Autoantibodies

Introduction
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By Joel Oger MD and Luca Durelli MD

Autoantibodies are antibodies that the body makes against its own components and thereby cause diseases or symptoms.  They play a role in a variety of neurologic disorders, including multiple sclerosis.  Patients receiving interferon beta treatment for multiple sclerosis are prone to developing autoantibodies. -ed.

In this clinical summary, Dr. Durelli reviews the role of autoreactive antibodies in a number of neurologic conditions. The antibodies that are directly responsible for pathogenesis of neurologic diseases, such as acetylcholine receptor antibodies or anticardiolipin antibodies, are rare. Most often these autoantibodies are a marker for specific neurologic disorders, as seen in paraneoplastic syndromes. In multiple sclerosis, an autoimmune disease involving the CNS, specific autoantigens have not yet been identified. A variety of autoreactive antibodies, including anticardiolipin, antinuclear, anti-SSA, and antithyroid antibodies, which are usually associated with specific vasculitic or systemic syndromes, can, however, be found in multiple sclerosis patients. Antibodies to interferon occur in treated multiple sclerosis patients, and their role is not clear. Autoreactive antibodies found in polyneuropathies are rarely diagnostic, besides anti-GQ1b antibodies in Miller-Fisher syndrome and antimyelin-associated glycoprotein antibodies in chronic inflammatory demyelinating neuropathy with IgM monoclonal gammopathy of unknown significance. In paraneoplastic neurologic syndromes several autoreactive antibodies associated with onconeuronal intracellular or intranuclear antigens are often suggestive of a specific cancer. Their early detection and treatment of underlying tumor may lead to clinical improvement in some cases. On the other hand, auto-reactive antibodies against surface or synaptic antigens are specific of certain neurologic syndromes that often respond to immunosuppressive treatment.

Key Points

  • In diseases such as myasthenia gravis, the antibodies that are measured are extremely specific to the disease and are pathogenic. Antibody-negative myasthenia gravis should be renamed “myasthenia gravis due to yet-to-be-discovered antibodies.”
  • Similarly, antibodies to cell surface receptors are found in paraneoplastic disorders such as limbic encephalitis, Lambert-Eaton syndrome, or their idiopathic equivalent. In these conditions, antibodies are most probably responsible for signs and symptoms.
  • Antibodies typically found in rheumatologic disorders, such as lupus and Sjögren syndrome, can also be found at low levels in some of the chronic inflammatory neurologic diseases, such as chronic encephalopathies, recurrent transverse myelitis, and multiple sclerosis; in many cases, they are probably an epiphenomenon.
  • Specific anti-aquaporin-4 antibodies in neuromyelitis optica have led to splitting them from multiple sclerosis and have brought attention to a new type of pathophysiology for optic neuritis and transverse myelitis.

In This Article

Introduction
Historical note and nomenclature
Description
Clinical applications
References cited
Contributors