Laboratory and Neuroimaging Biomarkers in Neuropsychiatric Systemic Lupus Erythematosus: Where Do We Stand, Where To Go?

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-systemic involvement. Nervous system involvement in SLE leads to a series of uncommon and heterogeneous neuropsychiatric (NP) manifestations. Current knowledge on the underlying pathogenic processes and their subsequent pathophysiological changes leading to NP-SLE manifestations is incomplete. Several putative laboratory biomarkers have been proposed as contributors to the genesis of SLE-related nervous system damage. Alongside the laboratory biomarkers, several neuroimaging tools have shown to reflect the nature of tissue microstructural damage associated with SLE, and thus were suggested to contribute to the understanding of the pathophysiological changes and subsequently help in clinical decision making. However, the number of useful biomarkers in NP-SLE in clinical practice is disconcertingly modest. In some cases it is not clear whether the biomarker is truly involved in pathogenesis, or the result of non-specific pathophysiological changes in the nervous system (e.g., neuroinflammation) or whether it is the consequence of a concomitant underlying abnormality related to SLE activity. In order to improve the diagnosis of NP-SLE and provide a better targeted care to these patients, there is still a need to develop and validate a range of biomarkers that reliably capture the different aspects of disease heterogeneity. This article critically reviews the current state of knowledge on laboratory and neuroimaging biomarkers in NP-SLE, discusses the factors that need to be addressed to make these biomarkers suitable for clinical application, and suggests potential future research paths to address important unmet needs in the NP-SLE field.

Keywords: NP-SLE; biomarkers; magnetic resonance imaging; neuroimaging; neuropsychiatric systemic lupus erythematosus; systemic lupus erythematosus.

Figure 1

Types of biomarkers in NP-SLE.

Figure 2

Basis of Magnetization Transfer Imaging. (A) This technique is based on the application of off-resonance radiofrequency pulses. M₀: proton density image or intensity of voxels without saturation, M_s: Bound protons or intensity of voxels saturated. (B) Measurement of signal intensity with and without the application of these pulses allows the calculation of an index called the magnetization transfer ratio (MTR) which is defined as (M₀-M_s/M₀) × 100%. (C) MTR histogram: this technique takes a ratio of the two images on a voxel-by-voxel basis (brain pixels). (D) The histogram peak height (HPH), a MTR histogram-derived measure, accounts for the proportion of brain pixels at the most common MTR value. (A) partially adapted from Grossman et al. (61).

Figure 3

Examples of 3T FLAIR* imaging demonstrating the central vessel sign (arrows) in multiple sclerosis (left) but not in systemic lupus erythematosus (right). Figure adapted with permission from Maggi et al. (119).