Mechanisms of autoimmunity in the central nervous system: Disturbance of natural autoimmunity, infectious agents, cell contribution and antibody signatures

Abstract

Autoimmunity in the central nervous system (CNS) seems to be a physiological process that might normally occur from the very early stages of fetal development. There is some evidence suggesting that CNS autoimmunity could participate in brain structuring, early antigen recognition and immune tolerance. Interestingly, clues to the occurrence of such early events can be discovered in cord blood samples from newborns and peripheral blood, as well as cerebrospinal fluid samples from adults by means of antibody profiling, through antigen microarray technology. In the past, results from those studies raised the possibility for the existence of a physiological autoantibody network recognizing self-key antigens, as proposed by Irun Cohen many years ago. After examining those findings, I suggest the existence of a specific autoantibody network recognizing resident antigens, which would eventually behave as a two-sided sword in the CNS. It might act as a framework for the organization of local immune homeostasis, which is necessary for the maintenance of neurophysiological processes. On the contrary, it might also participate in the pathogenesis of abnormal autoimmunity after the loss of tolerance to resident antigens. The disturbance of this synchronic homeostasis by environmental stimuli might trigger abnormal reactivity, influenced by favorable genetic conditions. In this regard, the evidence supporting some cutting-edge concepts that are intended to comprehensively characterize the molecular and cellular mechanisms likely implicated in abnormal CNS autoimmunity (primarily in multiple sclerosis) is presented. Finally, the usefulness of the detection of specific disease-associated autoantibodies and autoantibody profiling as clinical tools is also approached.