Antibodies as Mediators of Brain Pathology

Abstract

The brain is normally sequestered from antibody exposure by the blood brain barrier. However, antibodies can access the brain during fetal development before the barrier achieves full integrity, and in disease states when barrier integrity is compromised. Recent studies suggest that antibodies contribute to brain pathology associated with autoimmune diseases such as systemic lupus erythematosus and neuromyelitis optica, and can lead to transient or permanent behavioral or cognitive abnormalities. We review these findings here and examine the circumstances associated with antibody entry into the brain, the routes of access and the mechanisms that then effect pathology. Understanding these processes and the nature and specificity of neuronal autoantibodies may reveal therapeutic strategies toward alleviating or preventing the neurological pathologies and behavioral abnormalities associated with autoimmune disease.

Molecular and Functional Neuroscience in Immunity

“…Autoimmune diseases, including systemic lupus erythematosus, have an impact on brain function and are associated with neurological complications, including cognitive deterioration and fatigue (186, 187). Peripheral antibodies, released during the disease and targeting the brain glutamatergic system, have been directly implicated in brain derangements (188–191).…”

“…An interesting approach is antibody neutralization by using a decoy antigen to prevent antibody interactions with target tissues (192). A related question is whether cytokine-based or antibody-based therapies can be used in neuroprotective strategies (193) or for improving brain function (187). As recently suggested, antibodies with a role in brain pathology in autoimmune conditions could potentially have beneficial effects in individuals with underlying brain glutamatergic or dopaminergic hypofunction (187).…”

The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System

“…In addition to the importance of ENS on GI homeostasis, ENS also serves as a relay station along the MGB axis that conveys information from the luminal microenvironment to the CNS. The mechanisms underlying MGB axis communication involve the immune and endocrine system, neural pathways via the vagus nerve, and the microbiota-dependent modulation of CNS 8, 89, 90, 91, 92, 93, 94, 95. For instance, SCFAs produced by microbiota ensure the integrity of the blood-brain barrier by up-regulating tight junction proteins, 42 and regulate the maturation and activation of microglial cells 41 .…”

A comprehensive review of the neonatal Fc receptor and its application in drug delivery

“…such as systemic lupus erythematosus, neuromyelitis optica (Brimberg et al, 2015), myasthenia gravis (Tamburrini et al, 2015), type 1 diabetes (Leslie et al, 2015) and hepatitis (Sener, 2015), among many others.…”