Recombinant immune complexes (rICs) as a therapeutic for Multiple Sclerosis (MS): effect on myeloid cell activation

Abstract Monocyte recruitment into the central nervous system (CNS) is critical for driving pathology in neuroinflammatory diseases such as MS. The monocytic influx well activation of resident myeloid cells contribute to and subsequent re-activation autoreactive T cells, ultimately leading demyelinating lesions, axonal damage, progressive paralysis. Using murine model MS, experimental autoimmune encephalitis (EAE) we tested a rIC, M019, determine its efficacy reducing cell subsequently disease severity. Four days following induction EAE with MOG peptide, daily treatment M019 inhibited clinical symptoms including weight loss demyelination dose-dependent manner. also delayed or prevented SJL relapsing remitting demonstrating effectiveness against several forms EAE. Analysis immune infiltrate spinal cords vehicle treated mice revealed that significantly inhibits infiltration lymphoid CNS. were present CNS had reduced levels MHC II suggesting they are inefficient at antigen presentation cells. Microglia did not upregulate expression compared their activation. binds directly monocytes periphery via CD16 (FcγRIII) CD32 (FcγRII) detected increased chemokines sera mice. These results suggest blocks migration CNS, potentially phenotypic functional changes monocytes.