Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment.

Objective: Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI.
Methods: Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated.
Results: Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI.
Conclusion: In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.
Competing Interests: MT is Scientific advisor for Women’s Brain Project, Brain Injury Canada and PSP Canada and reports a relationship via clinical trials with Janssen, Biogen, Avanex, Green Valley and Roche. SA reports honoraria for lectures/speakers fees from GSK and AstraZeneca. DB serves Chair Methodology of the OMERACT Management Group. RG serves on the INS Board of Governors and Brain Injury Canada Scientific Advisory Committee. JW reports a relationship with honoraria for lectures from AstraZeneca, participation on the AstraZeneca Advisory Board, indirect support for meeting attendance/travel from multiples drug companies through Lupus 21st Century and indirect salary support from unrestricted funds given by Pfizer for a research chair in the Division of Rheumatology. ZT reports a relationship in the form of consulting fees from AstraZeneca, GlaxoSmithKline Inc, Merck, Ampel, Sarkana Pharma, AbbVie and UCB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Muñoz-Grajales, Barraclough, Diaz-Martinez, Su, Bingham, Kakvan, Kretzmann, Tartaglia, Ruttan, Choi, Appenzeller, Marzouk, Bonilla, Katz, Beaton, Green, Gladman, Wither and Touma.)