| Autor: |
Wang, Angela A., Luessi, Felix, Neziraj, Tradite, Pössnecker, Elisabeth, Zuo, Michelle, Engel, Sinah, Hanuscheck, Nicholas, Florescu, Alexandra, Bugbee, Eryn, Ma, Xianjie I., Rana, Fatima, Lee, Dennis, Ward, Lesley A., Kuhle, Jens, Himbert, Johannes, Schraad, Muriel, van Puijenbroek, Erwin, Klein, Christian, Urich, Eduard, Ramaglia, Valeria |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 3/6/2024, Vol. 16 Issue 737, p1-16, 16p |
| Abstrakt: |
Anti-CD20 therapy to deplete B cells is highly efficacious in preventing new white matter lesions in patients with relapsing-remitting multiple sclerosis (RRMS), but its protective capacity against gray matter injury and axonal damage is unclear. In a passive experimental autoimmune encephalomyelitis (EAE) model whereby TH17 cells promote brain leptomeningeal immune cell aggregates, we found that anti-CD20 treatment effectively spared myelin content and prevented myeloid cell activation, oxidative damage, and mitochondrial stress in the subpial gray matter. Anti-CD20 treatment increased B cell survival factor (BAFF) in the serum, cerebrospinal fluid, and leptomeninges of mice with EAE. Although anti-CD20 prevented gray matter demyelination, axonal loss, and neuronal atrophy, co-treatment with anti-BAFF abrogated these benefits. Consistent with the murine studies, we observed that elevated BAFF concentrations after anti-CD20 treatment in patients with RRMS were associated with better clinical outcomes. Moreover, BAFF promoted survival of human neurons in vitro. Together, our data demonstrate that BAFF exerts beneficial functions in MS and EAE in the context of anti-CD20 treatment. Editor's summary: Depletion of B cells with anti-CD20 therapy is an effective therapy for relapsing-remitting multiple sclerosis (RRMS), but the exact mechanisms of protection from further brain pathology remain unclear. Here, Wang et al. used a combination of murine models and patient data to identify a role for B cell survival factor (BAFF) in conferring protection against gray matter pathology. In a model of experimental autoimmune encephalomyelitis (EAE) that results in gray matter damage, anti-BAFF treatment negated the effects of anti-CD20 treatment. In patients treated with anti-CD20, BAFF concentrations correlated with improved clinical outcomes. Together, these data support further investigation into a neuroprotective role of BAFF that emerges in the context of anti-CD20 B cell depletion. —Courtney Malo [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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