Invited Article: Human natural autoantibodies in the treatment of neurologic disease

Moses Rodriguez, Arthur E. Warrington, Larry R Pease

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Naturally occurring autoantibodies are molecules that are part of the normal immunoglobulin repertoire. This review focuses on three distinct groups of human monoclonal antibodies (mAb). These are human natural autoantibodies that, when injected into an animal model of human disease, stimulate remyelination in CNS demyelinating diseases, protect neurons and extend neuronal processes in CNS axonal disorders, and activate immune dendritic cells to produce cytotoxic T cells to clear metastatic tumors. Natural autoantibodies react to self antigens and are of relatively low affinity. They are derived from germline immunoglobulin genes and are usually polyreactive. Our experiments demonstrated CNS entry by autoradiography of labeled mAb and by MRI. Remyelinating mAb rHIgM22 clusters beta-integrin and mouse mAb O4 recognizes sulfatide. Neuronal outgrowth mAbs sHIgM42 and sHIgM12 appear to target carbohydrates on the surface of neurons. The mAb sHIgM12 (B7-DC-Xab) also is promising as therapeutic against metastatic tumors. It functions by binding and cross-linking the antigen B7-DC on dendritic cells, inducing tumor-specific cytotoxic T cells. All these mAbs activate a transient increase in intracellular calcium, signal via NFκb, and prevent apoptosis. The mAbs engage downstream signaling events that induce the primary function of the cell (that is, remyelination for oligodendrocytes, axonal preservation and neurite extension for neurons, or antigen presentation for dendritic cells). Natural human auto mAbs are a potentially important therapeutic technique in combating a wide spectrum of disease processes.

Original languageEnglish (US)
Pages (from-to)1269-1276
Number of pages8
JournalNeurology
Volume72
Issue number14
DOIs
StatePublished - Apr 7 2009

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Nervous System Diseases
Autoantibodies
Monoclonal Antibodies
Dendritic Cells
Neurons
Programmed Cell Death 1 Ligand 2 Protein
Integrin beta Chains
Sulfoglycosphingolipids
T-Lymphocytes
Animal Disease Models
Neoplasms
Immunoglobulin Genes
Central Nervous System Diseases
Immune System Diseases
Oligodendroglia
Autoantigens
Antigen Presentation
Demyelinating Diseases
Neurites
Autoradiography

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Invited Article : Human natural autoantibodies in the treatment of neurologic disease. / Rodriguez, Moses; Warrington, Arthur E.; Pease, Larry R.

In: Neurology, Vol. 72, No. 14, 07.04.2009, p. 1269-1276.

Research output: Contribution to journalArticle

Rodriguez, Moses ; Warrington, Arthur E. ; Pease, Larry R. / Invited Article : Human natural autoantibodies in the treatment of neurologic disease. In: Neurology. 2009 ; Vol. 72, No. 14. pp. 1269-1276.
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