Author Correction: Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities

Stanley, Samantha; Vanarsa, Kamala; Soliman, Samar; Habazi, Deena; Pedroza, Claudia; Gidley, Gabriel; Zhang, Ting; Mohan, Shree; Der, Evan; Suryawanshi, Hemant; Tuschl, Thomas; Buyon, Jill P.; Putterman, Chaim; Mok, Chi Chiu; Petri, Michelle; Saxena, Ramesh; Mohan, Chandra

doi:10.1038/s41467-020-16944-9

Cited by 6 publications

(5 citation statements)

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“…ALCAM expression was also up-regulated in the glomeruli and tubules of MRL/lpr lupus-like murine model (33). In recent high-throughput proteomic approaches, urine ALCAM showed promise in predicting LN activity in SLE patients (30). Further validation in two aSLE cohorts confirmed the higher urine ALCAM levels with significant correlations with total and renal SLEDAI scores (34,35).…”

Section: Discussionmentioning

confidence: 87%

“…Based on the correlation analysis (Figure 1B) and the unsupervised Bayesian network analysis (Figure 5), urine ALCAM is likely driving the biomarker potential of VCAM1 and PF4. Indeed, Bayesian analysis also identified urine ALCAM as a driving factor in dictating the expression profiles of other urine markers in aSLE (30). ALCAM, also known as cluster of differentiation-166 (CD-166) is a cell adhesion glycoprotein that is highly expressed on antigen-presenting cells and shows a fundamental role in mediating immune cell adhesion and migration, co-stimulation of T-cells and sustaining T cell activation.…”

Section: Discussionmentioning

confidence: 99%

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Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus

et al. 2022

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ObjectivesSerial kidney biopsy for repeat evaluation and monitoring of lupus nephritis (LN) in childhood-onset Systemic Lupus Erythematosus (cSLE) remains challenging, thus non-invasive biomarkers are needed. Here, we evaluate the performance of ten urine protein markers of diverse nature including cytokines, chemokines, and adhesion molecules in distinguishing disease activity in cSLE.MethodsEighty-four pediatric patients meeting ≥4 ACR criteria for SLE were prospectively enrolled for urine assay of 10 protein markers normalized to urine creatinine, namely ALCAM, cystatin-C, hemopexin, KIM-1, MCP-1, NGAL, PF-4, Timp-1, TWEAK, and VCAM-1 by ELISA. Samples from active renal (LN) and active non-renal SLE patients were obtained prior to onset/escalation of immunosuppression. SLE disease activity was evaluated using SLEDAI-2000. 59 patients had clinically-active SLE (SLEDAI score ≥4 or having a flare), of whom 29 patients (34.5%) were classified as active renal, and 30 patients (35.7%) were active non-renal. Twenty-five healthy subjects were recruited as controls.ResultsUrine concentrations of ALCAM, KIM-1, PF4 and VCAM-1 were significantly increased in active LN patients versus active non-renal SLE, inactive SLE and healthy controls. Five urine proteins differed significantly between 2 (hemopexin, NGAL, MCP1) or 3 (Cystatin-C, TWEAK) groups only, with the highest levels detected in active LN patients. Urine ALCAM, VCAM-1, PF4 and hemopexin correlated best with total SLEDAI as well as renal-SLEDAI scores (p < 0.05). Urine ALCAM, VCAM-1 and hemopexin outperformed conventional laboratory measures (anti-dsDNA, complement C3 and C4) in identifying concurrent SLE disease activity among patients (AUCs 0.75, 0.81, 0.81 respectively), while urine ALCAM, VCAM-1 and PF4 were the best discriminators of renal disease activity in cSLE (AUCs 0.83, 0.88, 0.78 respectively), surpassing conventional biomarkers, including proteinuria. Unsupervised Bayesian network analysis based on conditional probabilities re-affirmed urine ALCAM as being most predictive of active LN in cSLE patients.ConclusionUrinary ALCAM, PF4, and VCAM-1 are potential biomarkers for predicting kidney disease activity in cSLE and hold potential as surrogate markers of nephritis flares in these patients.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus

et al. 2022

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“…With the rapid development of single-cell RNA sequencing (scRNA seq) and its application in the profiling of genes associated with SLE or LN (164)(165)(166), more novel biomarkers or biomarker panels may be emerging. However, these gene expression data must be validated at the protein level before moving to biomarker detection in clinical settings.…”

