to predict good response to treatment in LN patients. Conclusion: We concluded that uTWEAK is a candidate biomarker for evaluating LN. It possesses numerous properties that make it suitable for assessment of LN activity and prognosis.

Dermatologic Manifestations, Histologic Features and Disease Progression among Cutaneous Lupus Erythematosus Subtypes: A Prospective Observational Study in Asians.

IntroductionCutaneous manifestations are central to the primary diagnosis of systemic lupus erythematosus (SLE). However, information on the clinical, histopathologic, and direct immunofluorescence (DIF) features among subtypes of cutaneous lupus erythematosus (CLE), as well as longitudinal prospective observational study to evaluate the natural history and the progression to SLE, is lacking among Asians. Our objectives are to summarize the differences in the clinical, histopathologic, and DIF characteristics and serological profiles between various subtypes of CLE, and to provide its natural history and the association with disease activity in our Asian population.MethodsA prospective observational study on CLE patients was performed between May 2016 and May 2020. Patients underwent full physical/dermatologic examination, skin biopsy for histology, and DIF. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores and laboratory data were evaluated. Time schedule and characteristics for resolution and/or the disease progression to SLE were recorded in subsequent follow-ups.ResultsOf 101 biopsy-proven CLE patients, 25 had acute CLE (ACLE), 8 had subacute CLE (SCLE), 39 had chronic CLE (CCLE) only, 22 had CCLE with SLE, and 7 had LE-nonspecific cutaneous lesions only. Patients with exclusive CLE showed lower female preponderance, serological abnormalities, and correlation to systemic disease. However, when CLE was accompanied with any LE-nonspecific cutaneous manifestations, they were associated with high antinuclear antibody (ANA) titer, renal, hematologic, joint involvement, and greater SLEDAI score. Of 207 biopsy sections, SCLE/CCLE regardless of systemic involvement showed significantly higher percentage of superficial/deep perivascular and perieccrine infiltration than ACLE. On DIF, deposition of multiple immunoreactants was associated with higher systemic disease. Approximately 10% of CLE-only patients later developed SLE but had mild systemic involvement.ConclusionOur findings support that each CLE subtype has a diverse and unique character. Comprehensive understanding of the differences among CLE subtypes is important for achieving the correct diagnosis and providing appropriate disease monitoring and management.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-020-00471-y.

Lupus Nephritis: Role of Serum Complement Levels as Prognostic Marker

Background: Lupus Nephritis (LN) is one of the most common and serious manifestations in Systemic Lupus Erythematosus (SLE) patients that causes significant morbidity and mortality. Certain biomarkers for LN are sometimes able to assess treatment response of lupus nephritis. Objective: To compare serum complement levels (C3 &amp; C4) as markers of treatment response of LN and their relation to the LN class in renal biopsy. Methods: This prospective observational study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2018 to August 2019. Twenty seven patients who were diagnosed with lupus nephritis after kidney biopsy were included in this study. Serum complement levels (C3 &amp; C4), 24 hours urinary total protein (24-hr UTP) and anti-double-stranded DNA (anti-ds DNA) were measured in all patients at baseline, 3 months and 6 months after treatment. These biomarker values before and after treatment were compared between the treatment response and non response groups. Results: Serum C3 levels were significantly different in patients of proliferative lupus nephritis (Class III &amp; Class IV) than non proliferative lupus nephritis (Class V) at baseline (0.47 ± 0.32 vs0.89 ± 0.43g/l, p = 0.009) and levels changed significantly 6 months after treatment (p &lt;0.001) and likewise for Serum C4 levels (0.10 ± 0.06 vs0.24 ± 0.26g/l, p = 0.040). Serum C3 levels were also found to correlate significantly with SLEDAI and renal SLEDAI. No significant difference was observed for 24-hr UTP levels at baseline between remission and non-remission groups. Conclusion: Serum C3 &amp; C4 levels may be utilized as serological biomarkers to predict and monitor the treatment response of lupus nephritis.