Spontaneous anti-interferon alpha antibodies in myasthenia gravis patients

Myasthenia gravis (MG) is caused by autoantibodies against the acetylcholine receptor (AChR) on the neuromuscular plaque. Several groups have reported this disease as a complication of interferon (IFN) alpha treatments. Ten (11.2%) and 6 (6.7%) sera were identified that contained positive competing and non-competing anti-IFN-alpha 2b auto-antibodies, respectively. The MG sera were further analyzed by immunobloting against reduced IFN alpha-2b and for neutralizing anti-IFN alpha activity in an anti-viral assay cells system. From tested EIA positive-competing sera, 5 were shown to be positive by immunoblot and 6 sera were found to contain neutralizing anti-IFN-alpha2b. Four of the 6 neutralizing anti-IFNalpha2b sera came from patients with thymoma-associated MG. The sera were studied for linear epitope recognition on the IFN-alpha2b molecule by a solid phase binding assay. Peptides number 2, 3, 6, 10, 15, and 21 were the immunoreactive. Peptide 21 was apparently associated with antiviral activity. These results indicate that neutralizing anti-IFN-alpha2b recognizes a variety of epitopes on the IFN alpha-2b molecule, including those involved in its biological activity. Some of these epitopes could be regions for cross-reaction with antibodies against the acetylcholine receptor a chain present in myasthenia gravis patients.