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1.
J Immunol ; 179(7): 4939-44, 2007 Oct 01.
Article in English | MEDLINE | ID: mdl-17878394

ABSTRACT

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.


Subject(s)
Autoantibodies/immunology , Carrier Proteins/classification , Carrier Proteins/immunology , Masticatory Muscles/immunology , Myositis/immunology , Actins/metabolism , Amino Acid Sequence , Animals , Carrier Proteins/chemistry , Carrier Proteins/genetics , DNA, Complementary/genetics , Disease Models, Animal , Dog Diseases/genetics , Dog Diseases/immunology , Dog Diseases/metabolism , Dogs , Dystrophin/metabolism , Humans , Masticatory Muscles/metabolism , Molecular Sequence Data , Molecular Weight , Myositis/genetics , Myositis/metabolism , Myositis/veterinary , Protein Binding , Sequence Alignment , Sequence Homology, Amino Acid
3.
Muscle Nerve ; 33(2): 215-24, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16270307

ABSTRACT

Masticatory muscle myositis (MMM) is the most common inflammatory myopathy (IM) in dogs, associated with antibodies against myosin. To further elucidate the immunopathogenesis, we investigated muscles of 53 dogs with MMM, 32 dogs with polymyositis (PM), and 4 dogs suffering from both, with regard to the presence and location of CD4(+) and CD8(+)T cells, B cells, macrophages, major histocompatibility complex (MHC) class I and class II antigens, and autoantibodies. CD8(+)T cells were found in MMM (91%) and PM (75%), mostly paralleled (68% and 61%) by enhanced expression of MHC class I antigen on muscle fibers. CD8(+)T cells invading intact and neighboring necrotic muscle fibers were present in MMM (39%) and PM (42%). Dogs with MMM lacking intramuscular (26%) and circulating (36%) autoantibodies also had CD8(+) T-cell infiltrations and muscle-fiber lesions. Since MHC class I antigen and CD8(+) T cells were detected in the presence of CD4(+) T cells, regardless of antimuscular antibodies, we consider MMM and PM in the dog as a CD8(+) T-cell-mediated immunopathological disease that initiates muscle-fiber destruction and leads to production of myosin autoantibodies.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Dog Diseases/immunology , Major Histocompatibility Complex/immunology , Masticatory Muscles/immunology , Myositis/veterinary , Polymyositis/veterinary , Animals , Autoantibodies/immunology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/physiology , CD8-Positive T-Lymphocytes/pathology , Dog Diseases/physiopathology , Dogs , Female , Genes, MHC Class I , Genes, MHC Class II , Immunoglobulin G/analysis , Immunohistochemistry , Immunophenotyping , Macrophages/immunology , Macrophages/pathology , Major Histocompatibility Complex/genetics , Major Histocompatibility Complex/physiology , Male , Masticatory Muscles/physiopathology , Muscle Fibers, Skeletal/immunology , Muscle Fibers, Skeletal/pathology , Myosins/immunology , Myositis/immunology , Myositis/physiopathology , Polymyositis/immunology , Polymyositis/physiopathology
4.
Proc Natl Acad Sci U S A ; 98(21): 12062-7, 2001 Oct 09.
Article in English | MEDLINE | ID: mdl-11572940

ABSTRACT

Skeletal muscle fibers are defined by patterned covariation of key traits that determine contractile and metabolic characteristics. Although the functional properties of most skeletal muscles result from their proportional content of a few conserved muscle fiber types, some, typically craniofacial, muscles exhibit fiber types that appear to lie outside the common phenotypic range. We analyzed gene expression profiles of three putative muscle classes, limb, masticatory, and extraocular muscle (EOM), in adult mice by high-density oligonucleotide arrays. Pairwise comparisons using conservative acceptance criteria identified expression differences in 287 genes between EOM and limb and/or masticatory muscles. Use of significance analysis of microarrays methodology identified up to 400 genes as having an EOM-specific expression pattern. Genes differentially expressed in EOM reflect key aspects of muscle biology, including transcriptional regulation, sarcomeric organization, excitation-contraction coupling, intermediary metabolism, and immune response. These patterned differences in gene expression define EOM as a distinct muscle class and may explain the unique response of these muscles in neuromuscular diseases.


