About the Cover

Vol. 99 No. 2 (2023)

Human immunoglobulin G (IgG)-positive signals were greater in demyelinated regions, as shown with a dotted line in the cover image, whereas signals were weaker in healthy nerves and the perineurium. Lysolecithin is commonly used to establish animal models of demyelination. Direct local injection of lysolecithin into mouse sciatic nerves results in demyelination and inflammation at the injection site. Lysolecithin-induced demyelination transiently peaks at 7 days post-injection (dpi), followed by gradual remyelination and nerve recovery within approximately 3 weeks. This mouse model of demyelination was used to examine the effects of human intravenous immunoglobulin (IVIg) preparation on lesions in peripheral nerves. In this study (see the article in this issue, pp. 48–60), IVIg treatment was performed at 1 dpi of lysolecithin. Sciatic nerves were removed at 7 dpi and examined for the distribution of IVIg using cross-sections subjected to human IgG immunofluorescence staining. In IVIg-treated mice, the intensity of human IgG immunoreactions was greater in demyelinated regions, whereas reactions were weaker in healthy nerves and the perineurium.

Given its immunomodulatory and anti-inflammatory effects, high-dose IVIg therapy has become the first-line treatment for inflammatory demyelinating diseases. IVIg preparations produced by pharmaceutical companies represent a mixture of IgGs from several thousand healthy donors and are manufactured by purifying and processing human IgG. IVIg therapy is widely utilized in the treatment of inflammatory diseases, and its anti-inflammatory effects in patients with demyelinating conditions can be expected; however, the therapeutic mechanisms by which IVIg counteracts demyelination have not been completely elucidated. This study reports the following findings: (1) IVIg treatment promoted human IgG deposition in myelin debris found in demyelinated lesions and prevented the exacerbation of lysolecithin-induced demyelination in mouse sciatic nerves; (2) IVIg preparations were comprised anti-L-MPZ antibodies; and (3) human IgG in IVIg was deposited in myelin debris, possibly through L-MPZ and may modify the demyelination process. Thus, anti-L-MPZ antibodies can be a potential novel candidate for IVIg therapy for peripheral demyelination.

Masahiro Kaneko
Associate Professor, Laboratory of Immunology, Yokohama University of Pharmacy