Antibodies in Autoimmune Human Neurological Disease: Pathogenesis and Immunopathology

Abstract

Immune-mediated processes represent a rapidly expanding categorical etiology for neurological disease manifestations spanning all subspecialties of neurology. Neural autoantibodies can be grossly divided into two main groups based on localization of the antigen: intracellular and cell membrane/synaptic antibodies. Antibodies reactive with neuronal membrane antigens have been identified in serum and cerebrospinal fluid of patients developing neurological disease either independent of or associated with cancer comorbidity, whereas antibodies directed against intracellular targets have a much higher rate of associated malignancy. Antibodies to neuronal membrane proteins such as the N-methyl-D-aspartate (NMDA) receptor are considered directly pathogenic based on disease models. Similar evidence exists for far fewer autoantibodies directed against intracellular targets. Attempts to produce an antibody-mediated animal model of human paraneoplastic disease have been unsuccessful to date. In this article, we review antineural antibodies and their clinical associations, briefly discuss recently characterized entities, and present proposed mechanisms of antibody pathogenicity.

Glial Cells as Regulators of Neuroimmune Interactions in the Central Nervous System

“…Multiple sclerosis (MS) has been the most commonly considered human disorder within the latter category. There is now, however, increasing recognition of specific Ab-linked disorders, including anti-aquaporin 4 Ab-associated neuromyelitis optica, myelin oligodendrocyte glycoprotein (MOG) Ab-mediated demyelinating disease, and NMDA-receptordirected autoimmune encephalomyelitis (6)(7)(8). This Pillars of Immunology commentary will describe progress made in our understanding of the contribution of resident cells in the CNS to these dynamic processes.…”

Autoantibodies to synapsin I sequestrate synapsin I and alter synaptic function

“…A large battery of autoantibodies directed to neuronal proteins have been discovered in sera and CSF of patients suffering from a variety of neurological diseases 1 . These autoantibodies target two main classes of antigens, namely cell surface and intracellular antigens.…”

New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis

“…In such a paraneoplastic setting, the ectopic GFAPα expression is considered to trigger an autoimmune response against the physiological astrocytic protein in the CNS. In contrast to antigens that are expressed on the extracellular surface of the target cell and are directly accessible by autoantibodies, GFAPα is an intracellular antigen and the autoantibodies are most likely non-pathogenic but the disease is triggered and propagated by a T cell-mediated immune response [ 17 , 46 ]. In idiopathic patients the trigger for GFAP autoimmunity remains elusive.…”