• Haruki Koike, Ryoji Nishi, Shohei Ikeda, Yuichi Kawagashira, Masahiro Iijima, Masahisa Katsuno, and Gen Sobue.
• From the Department of Neurology (H.K., R.N., S.I., Y.K., M.I., M.K., G.S.) and Research Division of Dementia and Neurodegenerative Disease (G.S.), Nagoya University Graduate School of Medicine, Japan. koike-haruki@med.nagoya-u.ac.jp sobueg@med.nagoya-u.ac.jp.
• Neurology. 2018 Dec 4; 91 (23): 1051-1060.

AbstractChronic inflammatory demyelinating polyneuropathy (CIDP) is a form of chronic neuropathy that is presumably caused by heterogeneous immune-mediated processes. Recent advances in the search for autoantibodies against components expressed at nodal regions, such as the nodes of Ranvier and paranodes, have substantially contributed to clarifying the pathogenesis of CIDP in a subpopulation of patients. In particular, immunoglobulin G4 (IgG4) antibodies to paranodal junction proteins, including neurofascin-155 and contactin-1, have attracted the attention of researchers. Paranodal dissection resulting from the attachment of IgG4 at paranodal junctions and the absence of macrophage-induced demyelination are characteristic pathologic features in patients who have these antibodies. By contrast, the mechanisms of neuropathy in cases with classical macrophage-induced demyelination remain unclear despite the long-standing recognition of this process in CIDP. In addition to complement-dependent damage provoked by autoantibodies, recent studies have shed light on antibody-dependent phagocytosis by macrophages without participation of complements. However, a direct association between specific autoantibodies and macrophage-induced demyelination has not been reported. Electron microscopic examination of longitudinal sections of sural nerve biopsy specimens suggested that macrophages recognize specific sites of myelinated fibers as the initial target of demyelination. The site that macrophages select to initiate myelin breakdown is located around the nodal regions in some patients and internode in others. Hence, it seems that the components that distinguish between the nodal regions and internode play a pivotal role in the behavior of macrophages that initiate phagocytosis of myelin. Further studies are needed to elucidate the mechanisms underlying macrophage-induced demyelination from this perspective.© 2018 American Academy of Neurology.

11 keywords...

hide…