Autoantibodies against protein antigens in Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy

Abstract

Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are representative inflammatory diseases affecting peripheral nerves. Recently autoantibodies against proteins located in nodes of Ranvier and paranodes, such as neurofascin (NF)186, moesin, NF155, contactin–1 (CNTN1) and contactin–associated protein 1 (caspr1), have been reported in a fraction of GBS and CIDP. Although clinical manifestations of CIDP are heterogeneous, CIDP with anti–NF155 or CNTN1 antibodies shows unique features. The common features include sensory ataxia, severe demyelination on nerve conduction study, very high cerebrospinal protein levels and poor response to intravenous immunoglobulin. Analysis of IgG subclasses of both antibodies has clarified predominant elevation of IgG4 subclass. Because IgG4 lacks complement binding and activating capabilities, IgG4 antibodies are regarded to directly interfere with the functions of the relevant antigens. Blocking the interaction between NF155 and CNTN1 results in detachment of terminal myelin loops from the axolemma, which is frequently recognized in longitudinal sections of sural nerves from patients with anti–NF155 or CNTN1 antibodies. Younger age at onset, higher frequency of tremor, hypertrophic nerve roots and strong association with HLA–DRB1*15, have been reported as characteristic features of anti–NF155 antibody–positive CIDP. By contrast, anti–CNTN1 antibody–positive CIDP patients present more advanced age of onset, higher frequency of concurrent nephrotic syndrome and an occasional acute to subacute onset with subsequent aggressive course. Because of rarity of patients with anti–NF186, moesin or caspr1 antibodies, clinical significance of these antibodies is not conclusive. This review summarizes autoantibodies against protein antigens in GBS and CIDP.