TY - JOUR
T1 - Surface Plasmon Resonance Sensing on Naturally Derived Membranes
T2 - A Remyelination-Promoting Human Antibody Binds Myelin with Extraordinary Affinity
AU - Vala, Milan
AU - Jordan, Luke R.
AU - Warrington, Arthur E.
AU - Maher, L. James
AU - Rodriguez, Moses
AU - Wittenberg, Nathan J.
AU - Oh, Sang Hyun
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/11/6
Y1 - 2018/11/6
N2 - RHIgM22 is a recombinant human monoclonal IgM designed to promote remyelination, and it is currently in Phase I clinical trials in patients with multiple sclerosis (MS). In animal models of demyelination, a single low dose of rHIgM22 stimulates oligodendrocyte maturation, induces remyelination, preserves axons, and slows the decline of locomotor deficits. Natural autoantibodies like rHIgM22 typically bind to multiple antigens with weak affinity. rHIgM22 binds to oligodendrocytes and myelin. Because the antigens for rHIgM22 is prevalent within and exclusive to central nervous system (CNS) myelin, we used CNS myelin particles in combination with surface plasmon resonance to determine the kinetic and affinity constants for the interaction of rHIgM22 to myelin. We found that both the serum and recombinant forms of the antibody bind to myelin with very small dissociation constants in the 100 pM range, which is highly unusual for natural autoantibodies. The extraordinary affinity between rHIgM22 and myelin may explain why such a low effective dose can stimulate CNS repair in animal models of demyelination and underlie the accumulation of rHIgM22 in the CSF in treated MS patients by targeting myelin.
AB - RHIgM22 is a recombinant human monoclonal IgM designed to promote remyelination, and it is currently in Phase I clinical trials in patients with multiple sclerosis (MS). In animal models of demyelination, a single low dose of rHIgM22 stimulates oligodendrocyte maturation, induces remyelination, preserves axons, and slows the decline of locomotor deficits. Natural autoantibodies like rHIgM22 typically bind to multiple antigens with weak affinity. rHIgM22 binds to oligodendrocytes and myelin. Because the antigens for rHIgM22 is prevalent within and exclusive to central nervous system (CNS) myelin, we used CNS myelin particles in combination with surface plasmon resonance to determine the kinetic and affinity constants for the interaction of rHIgM22 to myelin. We found that both the serum and recombinant forms of the antibody bind to myelin with very small dissociation constants in the 100 pM range, which is highly unusual for natural autoantibodies. The extraordinary affinity between rHIgM22 and myelin may explain why such a low effective dose can stimulate CNS repair in animal models of demyelination and underlie the accumulation of rHIgM22 in the CSF in treated MS patients by targeting myelin.
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U2 - 10.1021/acs.analchem.8b02664
DO - 10.1021/acs.analchem.8b02664
M3 - Article
C2 - 30231202
AN - SCOPUS:85055092671
SN - 0003-2700
VL - 90
SP - 12567
EP - 12573
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 21
ER -