Abstract
Immune damages on the peripheral myelin sheath under pro-inflammatory milieu result in primary demyelination in inflammatory demyelinating neuropathy. Inflammatory cytokines implicating in the pathogenesis of inflammatory demyelinating neuropathy have been used for the development of potential biomarkers for the diagnosis of the diseases. In this study, we have found that macrophages, which induce demyelination, expressed a B-cell-recruiting factor CXC chemokine ligand 13 (CXCL13) in mouse and human inflammatory demyelinating nerves. The serum levels of CXCL13 were also higher in inflammatory demyelinating neuropathic patients but not in acute motor axonal neuropathy or a hereditary demyelinating neuropathy, Charcot-Marie-Tooth disease type 1a. In addition, CXCL13-expressing macrophages were not observed in the sciatic nerves after axonal injury, which causes the activation of innate immunity and Wallerian demyelination. Our findings indicate that the detection of serum CXCL13 will be useful to specifically recognize inflammatory demyelinating neuropathies in human.
Highlights
Inflammatory peripheral neuropathy encompasses various types of peripheral neuropathies associated with nerve inflammation, including Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)[1]
To identify pro-inflammatory condition-specific cytokines expressed in demyelinating Schwann cell (SC), we compared cytokine expression profiles in the neuropathic sciatic nerves of B7-2 knockout Non-obese diabetic (NOD) (B7-2KO) mice, that show a spontaneous autoimmune demyelinating neuropathy[8,16] and injured C57BL/6 nerves with a commercial cytokine expression panel[17]
The expression levels of intercellular adhesion molecule-1 (ICAM-1), interleukin-1 receptor antagonist, tissue inhibitor of metalloproteinases 1, C-C chemokine ligand 2 (CCL2), and IL-16 were increased in the sciatic nerves of both B7-2KO mice and injured C57BL/6 mice compared to each control of both conditions (Fig. 1A,B)
Summary
Inflammatory peripheral neuropathy encompasses various types of peripheral neuropathies associated with nerve inflammation, including Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)[1]. GBS includes acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and Miller Fisher syndrome based on clinical and electrophysiological findings. The discovery of anti-ganglioside antibodies has provided diagnostic, and mechanistic insights into the development of AMAN4. Multiple secretory molecules, including inflammatory cytokines, are expressed by immune cells and dedifferentiated SCs6–11, and these proteins may be potential targets for biomarker development. The inflammatory demyelination-specific expression of CXCL13 in the mouse and human peripheral nerves was represented in the sera of inflammatory demyelinating neuropathy patients, but not in the sera of AMAN and CMT1a patients, indicating the potential diagnostic utility of CXCL13 in inflammatory demyelinating peripheral neuropathy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
