Brain-Targeted Autoimmunity: Beyond Multiple Sclerosis

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Background

Brain-targeted autoimmunity has been extensively studied in the context of pathologies that undoubtedly involve dysfunctions of the adaptive immune system. These conditions notably include multiple sclerosis (MS), neuropsychiatric manifestations of systemic lupus erythematous (SLE) and paraneoplastic neurological syndromes. However, there is now increasing investigation into the role of autoimmune-related mechanisms in the pathogenesis of neurological or psychiatric conditions that were previously considered to be either (i) non immune-mediated or (ii) involving innate immunity only. Indeed, in the past decade, brain-directed autoimmunity has been either demonstrated or proposed to possibly contribute or impact the pathophysiology of at least 4 groups of central nervous system (CNS) disorders:

1) Neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD).
2) Psychiatric diseases including autism spectrum disorders (ASD), schizophrenia, bipolar disorder and obsessive compulsive disorder.
3) Post-lesional conditions following stroke, brain injury or spinal cord injury.
4) Rare CNS disorders such as narcolepsy, some forms of epilepsy, Susac’s syndrome, Rasmussen’s encephalitis, stiff-man syndrome and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS).

Unexpectedly, brain-targeted autoimmunity has also been demonstrated under physiological conditions and has been shown to both shape behavior and cognition and to support brain homeostasis. This groundbreaking finding is of crucial importance as it raises the question whether physiological and pathological brain-directed autoimmunity may be linked. Whether pathological brain-directed autoimmunity develops de novo, or as a distortion of physiological autoimmunity, remains poorly understood. Furthermore, while to some extent a common pathophysiological process targeting neurons is present in most of the above-mentioned groups of disorders, it is unknown whether similarities in brain-targeted autoimmune responses are also exhibited between these disorders. These studies raise the question of whether a common grounding base involved in the development of pathological (or protective) autoimmunity underlies such conditions? Similarly, synaptic antigens appear to be the main auto-antigens targeted in CNS conditions that are essentially characterized by neuronal dysfunctions rather than neuronal cell loss, which mostly comprise psychiatric disorders. Finally, although this point has not been formally demonstrated, it may be anticipated that in post-lesional conditions following stroke, brain injury or spinal cord injury, self-antigens related to the growth and/or guidance of axons could be specifically targeted.

This Research Topic aims to provide a synthetic view of brain-targeted autoimmunity beyond MS, in order to help identify shared vs. disease-specific autoimmune-related mechanisms and to pave the way for future therapeutic immune interventions in a broad range of CNS disorders. We welcome the submission of Original Research, Review and Mini-Review articles based on human and/or animal studies involving molecular, cellular and/or systems biology approaches that cover the following sub-topics:

1. The role of autoimmunity in neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, ALS and FTD.
2. The involvement of autoimmunity in the pathogenesis of psychiatric disorders such as autism spectrum disorders, schizophrenia, bipolar disorder and obsessive compulsive disorder.
3. The role of autoimmunity in post-lesional conditions folowing stroke, brain injury and spinal cord injury.
4. The role of autoimmunity in rare CNS diseases such as narcolepsy, some forms of epilepsy, Susac’s syndrome, Rasmussen’s encephalitis, stiff-man syndrome and PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus).
5. The impact of physiological autoimmunity on behavior and cognition.

Keywords: Autoimmunity, Multiple Sclerosis, CNS, Neurodegeneration, Neurodegenerative diseases

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