Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function  

Oleh:

Khatri, B. O. ; Man, S. ; Giovannoni, G.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Neurology (Official Journal of The American Academy of Neurology) vol. 72 no. 05 (Feb. 2009), page 402-409.
Topik: PERIPHERAL BLOOD MONONUCLEAR CELL (PMBC); MONOCLONAL ANTIBODIES (mAbs)

Ketersediaan

Perpustakaan FK Nomor Panggil: N11.K.2009.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Background: Accelerating the clearance of therapeutic monoclonal antibodies (mAbs) from the body may be useful to address uncommon but serious complications from treatment, such as progressive multifocal leukoencephalopathy (PML). Treatment of PML requires immune reconstitution. Plasma exchange (PLEX) may accelerate mAb clearance, restoring the function of inhibited proteins and increasing the number or function of leukocytes entering the CNS. We evaluated the efficacy of PLEX in accelerating natalizumab (a therapy for multiple sclerosis [MS] and Crohn disease) clearance and {alpha}4-integrin desaturation. Restoration of leukocyte transmigratory capacity was evaluated using an in vitro blood–brain barrier (ivBBB). Methods: Twelve patients with MS receiving natalizumab underwent three 1.5-volume PLEX sessions over 5 or 8 days. Natalizumab concentrations and {alpha}4-integrin saturation were assessed daily throughout PLEX and three times over the subsequent 2 weeks, comparing results with the same patients the previous month. Peripheral blood mononuclear cell (PBMC) migration (induced by the chemokine CCL2) across an ivBBB was assessed in a subset of six patients with and without PLEX. Results: Serum natalizumab concentrations were reduced by a mean of 92% from baseline to 1 week after three PLEX sessions (p < 0.001). Although average {alpha}4-integrin saturation was not reduced after PLEX, it was reduced to less than 50% when natalizumab concentrations were below 1 µg/mL. PBMC transmigratory capacity increased 2.2-fold after PLEX (p < 0.006). Conclusions: Plasma exchange (PLEX) accelerated clearance of natalizumab, and at natalizumab concentrations below 1 µg/mL, desaturation of {alpha}4-integrin was observed. Also, CCL2-induced leukocyte transmigration across an in vitro blood–brain barrier was increased after PLEX. Therefore, PLEX may be effective in restoring immune effector function in natalizumab-treated patients.

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