Anti‐dsDNA, anti‐nucleosome, anti‐C1q, and anti‐histone antibodies as markers of active lupus nephritis and systemic lupus erythematosus disease activity

Based on the recent evidence of association between hyperprolactinemia and systemic lupus erythematosus disease activity (SLEDAI), a study was conducted to analyze the association of hyperprolactinemia with lupus nephritis disease activity. In this cross-sectional study, the analysis was conducted on SLE patients who visited the University Kebangsaan Malaysia Medical Centre (UKMMC) Nephrology Clinic from August 2015 till February 2016. The disease activity was measured using the SLEDAI score, with more than 4 indicating active lupus nephritis. Basal resting prolactin level was analyzed in 43 patients with lupus nephritis, in 27.9% of them had raised serum prolactin. The median of serum prolactin level at 0 minutes was 19.91 ng/mL (IQR: 15.95-22.65 ng/ mL) for active lupus nephritis, which was significantly higher compared to the median of serum prolactin level of 14.34 ng/mL (IQR: 11.09-18.70 ng/mL) for patients in remission (p=0.014). The serum prolactin level positively correlated with SLEDAI (rhos: 0.449, p=0.003) and the UPCI level in lupus nephritis patients (rhos: 0.241, p=0.032). The results were reproduced when the serum prolactin was repeated after 30 minutes. However, the serum prolactin levels at 0 minutes were higher than those taken after 30 minutes (p=0.001). An assessment of serum IL-6 levels found that the active lupus nephritis patients had a higher median level of 65.91 pg/ mL (IQR: 21.96-146.14 pg/mL) compared to the in-remission level of 15.84 pg/mL (IQR: 8.38-92.84 pg/mL), (p=0.039). Further correlation analysis revealed that there was no statistical correlation between the interleukin (IL)-6 levels with serum prolactin, SLEDAI and other lupus nephritis parameters. An ROC curve analysis of serum prolactin at 0 minutes and serum prolactin after 30 minutes and IL-6 levels for prediction of SLE disease activity provided the cutoff value of serum prolactin at 0 minutes, which was 14.63 ng/mL with a sensitivity of 91.7% and specificity of 58.1% and AUC of 0.74 (p=0.015). This study concurred with the previous findings that stated that hyperprolactinemia is prevalent in SLE patients and correlated with clinical disease activity and UPCI level. The baseline of the fasting serum prolactin level was found to be a sensitive biomarker for the evaluation of lupus nephritis disease activity.

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

Egyptian Rheumatology and Rehabilitation ◽

10.1186/s43166-021-00064-3 ◽

2021 ◽

Vol 48 (1) ◽

Author(s):

Mervat E. Abdelazeem ◽

Marwa I. Abdelhaleem ◽

Rabab A. Mohamed ◽

Enas A. Abdelaleem

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Serum Levels ◽

Renal Diseases ◽

Systemic Lupus ◽

Active Lupus Nephritis ◽

Active Lupus

Abstract Background Systemic 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. Results DKK-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. Conclusion DKK-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.

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Serum and Circulatory Omentin mRNA Gene Expression as Predictive Markers of Systemic Lupus Erythematosus Disease Activity and Lupus Nephritis

The Egyptian Journal of Hospital Medicine ◽

10.21608/ejhm.2021.206850 ◽

2021 ◽

Vol 85 (2) ◽

pp. 3989-3996

Author(s):

Nearmeen M. Rashad ◽

Usama Khalil ◽

Mahmoud A. Sharafeddin ◽

Rehab M. Atef ◽

Marwa H.S. Hussien ◽

...

Keyword(s):

Gene Expression ◽

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Predictive Markers ◽

Systemic Lupus Erythematosus Disease ◽

Systemic Lupus ◽

Mrna Gene ◽

Mrna Gene Expression

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Urinary Soluble Alpha Chain of the Interleukin-2 Receptor as a Biomarker of Active Lupus Nephritis in Egyptian Children With Juvenile Systemic Lupus Erythematosus

Archives of Rheumatology ◽

10.46497/archrheumatol.2021.8001 ◽

2020 ◽

Author(s):

