AUTHOR=Wegener Maria Alexandra Bandehkhoda , Möller Sören , Olesen Mads Nikolaj , Madsen Jonna Skov , Sorensen Grith Lykke , Voss Anne , Asgari Nasrin 

TITLE=Microfibrillar-associated protein 4 interaction with inflammation and clinical characteristics in neuropsychiatric systemic lupus erythematosus

JOURNAL=Frontiers in Lupus

VOLUME=2

YEAR=2024

URL=https://www.frontiersin.org/journals/lupus/articles/10.3389/flupu.2024.1386256

DOI=10.3389/flupu.2024.1386256

ISSN=2813-6934

ABSTRACT=<sec><title>Objectives</title><p>Central nervous system (CNS) proteins such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are released into the body fluids following CNS injury. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein. Recently we reported expression of MFAP4 in CNS and alteration of levels in patients with acute neuroinflammation. We aimed to determine the levels of MFAP4 in a predominantly population-based cohort of systemic lupus erythematosus (SLE) patients, including neuropsychiatric SLE (NPSLE), and to evaluate MFAP4 as a marker of inflammation.</p></sec><sec><title>Methods</title><p>In total 208 SLE patients, 44 of those with NPSLE, and 50 age- and sex-matched healthy controls (HC) were recruited. MFAP4 was measured using AlphaLISA immunoassay. NfL, GFAP and a panel of inflammatory mediators were measured using Simoa HD-1 digital ELISA or a Luminex 200 instrument.</p></sec><sec><title>Results</title><p>MFAP4 levels were elevated in patients with NPSLE compared to patients with non-NPSLE (<italic>p</italic> = 0.031), more prominent in NPSLE patients with CNS involvement (<italic>p</italic> = 0.017). NfL and GFAP were higher in the total SLE cohort (<italic>p</italic> &lt; 0.001, <italic>p</italic> &lt; 0.001, respectively) as well as NPSLE subgroup (<italic>p</italic> &lt; 0.001, <italic>p</italic> &lt; 0.001, respectively), and in the subgroup of NPSLE patients with CNS involvement (<italic>p</italic> &lt; 0.001, <italic>p</italic> &lt; 0.001), compared to HC. NfL and GFAP levels correlated positively with MFAP4 in the NPSLE as well as the non-NPSLE subgroup (<italic>ρ</italic> = 0.44, <italic>p</italic> = 0.003, <italic>ρ</italic> = 0.25, <italic>p</italic> = 0.004). VEGF was reduced in NPSLE patients compared to HC (<italic>p</italic> = 0.015). MMP-9 was elevated in NPSLE compared to non-NPSLE (<italic>p</italic> = 0.048). Inflammatory markers including IFN-α, IL-6, IL-10 and TNF-α, were elevated in the NPSLE group compared to HC (<italic>p</italic> &lt; 0.001, <italic>p</italic> = 0.0026, <italic>p</italic> = 0.042, <italic>p</italic> = 0.007, respectively). In NPSLE patients the levels of MFAP4 correlated with TNF-α (<italic>p</italic> = 0.016) and IL-17 (<italic>p</italic> = 0.0044) and with markers of blood brain barrier (BBB) disruption MMP-7 (<italic>p</italic> = 0.005) and VEGF (<italic>p</italic> &lt; 0.001). In NPSLE patients with CNS manifestations MMP-3 and VEGF correlated with MFAP4 (<italic>p</italic> = 0.011, <italic>p</italic> = 0.0004, respectively).</p></sec><sec><title>Conclusion</title><p>Levels of MFAP4 correlated with NfL, GFAP and proinflammatory cytokines and in NPSLE additionally with markers of BBB disruption, suggesting that MFAP4 is a marker of inflammation and vascular re-organization. Correlation of NfL and GFAP with MFAP4 may reflect CNS tissue damage.</p></sec>