Titin and ryanodine receptor autoantibodies in dogs with thymoma and late-onset myasthenia gravis

Similar to human autoimmune myasthenia gravis (MG), canine MG occurs sponta neously and is associated with autoantibodies against the nicotinic acetylc holine receptor (AChR). In addition to AChR, human MG patients with thymoma or late-onset MG have antibodies against titin and ryanodine receptor (RyR ). The objective of this study was to establish if dogs with confirmed MG ( AChR antibody titer >0.6 nmol/l) also developed titin and RyR antibodies an d identify possible associations with thymoma, late age of onset, or severi ty of clinical signs. Sera from dogs (n = 430) with previously diagnosed au toimmune MG (N = 415), other immune-mediated neuromuscular disorders includ ing polymyositis (PM) and masticatory muscle myositis (N = 5), and control dogs (N = 10) were evaluated for the presence of titin antibodies in ELISA using MGT-30 as antigen, a peptide representing the main immunogenic region (MIR) for human titin antibodies. Titin antibody positive sera were furthe r examined for RyR antibodies in Western blots using a RyR fusion protein ( pc2-RyR) as antigen, which covers the MIR for human MG sera. Titin antibodi es were found in sera of 80/430 dogs. Thymoma was present in 11/80 and age of onset was after 4 years in 66/80 titin positive dogs. Two of the titin p ositive dogs had PM. RyR antibodies were found in 13/80 sera (8/13 thymoma, 12/13 age of onset after 4 years, and 1/13 PM). Neither titin nor RyR anti bodies were found in sera of healthy control dogs. Acute fulminating MG was described in five dogs with both titin and RyR antibodies. From these stud ies we conclude that titin and RyR antibodies in canine and human MG have a similar association with thymoma, late-onset MG, and possibly with more se vere forms of MG. (C) 2001 Elsevier Science B.V. All rights reserved.