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Autoantibodies in Canine Masticatory Muscle Myositis Recognize a Novel Myosin Binding Protein-C Family Member

Xiaohua Wu^*,, Zhi-fang Li, Randolph Brooks^*, Elizabeth A. Komives, Justin W. Torpey, Eva Engvall, Steven L. Gonias^* and G. Diane Shelton^1,*

^* Department of Pathology, University of California, San Diego 92101; McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, NC 28203; Burnham Institute for Medical Research, La Jolla, CA 92037; and Department of Chemistry and Biochemistry, University of California, San Diego, CA 92101

Inflammatory myopathies are a group of autoimmune diseases that affect muscles. In humans, the most common inflammatory myopathies are polymyositis, dermatomyositis, and inclusion body myositis. Autoantibodies may be found in humans with inflammatory myopathies, and these play an important role in diagnosis and disease classification. However, these Abs are typically not muscle specific. Spontaneously occurring canine inflammatory myopathies may be good parallel disorders and provide insights into human myositis. In dogs with inflammatory myopathy, muscle-specific autoantibodies have been found, especially in masticatory muscle myositis. We have identified the major Ag recognized by the autoantibodies in canine masticatory muscle myositis. This Ag is a novel member of the myosin binding protein-C family, which we call masticatory myosin binding protein-C (mMyBP-C). mMyBP-C is localized not only within the masticatory muscle fibers, but also at or near their cell surface, perhaps making it accessible as an immunogen. The gene for mMyBP-C also exists in humans, and mMyBP-C could potentially play a role in certain human inflammatory myopathies. Understanding the role of mMyBP-C in this canine inflammatory myopathy may advance our knowledge of mechanisms of autoimmune inflammatory muscle diseases, not only in dogs, but also in humans.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. G. Diane Shelton, Department of Pathology, University of California, San Diego, La Jolla, CA 92093-0709. E-mail address: gshelton{at}ucsd.edu

² Abbreviations used in this paper: IM, inflammatory myopathy; PM, polymyositis; CMMM, canine masticatory muscle myositis; MyBP-C, myosin binding protein-C; mMyBP-C, masticatory MyBP-C; TTBS, Tween 20 Tris buffered saline; MS, mass spectrometry.