Something in the Blood? A History of the Autoimmune Hypothesis regarding Myasthenia Gravis

Abstract

From the first descriptions of myasthenia gravis (MG) in the late nineteenth century, speculation about the cause of MG has centered on the possibility of some curare-like factor circulating in the blood. The transfer of transient myasthenic symptoms from a myasthenic mother to her newborn reinforced this speculation. However, it was not until 1960, when William Nastuk and coworkers noted that serum complement correlated with the clinical course in MG, and Arthur Strauss and colleagues described antiskeletal muscle antibodies in the sera of some MG patients, that a paradigm shift occurred from prior exclusive focus on the neuromuscular junction to a broader consideration of the relevance of immunological mechanisms in myasthenia. These findings coincided with an even greater scientific revolution pioneered by Macfarlane Burnet towards cell-mediated and away from chemical immunology. The dominant immunological question of the decade 1955–1965, however, was whether human autoimmune diseases actually existed. During the next decade, 1965–1975, various diseases were accepted as being autoimmune in character, and although comparatively rare, MG became prominent among them because of a known antigen, the acetylcholine receptor, and an excellent experimental model.

Keywords:

• myasthenia gravis
• circulating factor
• autoimmune
• complement
• muscle antibodies
• thymus antibodies
• Witebsky postulates
• acetylcholine receptor

Notes

¹Initially Strauss and his colleagues (Strauss et al., 1961) claimed that myasthenic globulins bound at the A bands of skeletal muscles, but later (Strauss, 1968) Strauss agreed with the Glasgow pathologist, John Vetters, that myasthenic sera reacted primarily with the I bands (Vetters, 1965). Eventually, with immuno-electron-microscopy, the predominant muscle antigen was identified as titin, a giant filamentous protein that spans half a sarcomere (Aarli et al., 1990).