Breakdown of blood‐nerve barrier in immune‐mediated neuropathy

Abstract

AbstractThe blood–nerve barrier (BNB) is a peripheral nerve‐specific capillary barrier system that blocks the entrance of pathogenic leukocytes and toxic soluble mediators, such as cytokines, chemokines and immunoglobulin, from the circulating blood to the parenchyma of the peripheral nervous system (PNS). The pathological breakdown of the BNB might play pivotal pathophysiological roles in the onset of various immune‐mediated neuropathies, including Guillain–Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and a subset of diabetic neuropathy. However, fewer studies have so far been carried out regarding the cell biology and clinical significance of the BNB compared with the total number of studies of the blood–brain barrier because of the lack of adequate human cell lines derived from the BNB. In recent studies, we successfully established human immortalized cell lines of BNB origin in our laboratory and describe their detailed cellular properties. Although CIDP is now recognized as involving several clinical phenotypes, including both typical CIDP and atypical CIDP, disruption of the BNB could determine the clinical phenotype, severity and course of disease in the case of CIDP. Although the underlying pathomechanisms of MMN have not yet been clarified, BNB breakdown can cause persistent demyelination at sites of conduction block in patients with MMN. In the present review article, we highlight the recently acquired insight regarding the pathology and pathophysiology of BNB breakdown in the setting of the immune‐mediated neuropathy. In addition, we discuss how this knowledge can be used to develop novel therapeutic strategies for treating immune‐mediated neuropathies by manipulating the BNB.