Reduced level of sialylated IgG antibody in the CSF of patients with multiple sclerosis

OBJECTIVE: To determine IgG antibody sialylation in the CSF and paired serum of patients with multiple sclerosis. BACKGROUND: A characteristic feature of the CNS inflammatory response in multiple sclerosis (MS) is the intrathecal synthesis of IgG and the presence of oligoclonal bands (OCBs). IgG form immune complexes with the antigen, and generate negative feedback regulation through crosslinking the B cell receptor with IgG inhibitory receptor FcγRIIB, which inhibits BCR signaling and thereby B cell activation and IgG antibody (Ab) production. Recent studies showed that asialylated IgG are proinflammatory and induced by the combination of T cell-dependent protein antigens and proinflammatory costimulation. DESIGN/METHODS: We purified IgG Ab in CSF and paired serum from 12 MS patients and 9 inflammatory CNS controls with Protein A Magnetic Beads. The purified IgG were quantified for sialic acid levels using immunoblots probed with biotinylated lectin Sambucus nigra agglutinin (SNA) specific for sialic acid, followed by detection with HRP-conjugated NeutrAvidin. Biotinylated anti-human IgG blots were used as background control. RESULTS: We found that there was a significant decrease of sialylated IgG Fc in the CSF compared to paired serum ( p =6.2 -8 ). In contrast, no significant difference of IgG Fc sialylation was detected in the CSF and serum of inflammatory controls ( p =0.18) with other neurological diseases. CONCLUSIONS : The discovery that significantly lower levels of IgG sialyaltion in MS CSF opens up new possibilities to design better immunomodulatory antibodies for MS and other demyelinating diseases. Disclosure: Dr. Yu has nothing to disclose. Dr. Dennison has nothing to disclose. Dr. Pointon has nothing to disclose. Dr. Vollmer has received personal compensation for activities with Cleveland Clinic, Novartis, Mandell Center for Multiple Sclerosis, Teva Neuroscience, Questcor Pharmaceuticals, Biogen Idec, Xenoport, University of Florida PeerView, and Krog & Partners. Dr. Vollmer has received research support from Biogen Idec, Teva Neuroscience, Genzyme Corp., Ono Pharmaceuticals, Elan Pharmaceuticals, Novartis, Avanir Pharmaceuticals, and Janssen Pharmaceutica.