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

Graphical abstract The initiating event in multiple sclerosis (MS) pathogenesis has not known yet. However, in general, break down of blood–brain barrier (BBB) and subsequently infiltration of immune cells into central nervous system (CNS) has thought to be the main initiating event. There are evidences indicate that prior to cellular infiltration, over passing of peripherally generated cross-reactive IgG through the transiently permeable BBB during systemic inflammation, transient hypertension, hypoxia, hyperthermia, or acute stresses may cause to CNS inflammation, BBB break down and then initiation of MS disease.