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BAFF 60-mer, and Differential BAFF 60-mer Dissociating Activities in Human Serum, Cord Blood and Cerebrospinal Fluid

Mahya EslamiEdgar MeinlHermann EibelLaure WillenOlivier DonzéOttmar DistlHolm SchneiderDaniel SpeiserDimitrios TsiantoulasÖzkan YalkınoğluEileen SamyPascal Schneider

出版	Universität, 2020
URL	http://books.google.com.hk/books?id=3eRJzgEACAAJ&hl=&source=gbs_api

註釋Abstract: B cell activation factor of the TNF family (BAFF/BLyS), an essential B cell survival factorof which circulating levels are elevated in several autoimmune disorders, is targeted inthe clinic for the treatment of systemic lupus erythematosus (SLE). The soluble formof BAFF can exist as 3-mer, or as 60-mer that results from the ordered assembly oftwenty 3-mers and that can be obtained from naturally cleaved membrane-bound BAFFor made as a recombinant protein. However, which forms of soluble BAFF exist andact in humans is unclear. In this study, BAFF 3-mer and 60-mer in biological fluidswere characterized for size, activity and response to specific stimulators or inhibitorsof BAFF. Human cerebrospinal fluids (CSF) from patients with multiple sclerosis andadult human sera contained exclusively BAFF 3-mer in these assays, also when BAFFconcentrations were moderately SLE or highly (BAFFR-deficient individual) increased.Human sera, but not CSF, contained a high molecular weight, saturable activity thatdissociated preformed recombinant BAFF 60-mer into 3-mer. This activity was lowerin cord blood. Cord blood displayed BAFF levels 10-fold higher than in adults andconsistently contained a fair proportion of active high molecular weight BAFF able todissociate into 3-mer but not endowed with all properties of recombinant BAFF 60-mer. If BAFF 60-mer is produced in humans, it is dissociated, or at least attenuated inthe circulation