Surface Plasmon Resonance Sensing on Naturally Derived Membranes

A Remyelination-Promoting Human Antibody Binds Myelin with Extraordinary Affinity

Milan Vala, Luke R. Jordan, Arthur E. Warrington, L James Maher III, Moses Rodriguez, Nathan J. Wittenberg, Sang Hyun Oh

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAnalytical Chemistry
DOIs
StateAccepted/In press - Jan 1 2018

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Neurology
Surface plasmon resonance
Membranes
Autoantibodies
Antibodies
Animals
Antigens
Immunoglobulin M
Repair
Kinetics

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Surface Plasmon Resonance Sensing on Naturally Derived Membranes : A Remyelination-Promoting Human Antibody Binds Myelin with Extraordinary Affinity. / Vala, Milan; Jordan, Luke R.; Warrington, Arthur E.; Maher III, L James; Rodriguez, Moses; Wittenberg, Nathan J.; Oh, Sang Hyun.

In: Analytical Chemistry, 01.01.2018.

Research output: Contribution to journalArticle

Vala, Milan ; Jordan, Luke R. ; Warrington, Arthur E. ; Maher III, L James ; Rodriguez, Moses ; Wittenberg, Nathan J. ; Oh, Sang Hyun. / Surface Plasmon Resonance Sensing on Naturally Derived Membranes : A Remyelination-Promoting Human Antibody Binds Myelin with Extraordinary Affinity. In: Analytical Chemistry. 2018.
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