Subject(s)
Gene Expression , Oculomotor Muscles/metabolism , Animals , Gene Expression Profiling , Male , Masticatory Muscles/immunology , Masticatory Muscles/metabolism , Mice , Mice, Inbred C57BL , Muscle, Skeletal/immunology , Muscle, Skeletal/metabolism , Neuromuscular Diseases/genetics , Oculomotor Muscles/immunology , Oligonucleotide Array Sequence Analysis/methods , Phenotype , Signal Transduction , Transcription Factors/genetics
5.
J Orofac Pain ; 9(2): 131-7, 1995.
Article in English | MEDLINE | ID: mdl-7488982

ABSTRACT

Interleukin-6-dependent mouse hybridoma cell line KD83 was used to test the biologic activity of interleukin-6 in synovial fluid from 37 patients with temporomandibular disorders. The results showed that the interleukin-6 level was greater than 100 U/mL in 13 of 18 patients with degenerative joint disease and in five of 12 patients with temporomandibular disc displacement. However, the interleukin-6 level was less than 100 U/mL (range, 20 to 75 U/mL) in all patients with masticatory muscle disorder. It has been found that degenerative joint disease tends to have acute and chronic stages, and interleukin-6 activity was probably related to the acute stage in the patients. Histologic studies of the synovium from seven patients with degenerative joint disease showed a variable degree of hyperplasia of the synovial lining cells and chronic inflammation in five of eight specimens. Immunostaining studies clearly showed the presence of significantly more HLA-DR-expressing cells (human leukocyte antigen-D-related) in synovium. Although it is unlikely that immune responses play an important primary role in initiating synovial inflammation and cartilage destruction, immune reactions may be one important factor in the maintenance and severity of some patients with temporomandibular disorders.


Subject(s)
HLA-DR Antigens/immunology , Interleukin-6/biosynthesis , Synovial Fluid/immunology , Synovitis/immunology , Temporomandibular Joint Disorders/immunology , Adolescent , Adult , Animals , Cartilage, Articular/pathology , Chronic Disease , Facial Pain/etiology , Facial Pain/immunology , Female , HLA-DR Antigens/analysis , Humans , Interleukin-6/immunology , Joint Dislocations/pathology , Male , Mandibular Condyle/pathology , Masticatory Muscles/immunology , Mice , Middle Aged , Osteoarthritis/immunology , Rabbits , Range of Motion, Articular , Synovial Membrane/immunology , Temporomandibular Joint Disorders/complications , Temporomandibular Joint Dysfunction Syndrome/complications , Temporomandibular Joint Dysfunction Syndrome/immunology
6.
Muscle Nerve ; 10(8): 753-66, 1987 Oct.
Article in English | MEDLINE | ID: mdl-3317035

ABSTRACT

The histopathologic features in temporalis muscle biopsies from 29 dogs with masticatory muscle disorders were characterized and used for their subgrouping: 2 without lesions, 3 with nonspecific changes, 7 with neurogenic atrophy, and 16 with myositis. The immunocytochemical and immunochemical features of the muscle biopsies and sera from those dogs were compared among the histopathologic subgroupings and compared with biopsies and sera from healthy dogs and dogs with polymyositis. Of the 14 biopsies from dogs with masticatory muscle myositis, 12 had immune complexes limited to type 2M fibers, whereas 13 of 16 sera samples had detectable antibodies against type 2M fibers. The immune complex deposition was found only in biopsies of dogs with masticatory muscle myositis, and the antibodies were detected in the sera of only one dog that did not have masticatory muscle myositis. Immunoblot assays revealed that the antibodies were most often directed against a 185 K protein, myosin heavy chain, and a band that appeared to be LC2-M (myosin light chain 2-masticatory).


Subject(s)
Autoantibodies/analysis , Autoimmune Diseases/pathology , Masticatory Muscles/pathology , Muscle Proteins/immunology , Neuromuscular Diseases/pathology , Animals , Autoimmune Diseases/immunology , Biopsy , Dogs , Enzyme-Linked Immunosorbent Assay , Immunoenzyme Techniques , Masticatory Muscles/immunology , Muscular Atrophy/pathology , Myositis/pathology , Neuromuscular Diseases/immunology
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