Waleed HASSAN ◽

Eman BEHIRY ◽

Marwa MAHGOUB

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Interleukin 2 ◽

Systemic Lupus ◽

Juvenile Systemic Lupus Erythematosus ◽

Interleukin 2 Receptor ◽

Egyptian Children ◽

Active Lupus Nephritis ◽

Active Lupus

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O004. Assessment of the impact of lupus nephritis on clinical, biological parameters, disease activity and mortality in pediatric Systemic Lupus Erythematosus

Rheumatology ◽

10.1093/rheumatology/keab723.003 ◽

2021 ◽

Vol 60 (Supplement_5) ◽

Author(s):

O Gacem ◽

L Labboun ◽

N Ayad ◽

Z Zeroual ◽

Z Arrada ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Renal Failure ◽

Chronic Renal Failure ◽

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Systemic Lupus Erythematosus Disease ◽

Systemic Lupus ◽

Pediatric Systemic Lupus Erythematosus ◽

The Impact

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Kidney involvement is one of the most frequent and severe manifestations of pediatric systemic lupus erythematosus (pSLE), seriously affecting the prognosis. It usually manifests as glomerulonephritis of varying severity. Objective: Knowledge of the correlation of lupus nephritis (LN) with clinical, biological, immunological parameters, disease activity and mortality in pediatric systemic lupus erythematosus is limited. This study aims to describe the impact of renal involvement with these different determinants. Methods This was a prospective, multicenter, descriptive 36-month study (January 2015 - December 2018) including patients less than 16 years of age with LN. The presence of LN was defined according to the American College of Rheumatology classification SLE criteria. The LN class was determined by renal biopsy and was classified according to the Morphology in Kidney International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2004 classification of lupus nephritis. The disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the use of which has been validated in children. Means, percentages and Chi-square tests were specified. P values less than 0.05 were considered statistically significant. Results We included 83 patients in this study. 37/83 patients (44.6%) developed LN with the following urinary signs: 92% of proteinuria (mean 3366.147 mg ± 2785.93 / 24h) including 2/3 of cases of nephrotic syndrome, 81% of hematuria, 14% of acute renal failure with significant reduction in glomerular filtration rate (average creatinine clearance of 32.42 ml / min) and 12% high blood pressure. Out of a total of 30 renal biopsies interpreted at disease diagnosis, 73.4% diffuse proliferative glomerulonephritis forms were observed: (III (30%), IV (36.7%) and VI (6, 7%)). Lupus nephritis were significantly correlated with hypocomplementemia in its C3 (P = 0.00002) and C4 (P = 0.00005) fraction, lymphopenia (P = 0.02), anti-DNA antibodies (P = 0.026), SLEDAI (P = 0.00001) and mortality (P = 0.03). The most frequently used induction drugs for LN classes III, IV and VI were pulsed intravenous methylprednisolone (500 mg daily for 3 doses) in combination with low dose intravenous cyclophosphamide (23%) in the short term (500 mg/m2/15 days X 6) followed by mycophenolate mofetil (28%) (600mg/ m2 in two daily doses) as maintenance treatment associated with a daily dose of oral glucocorticoids with a gradual decrease until reaching the minimum amount necessary to control the disease. All of our SLE patients with nephritis were treated with HCQ with a significant correlation with the decrease in SLEDAI. During the first two years of disease progression, the frequency of LN increased to 43/83 (51.8%) mainly in these severe forms: (IV (41.7%), V (2.8 %). The progression to chronic renal failure had a prevalence of 6, 9% (3/43) of cases; these were mainly patients with severe lupus nephritis (III, and IV) Conclusion Nephritis is a major risk factor for morbidity and mortality in pSLE; LN in children is most often proliferating and more active. The early diagnosis and management of kidney damage are the only guarantee of a good course and prevention of the progression of chronic renal failure. Keywords lupus nephritis; child; systemic lupus erythematosus; disease activity, mortality.

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Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus

Lupus ◽

10.1177/0961203319887799 ◽

2019 ◽

Vol 28 (14) ◽

pp. 1669-1677 ◽

Cited By ~ 3

Author(s):

R Kandane-Rathnayake ◽

J R Kent ◽

W Louthrenoo ◽

S -F Luo ◽

Y -JJ Wu ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Renal Damage ◽

Organ Damage ◽

Systemic Lupus ◽

Damage Accrual ◽

Active Lupus Nephritis ◽

Longitudinal Associations ◽

Active Lupus

Objective To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). Methods This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. Results Patients ( N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. Conclusion Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

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