Recent advances in the neuroimmunology of cell-surface CNS autoantibody syndromes, Alzheimer’s disease, traumatic brain injury and schizophrenia

Abstract

In this update, we review recent advances in antibody-associated disorders of the central nervous system, and the immune mechanisms which may contribute to Alzheimer's disease, traumatic brain injury and schizophrenia. The field of neuroimmunology is rapidly developing and has concerned itself with an expanding portfolio of diseases. The core neuroimmunological diseases remain, multiple sclerosis, neuromyelitis optica, primary inflammatory and antibody-associated disorders of the central and peripheral nervous system (including Myasthenia Gravis and other disorders of neuromuscular junction and muscle, paraneoplastic syndromes, paraproteinaemic neuropathies), and the neurological involvement seen in systemic inflammatory diseases including lupus, sarcoidosis and vasculitis. But it is increasingly realised that immune mechanisms may contribute to the pathogenesis of degenerative diseases including Alzheimer's disease, traumatic brain disease and psychiatric diseases including schizophrenia and depression. These common and devastating disorders, often without effective disease-modifying therapies, are yet to be seen in a conventional neuroimmunology clinic, but the immune mechanisms identified have encouraged research into novel therapeutic approaches for them.

Overview of Traumatic Brain Injury: An Immunological Context

“…The unique compositions of these inflammasomes depend on the extent and type of cell and tissue damage. Some reports suggested the specific contributions of NLR family proteins (NLRP3-inflammasome) after TBI [ 110 , 111 ]. The NLRP3-inflammasome has been detected in neurons, astrocytes and microglia in the cortex after TBI [ 110 ], and the NLRP3-inflammasome complex is associated with increases in the aforementioned IL1-β and IL18 [ 108 , 110 , 112 ].…”

Utility of Autoantibodies as Biomarkers for Diagnosis and Staging of Neurodegenerative Diseases

“…Furthermore, these conditions have been found to exist with varying phenomenological descriptions based on autoantibody profiles. In fact, after its discovery, anti-NMDAR encephalitis was named after its reported cause, NMDAR autoantibodies (Kayser & Dalmau, 2014;Needham & Zandi, 2014). Considering that different autoantibodies can be found giving rise to seemingly similar psychiatric conditions, this discovery provides insight into disease prognosis and treatment based on the autoantibody profiles present.…”

“…Alzheimer's disease (AD), a CNS proteinopathy discussed in Section 4.6, is gaining popularity in the guise of a neuroinflammatory-mediated condition (Needham & Zandi, 2014). Here, the presence of autoantibodies is now given much attention in basic science and translational research attempts for presymptomatic diagnostics and treatment regimens (Terryberry et al, 1998).…”

Schizophrenia in 2020: Trends in diagnosis and therapy

“…Recent genome‐wide association studies converge on genes involved in the regulation of synaptic activities, neurodevelopment and immune functions . An interesting new aspect here is the finding of immunity‐related genes, which seems to vindicate theories about an involvement of neuroimmunologic processes in the pathogenesis of schizophrenia . Also, there is now a subtype of patients with symptoms of schizophrenia, who have autoantibodies against the N‐methyl‐D‐aspartate receptor, and whose psychotic symptoms respond to immunologic therapies .…”