Serum CXCL13 reflects local B-cell mediated inflammatory demyelinating peripheral neuropathy

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.

Serum, but Not Saliva, CXCL13 Levels Associate With Infiltrating CXCL13+ Cells in the Minor Salivary Gland Lesions and Other Histologic Parameters in Patients With Sjögren’s Syndrome

“…However, the correlation of CXCL13 serum levels with the number of CXCL13-positive cells within the MSG inflammatory lesions found in this study and with various histologic parameters, including the degree of MSG inflammation and the presence of eGCs, shown in this and previous studies (24,26,29), suggest that at least a part of the elevated CXCL13 serum levels in pSS patients arise from the affected salivary glands. This is in agreement with previous findings linking local and systemic autoimmune responses in pSS (33,52,53), as well as relevant findings in other autoimmune diseases suggesting that CXCL13 serum levels reflect the local inflammation in the affected organs (18,54). On the other hand, we have previously observed that the number of infiltrating FDCs in MSG lesions of pSS patients decreases in more severe lesions (33).…”

CXCL13/CXCR5 signalling is pivotal to preserve motor neurons in amyotrophic lateral sclerosis

“…Measuring CXCL13 concentration in the CSF could be a clinical adjunct to discriminate ALS from other neurological diseases. This because, unlike ALS, CXCL13 dramatically increased in the CSF of patients with other inflammatory diseases such as encephalitis [66], chronic inflammatory demyelinating polyneuropathy [67], MS [26,68], LMN [51] or rheumatoid meningitis [69].…”

Adaptive autophagy reprogramming in Schwann cells during peripheral demyelination

“…SC transdifferentiation to DSCs has been recently suggested to be involved in inflammatory demyelinating neuropathies [ 33 ]. We thus examined whether a similar alteration in autophagy is induced during demyelination in EAN, a rat model of inflammatory demyelinating neuropathy [ 18 ]. The levels of p62 were found to be increased in the SCs of EAN rats compared to those of control rats (Fig.…”

“…Female rats aged 7–12 weeks and weighing 160–200 g were used. Active EAN was induced in the rats as described previously [ 18 ]. Briefly, each rat was injected in both hind footpads with an emulsion containing 100 mg SP-26, a neuritogenic peptide homologous to amino acids 53–78 of bovine myelin P2 protein (Shimadzu), and Freund’s complete adjuvant (Sigma-Aldrich, F5881; M. tuberculosis H37Ra, 5 mg/mL).…”