Clinical disease activity and flare in SLE: Current concepts and novel biomarkers - PubMed (original) (raw)

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Clinical disease activity and flare in SLE: Current concepts and novel biomarkers

Aikaterini Thanou et al. J Autoimmun. 2021 May.

Abstract

Systemic lupus erythematosus (SLE) is a complex and heterogeneous systemic autoimmune disease associated with innate and adaptive immune dysregulation. SLE occurs primarily in females of childbearing age, with increased prevalence and severity in minority populations. Despite improvements in treatment modalities, SLE patients frequently experience periods of heightened disease activity and flare that can lead to permanent organ damage, increased morbidity, and early mortality. Such outcomes impair quality of life and inflict a significant socioeconomic burden. Predicting changes in SLE disease activity could allow for closer monitoring and preemptive treatment, but existing clinical, demographic and serologic markers have been only modestly predictive. Novel, proactive approaches to clinical disease management are thus critically needed. Panels of blood biomarkers can detect a breadth of immune pathway dysregulation that captures SLE heterogeneity and disease activity. Alterations in the balance of pro-inflammatory and regulatory soluble mediators have been associated with changes in clinical disease activity and are detectable several weeks prior to clinical flare occurrence. A soluble mediator score has been highly predictive of impending flare in both European American and African American SLE patients, and this score does not require a priori knowledge of specific pathway activation in the patient. We review current concepts of disease activity and flare in SLE, focusing on the potential of novel blood biomarkers to characterize and predict changes in disease activity. Measuring the disordered immune response in SLE in this way promises to improve disease management and prevent organ damage in SLE.

Keywords: Biomarkers; Clinical disease activity; Clinical disease flare; Cytokines; Forecasting; Systemic lupus erythematosus.

Copyright © 2021 Progentec Diagnostics, Inc. Published by Elsevier Ltd.. All rights reserved.

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Figures

Figure 1.

Figure 1.. Summary of altered soluble mediators in SLE patients associated with heightened clinical disease activity and risk of imminent clinical disease flare.

Inflammatory mediators significantly higher in SLE patients with impending disease flare (compared to NF/SNF and HC) are listed in red. Those mediators found to be higher in SLE patients compared to HC, but with levels variable (cohort-dependent) between SLE patients, are dashed. SLE patients with impending disease flare have increased innate (A) and adaptive (B) inflammatory mediators, including those from Th1, Th2, and Th17 pathways. In addition, inflammatory chemokines (C) and soluble TNFR superfamily members (D) are elevated in these patients. SLE patients who are in a period of non-flare (NF/SNF groups, compared to Pre-flare and HC) have higher regulatory mediators, including IL-10, TGF-β, and IL-1RA, listed in blue.

Figure 2.

Figure 2.. Models of altered soluble mediators and flare risk soluble mediator score (SMS) relative to changes in clinical disease activity (SELENA-SLEDAI) in SLE.

(A) Plasma levels of immune mediators are altered (increased or decreased), reflected in a flare risk SMS (blue dotted line, left y-axis) prior to changes in clinical disease activity (solid line, right y-axis). Prior to imminent clinical disease flare, pro-inflammatory mediators dominate (red profile), whereas regulatory mediators (blue profile) are more likely to be elevated after treatment (*) for clinical disease flare and during more stable (non-flare) periods of clinical disease activity. (B) Model of a flare risk SMS (blue dotted line, left y-axis) vs. clinical disease activity (black solid line, right y-axis) over time in a lupus patient with waxing/waning disease activity with clinical flares (red squares = times of clinical disease flare). (C) Model of a flare risk SMS (blue dotted line, left y-axis) vs. clinical disease activity (black solid line, right y-axis) over time in a lupus patient active disease, but no impending disease flare. (D) Model of a flare risk SMS (blue dotted line, left y-axis) vs. clinical disease activity (black solid line, right y-axis) over time in a lupus patient with quiescent or minimally active, stable clinical disease (no flare).

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