抗neurofascin 155抗体，抗contactin–1抗体陽性ノドパチー

抄録

It has been recognized that autoantibodies against paranodal cell adhesion proteins, such as neurofascin 155 (NF155) and contactin–1 (CNTN1), are detected in a small subset of patients fulfilling criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IgG subclass analysis of these antibodies reveals the predominant elevation of the IgG4 subclass. Patients with IgG4 autoantibodies against NF155 or CNTN1 have some distinct clinical features, including poor response to intravenous immunoglobulin and high efficacy of rituximab, leading to the separation of this group from CIDP as autoimmune nodopathy in the revised international guideline on diagnosis and treatment of CIDP. Autoimmune nodopathy patients with IgG4 anti–NF155 and anti–CNTN1 antibodies are also regarded as representatives of IgG4 autoimmune diseases (IgG4–AID), an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. Members of IgG4–AID, such as glomerulonephritis, pemphigus vulgaris, myasthenia gravis, and autoimmune encephalitis, share relevant immunobiological and therapeutic aspects even though different antigens, tissues, and organs are affected. Because IgG4 is immunologically inert, patients’ IgG4 subclass autoantibodies hypothetically block protein–protein interactions.

Autoimmune nodopathy patients with either antibody commonly show sensory ataxia, severe demyelination on nerve conduction studies, very high cerebrospinal protein levels, and detachment of terminal loops from the axolemma at the node of Ranvier in biopsied sural nerves. While younger age at onset and higher frequency of tremor are characteristic of anti–NF155 antibody–positive nodopathy, anti–CNTN1 antibody–positive nodopathy is characterized by higher age at onset, early axonal damage, aggressive subacute course, and concurrence of membranous nephropathy.