Novel pathomechanisms in inflammatory neuropathies

Abstract

Inflammatory neuropathies are rare autoimmune-mediated disorders affecting the peripheral nervous system. Considerable progress has recently been made in understanding pathomechanisms of these disorders which will be essential for developing novel diagnostic and therapeutic strategies in the future. Here, we summarize our current understanding of antigenic targets and the relevance of new immunological concepts for inflammatory neuropathies. In addition, we provide an overview of available animal models of acute and chronic variants and how new diagnostic tools such as magnetic resonance imaging and novel therapeutic candidates will benefit patients with inflammatory neuropathies in the future. This review thus illustrates the gap between pre-clinical and clinical findings and aims to outline future directions of development.

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis

“…Both MC-induced EAN and GBS exhibit an acute onset with monophasic course of disease. In addition, both in MC-induced EAN and in certain forms of GBS, a predominant infiltration of the PNS from macrophages and T cells is observed (Schafflick et al, 2017, Soliven, 2014Zhang et al, 2012). The contribution of T cells and macrophages to EAN is also proven by the ability of P2-specific T cell lines to transfer EAN to healthy animals (Soliven, 2014) and the possibility to prevent EAN by depletion of macrophages by administration of silica dust or by blocking macrophage function with cyclooxygenase inhibitors (Soliven, 2014).…”

“…Guillain-Barré syndrome (GBS) is a heterogeneous disorder of the peripheral nervous system (PNS), representing at least five different entities, including forms with predominant motor component, such as AIDP, AMSAN, and AMAN, and other variants, such as Fisher syndrome and acute pan-autonomic neuropathy. Most forms of GBS are characterized by immune-mediated demyelination and axonal damage of peripheral nerves that is clinically associated to progressive weakness of the limbs (Schafflick et al, 2017;Soliven, 2014).…”

“…Experimental autoimmune neuritis (EAN) is a known and validated model of demyelination of the PNS, that can be induced in susceptible strains of rodents by immunization with myelin proteins P0, P2 and PMP22 (Schafflick et al, 2017). Clinical, histological and immune-pathogenic similarities between EAN and human GBS have made the myelin component (MC)-induced EAN a suitable and validated model of GBS.…”

“…The contribution of T cells and macrophages to EAN is also proven by the ability of P2-specific T cell lines to transfer EAN to healthy animals (Soliven, 2014) and the possibility to prevent EAN by depletion of macrophages by administration of silica dust or by blocking macrophage function with cyclooxygenase inhibitors (Soliven, 2014). Like in human GBS, MC-induced EAN is associated to dysregulated production of Th1/Th17 cytokines and impaired function and numbers of regulatory T cells, along with upregulated expression of Toll like receptors during the course of the diseases (Jung et al, 2004;Schafflick et al, 2017).…”

“…Nonetheless, like with most models of human autoimmune diseases, caveats should be kept in mind when the rodent EAN model is used as model of GBS, as this model fails to fully mirror the heterogenic complexity of the human disease counterpart. For example, auto-reactivity against myelin proteins has only been observed in a small proportion of GBS patients and the infiltration of mononuclear cells and immune cellmediated myelin destruction in the PNS is known to occur only in a proportion of GBS patients who exhibit demyelinating disease phenotype (Schafflick et al, 2017).…”