Autoimmunity to Neuronal Proteins in Neurological Disorders pp. 49-87
Authors: (Ruth Huizinga, Sandra Amor, Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands)
Abstract: Autoreactive T-cell responses directed to myelin proteins in the central nervous system (CNS) are widely believed to be fundamental in the pathology of multiple sclerosis (MS). This view has dominated the research field in MS for many years and led to the reliance on experimental models of neurological disease following immunisation with myelin antigens. Such experimental diseases have developed as the central paradigm to investigate underlying mechanisms operating in MS as well as the preclinical development of therapeutic strategies. This long-standing concept has recently shifted and evidence is rapidly accumulating indicting a significance role of axonal damage and neurodegeneration in disease. Indeed axonal damage is now considered to be the major cause of irreversible neurological disability in MS patients. One correlate of axonal damage in MS is the presence of antibodies against neurofilament light protein, a major component of the axonal cytoskeleton. Contrary to extensive literature on pathogenic myelin autoimmunity the possible pathogenic role of autoimmunity to axonal antigens in MS has so far been ignored. Our recent experimental data indicate that autoimmunity to axonal antigens, as described in MS, is pathogenic rather than acting merely as a surrogate marker for axonal degeneration.