Review: New Biomarkers Explored in SLE, but Need Exists for More Validation

A range of new non-serum biomarkers have been identified in recent years, but the authors of a new review urge caution until those markers are further validated.

A number of recent reports have suggested potentially promising biomarkers for systemic lupus nephritis (SLE), but the authors of a new review article caution that insufficient work has been done to corroborate those studies.

Writing in the journal Current Opinion in Rheumatology, corresponding author Ioannis Parodis, MD, PhD, of Sweden’s Karolinska University Hospital, and colleagues explained that the heterogeneity of SLE and the expanding range of treatment options have created an added need for reliable biomarkers.

“The recent approvals of new targeted therapies for SLE and the increasing awareness of the long-term adverse effects of glucocorticoids have necessitated optimization of surveillance and treatment evaluation,” Parodis and colleagues wrote.

Historically, efforts at developing biomarkers have focused on serum biomarkers, but the investigators said other types of potential biomarkers, such as markers from urine and cerebrospinal fluid (CSF), have recently been investigated.

The investigators decided to undertake a systematic review of recent articles related to biomarkers for SLE and lupus nephritis (LN). The search covered the period from January 2019 through November 2021. They limited their review to biomarkers that were studied in multiple papers or were validated in independent cohorts.

Parodis and colleagues found a number of intriguing possibilities. Urine activated leukocyte cell adhesion model (ALCAM) was found to be helpful in diagnosing both SLE and LN, but was also found to be potentially meaningful as a tool to monitor LN progression. CSF neutrophil gelatinase-associated lipocalin (NGAL) was reported to be particularly useful in identifying cases of neuropsychiatric SLE.

“NGAL is an acute-phase glycoprotein that is secreted also by cells other than neutrophils, including epithelial cells in renal tubules and neurons, and its expression increases during cellular stress,” the investigators said.

Like urine ALCAM, CD163 and vascular cell adhesion molecule 1 (VCAM-1) appear to be meaningful biomarkers for LN surveillance, according to the literature. Urine monocyte chemoattractant protein 1 and urine CD163 and NGAL were shown to be helpful in predicting treatment response in SLE and LN, respectively.

Lastly, serum complement component 3 and urinary VCAM-1 have been identified as predictors of long-term renal prognosis in LN.

Parodis and colleagues wrote that biomarkers are important not only because they can help assess individual cases, but also because they lead to greater understanding of the condition.

“Continuous technological advances have been empowering constantly evolving biomarker research within the field of SLE, which in turn contributes to a better understanding of its pathogenic mechanisms and optimized diagnostic and prognostic tools,” they wrote.

Yet, even as biomarker research has expanded beyond serum biomarkers, the investigators said not all of the research is sufficiently robust.

“Although selected molecules or a set of markers have emerged as promising biomarkers in selected cohorts in cross-sectional or single-center settings, validations in diverse SLE populations have in general been scarce, necessitating critical appraisal of the literature and further survey specifically designed to develop novel biomarkers, using proper methodology and statistical analysis,” they wrote.

The authors concluded that the lack of an effort to complete more validation studies includes a dearth of large-cohort studies, which they said could be a result of limited access to such populations.


Lindblom J, Mohan C, and Parodis I. Diagnostic, predictive and prognostic biomarkers in systemic lupus erythematosus: current insights. Curr Opin Rheumatol. 2022 Mar 1;34(2):139-149. doi:10.1097/BOR.0000000000000862

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