Section: Biomarker Panels For Sle: the Destinationmentioning

confidence: 99%

Emerging Molecular Markers Towards Potential Diagnostic Panels for Lupus

et al. 2022

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Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease which can affect various tissues and organs, posing significant challenges for clinical diagnosis and treatment. The etiology of SLE is highly complex with contributions from environmental factors, stochastic factors as well as genetic susceptibility. The current criteria for diagnosing SLE is based primarily on a combination of clinical presentations and traditional lab testing. However, these tests have suboptimal sensitivity and specificity. They are unable to indicate disease cause or guide physicians in decision-making for treatment. Therefore, there is an urgent need to develop a more accurate and robust tool for effective clinical management and drug development in lupus patients. It is fortunate that the emerging Omics have empowered scientists in the discovery and identification of potential novel biomarkers of SLE, especially the markers from blood, urine, cerebrospinal fluids (CSF), and other bodily fluids. However, many of these markers have not been carefully validated for clinical use. In addition, it is apparent that individual biomarkers lack sensitivity or specificity. This review summarizes the sensitivity, specificity and diagnostic value of emerging biomarkers from recent studies, and discusses the potential of these markers in the development of biomarker panel based diagnostics or disease monitoring system in SLE.

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“…Moreover, these tests have been studied most in patients with lupus nephritis and their utility in detecting other manifestations of SLE is less clear. More comprehensive tools that integrate novel biomarkers, identified by longitudinal analyses of well-characterized cohorts and the use of new big data analytical techniques, such as machine learning, could be valuable for capturing disease activity and providing timely stratification of patients based on the unified pattern of dysregulated pathways (41,42). Transcriptomic studies have identified distinctive signatures in SLE blood samples that include type I interferons (IFN), as well as myeloid and B cell-related (plasma cell) signatures (43)(44)(45)(46).…”

Section: Challenges In Established Disease Disease Activitymentioning

confidence: 99%

“…Transcriptomic studies have identified distinctive signatures in SLE blood samples that include type I interferons (IFN), as well as myeloid and B cell-related (plasma cell) signatures (43)(44)(45)(46). Several studies also showed a correlation between these signatures and disease activity (42)(43)(44). Although a robust interferon gene signature (IGS) has been demonstrated in both blood and affected tissues of SLE patients (47), no apparent correlations have been found between the IGS and disease activity in longitudinal studies (46,48,49).…”

Section: Challenges In Established Disease Disease Activitymentioning

confidence: 99%

Current Status of the Evaluation and Management of Lupus Patients and Future Prospects

Yavuz

Lipsky

2021

Front. Med.

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The vastly diverse nature of systemic lupus erythematosus (SLE) poses great challenges to clinicians and patients, as well as to research and drug development efforts. Precise management of lupus patients would be advanced by the ability to identify specific abnormalities operative in individual patients at the time of encounter with the clinician. Advances in new technologies and bioinformatics have greatly improved the understanding of the pathophysiology of SLE. Recent research has focused on the discovery and classification of sensitive and specific markers that could aid early accurate diagnosis, better monitoring of disease and identification of appropriate therapy choices based on specific dysregulated molecular pathways. Here, we summarize some of the advances and discuss the challenges in moving toward precise patient-centric management modalities in SLE.

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Author Correction: Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cited by 6 publications

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Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus

Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus

Emerging Molecular Markers Towards Potential Diagnostic Panels for Lupus

Current Status of the Evaluation and Management of Lupus Patients and Future Prospects

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