Clinical and pathophysiological implications of autoantibodies in autoimmune neuropathies

Autoimmune neuropathies (AN) constitute a heterogeneous group of rare and disabling diseases where the immune system targets peripheral nervous system (PNS) antigens, resulting in progressive motor weakness and sensory loss [1], [2] (Table 1). According to their clinical course, AN can be divided into acute and chronic. Acute disorders include Guillain-Barré syndrome (GBS), which is divided into several subtypes including acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and the Miller-Fisher syndrome (MFS), among other variants [3], [4], [5]. The chronic-onset group includes chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and polyneuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (IgM-MGUSP) [2], [6]. This group of disorders has traditionally been referred to as inflammatory neuropathies, but the absence of overt inflammation in some of the diseases of the group is making the field shift to a broader term that includes all autoimmune neuropathies. Classically, the disorders that are not pure autoimmune neuropathies (because they either associate with systemic diseases or with neoplasms), are usually excluded from this group because they have different clinical and pathophysiological features. The recent changes in the field with the appearance of novel pure autoimmune neuropathies that are not inflammatory, such as autoimmune nodopathies, suggest that a novel taxonomy may be needed to understand and study these disorders better.

Early identification and treatment of these disorders is important because they respond to immunosuppressant or immunomodulatory drugs [1], [2], [6], [7], [8]. These diseases are diagnosed according to clinical and electrophysiological criteria that are broad enough to include all patients that may benefit from immune therapies. This results in the inclusion, within the same diagnostic categories (GBS, CIDP…), of heterogeneous diseases that have different underlying pathogenic mechanisms and may respond differently to specific therapies [2]. Moreover, diagnosis is often delayed due to diverse reasons, including the lack of disease biomarkers [9].

Although the pathophysiology is only partially known, humoral factors and, among them, autoantibodies, play a role in AN pathogenesis. Autoantibodies targeting gangliosides in acute and chronic forms of AN have long been known and are associated with specific AN subtypes [10]. More recently, autoantibodies targeting the node of Ranvier (NR) have been described in autoimmune nodopathies, a subset of rare AN presenting with specific clinical features that have boosted research in the field and further support the use of autoantibodies as disease-classifying biomarkers [2], [7], [8], [11], [12], [13], [14].

In this paper, we will review the clinical and pathophysiological features of autoantibodies in AN. Discussion of autoantibody-associated nerve disorders appearing in the context of systemic inflammatory or paraneoplastic disorders is beyond the scope of this review.

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