Serum Autoantibodies in Myasthenia Gravis and Thymoma: Selective Affinity for I-Bands of Striated Muscle As a Guide to Identification of Antigen(s)

Abstract

A panel of sera from 90 persons was studied with respect to sites of binding of γ-globulins to striated muscle in vitro. The indirect and direct fluorescent antibody techniques were employed and compared. Sera from 51 individuals including 47 selected patients with myasthenia gravis, when tested with the indirect technique, reacted consistently with skeletal muscle I-bands in cryostat sections and myofibril suspensions of bovine, human and rabbit origin in a titer range 1:120 to 1:1920. H-zone (M-line) staining was a frequent associated finding. Sera from 49 control individuals reacted with the same morphologic loci, within limits determinable by light microscopic techniques, in a titer range 1:15 to 1:30. Individual and pooled serum globulins from patients with myasthenia gravis, which had been conjugated directly with fluorescein isothiocyanate, also reacted with I-bands and H-zones in a titer range 1:40 to 1:80. Directly conjugated serum globulins from normal controls failed to produce striational staining. The pattern of staining seen with both indirect and direct fluorescent antibody techniques strongly resembles that produced upon treatment of striated muscle with fluorescent antibodies against purified actin and tropomyosin. The present findings strongly suggest that A-band and Z-line staining with human sera on a specific immunologic basis, as described or inferred in previous reports, is an uncommon effect, if indeed it occurs at all. It is more likely that previous descriptions or interpretations of A-band staining by sera from patients with myasthenia gravis can be explained on the basis of procedural flaws and limitations. The possible staining of narrow zones of A-bands immediately adjacent to stained I-bands cannot be totally excluded because of the limits of resolution of the fluorescent antibody technique.