TY - JOUR
T1 - Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment
AU - Muñoz-Grajales, Carolina
AU - Barraclough, Michelle L
AU - Diaz-Martinez, Juan P
AU - Su, Jiandong
AU - Bingham, Kathleen
AU - Kakvan, Mahta
AU - Kretzmann, Roberta Pozzi
AU - Tartaglia, Maria Carmela
AU - Ruttan, Lesley
AU - Choi, May Y
AU - Appenzeller, Simone
AU - Marzouk, Sherief
AU - Bonilla, Dennisse
AU - Katz, Patricia
AU - Beaton, Dorcas
AU - Green, Robin
AU - Gladman, Dafna D
AU - Wither, Joan
AU - Touma, Zahi
N1 - Copyright © 2024 Muñoz-Grajales, Barraclough, Diaz-Martinez, Su, Bingham, Kakvan, Kretzmann, Tartaglia, Ruttan, Choi, Appenzeller, Marzouk, Bonilla, Katz, Beaton, Green, Gladman, Wither and Touma.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Humans
KW - Calgranulin A
KW - Calgranulin B
KW - Cognitive Dysfunction/diagnosis
KW - Lupus Erythematosus, Systemic/complications
KW - Matrix Metalloproteinase 9/metabolism
U2 - 10.3389/fimmu.2023.1326751
DO - 10.3389/fimmu.2023.1326751
M3 - Article
C2 - 38332909
SN - 1664-3224
VL - 14
SP - 1326751
JO - Frontiers in Immunology
JF - Frontiers in Immunology
ER -