Frontiers in Immunology (Jan 2024)

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

  • Carolina Muñoz-Grajales,
  • Carolina Muñoz-Grajales,
  • Michelle L. Barraclough,
  • Michelle L. Barraclough,
  • Juan P. Diaz-Martinez,
  • Juan P. Diaz-Martinez,
  • Jiandong Su,
  • Jiandong Su,
  • Kathleen Bingham,
  • Mahta Kakvan,
  • Mahta Kakvan,
  • Roberta Pozzi Kretzmann,
  • Roberta Pozzi Kretzmann,
  • Maria Carmela Tartaglia,
  • Lesley Ruttan,
  • May Y. Choi,
  • Simone Appenzeller,
  • Sherief Marzouk,
  • Dennisse Bonilla,
  • Dennisse Bonilla,
  • Patricia Katz,
  • Dorcas Beaton,
  • Robin Green,
  • Dafna D. Gladman,
  • Dafna D. Gladman,
  • Joan Wither,
  • Joan Wither,
  • Joan Wither,
  • Zahi Touma,
  • Zahi Touma

DOI
https://doi.org/10.3389/fimmu.2023.1326751
Journal volume & issue
Vol. 14

Abstract

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ObjectiveCognitive 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.MethodsTwo 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.ResultsOf 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.ConclusionIn 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.

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