The possible role of peripherally generated cross-reactive IgG in breakdown of the blood–brain barrier and initiation of multiple sclerosis

The initiating event in multiple sclerosis (MS) pathogenesis is not known yet. However, in general, breakdown of the blood-brain barrier (BBB) and subsequent infiltration of immune cells into the central nervous system (CNS) has been thought to be the main initiating event. Nonetheless, the mechanism by which the BBB gets disrupted and allows immune cells to infiltrate into the CNS is not fully understood. Evidence indicates that prior to cellular infiltration, over passing peripherally generated cross-reactive immunoglobulin G (IgG) through the transiently permeable BBB during systemic inflammation, hypoxia, hyperthermia, transient hypertension or acute stresses may cause CNS inflammation, BBB breakdown and then initiation of MS disease. Here, we discuss the possible detailed mechanisms that may be involved in cross-reactive IgG-mediated MS autoimmunity.