C1D is a major autoantibody target in patients with the polymyositis-scleroderma overlap syndrome. 2007

Geurt Schilders, and Wilma Vree Egberts, and Reinout Raijmakers, and Ger J M Pruijn
Nijmegen Center for Molecular Life Sciences, Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.

OBJECTIVE To assess whether the recently discovered exosome-associated proteins MPP6, C1D, KIAA0052/hMtr4, hSki2, and hSki8 are targeted by autoantibodies, and to determine whether these autoantibodies are accompanied by antibodies directed to the established exosome-associated autoantigens PM-Scl-75 and PM-Scl-100. METHODS Complementary DNAs encoding the recently identified human exosome-associated proteins were expressed as His-tagged fusion proteins in Escherichia coli cells. Sera obtained from patients with several different autoimmune diseases were analyzed for the presence of autoantibodies directed to these proteins, in an enzyme-linked immunosorbent assay (ELISA). The ELISA data obtained for C1D were confirmed by Western blot analysis, using recombinant C1D. RESULTS All exosome-associated proteins were found to be targeted by autoantibodies, although the frequency with which such antibodies occurred in patient sera was relatively low, with the exception of anti-C1D antibodies. Autoantibodies recognizing C1D were detected in 7 of 30 patients (23%) with the polymyositis (PM)-scleroderma overlap syndrome; this frequency was similar to the frequencies for the established autoantigens PM-Scl-75c (27%) and PM-Scl-100 (23%). Importantly, several patients with the PM-scleroderma overlap syndrome had anti-C1D antibodies but no anti-PM-Scl antibodies. Anti-C1D autoantibodies were observed in only 2 of 204 patients with other diseases, including PM, dermatomyositis, and scleroderma. CONCLUSIONS Our results demonstrate that the recently identified exosome-associated protein C1D is a major autoantigen in patients with the PM-scleroderma overlap syndrome and suggest that the use of recombinant C1D as an autoantibody target may aid in diagnosis of the PM-scleroderma overlap syndrome.

UI MeSH Term Description Entries
D012097 Repressor Proteins Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release. Repressor Molecules,Transcriptional Silencing Factors,Proteins, Repressor,Silencing Factors, Transcriptional
D003882 Dermatomyositis A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. (From Adams et al., Principles of Neurology, 6th ed, pp1405-6) Polymyositis-Dermatomyositis,Dermatomyositis, Adult Type,Dermatomyositis, Childhood Type,Dermatopolymyositis,Juvenile Dermatomyositis,Juvenile Myositis,Adult Type Dermatomyositis,Childhood Type Dermatomyositis,Dermatomyositis, Juvenile,Myositis, Juvenile,Polymyositis Dermatomyositis
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001323 Autoantibodies Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them. Autoantibody
D001324 Autoantigens Endogenous tissue constituents with the ability to interact with AUTOANTIBODIES and cause an immune response. Autoantigen,Autologous Antigen,Autologous Antigens,Self-Antigen,Self-Antigens,Antigen, Autologous,Antigens, Autologous,Self Antigen,Self Antigens
D012595 Scleroderma, Systemic A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA. Sclerosis, Systemic,Systemic Scleroderma,Systemic Sclerosis
D013577 Syndrome A characteristic symptom complex. Symptom Cluster,Cluster, Symptom,Clusters, Symptom,Symptom Clusters,Syndromes
D017285 Polymyositis Diseases characterized by inflammation involving multiple muscles. This may occur as an acute or chronic condition associated with medication toxicity (DRUG TOXICITY); CONNECTIVE TISSUE DISEASES; infections; malignant NEOPLASMS; and other disorders. The term polymyositis is frequently used to refer to a specific clinical entity characterized by subacute or slowly progressing symmetrical weakness primarily affecting the proximal limb and trunk muscles. The illness may occur at any age, but is most frequent in the fourth to sixth decade of life. Weakness of pharyngeal and laryngeal muscles, interstitial lung disease, and inflammation of the myocardium may also occur. Muscle biopsy reveals widespread destruction of segments of muscle fibers and an inflammatory cellular response. (Adams et al., Principles of Neurology, 6th ed, pp1404-9) Myositis, Multiple,Polymyositis Ossificans,Polymyositis, Idiopathic,Idiopathic Polymyositides,Idiopathic Polymyositis,Multiple Myositis,Myositides, Multiple,Ossificans, Polymyositis,Polymyositides,Polymyositides, Idiopathic
D056970 Co-Repressor Proteins A subclass of repressor proteins that do not directly bind DNA. Instead, co-repressors generally act via their interaction with DNA-BINDING PROTEINS such as a TRANSCRIPTIONAL SILENCING FACTORS or NUCLEAR RECEPTORS. Co-Repressor,Co-Repressor Protein,Corepressor,Corepressor Protein,Nuclear Hormone Receptor Co-Repressor,Nuclear Receptor Co-Repressor,Nuclear Receptor Corepressor,Co-Repressors,Corepressor Proteins,Corepressors,Nuclear Hormone Receptor Co-Repressors,Nuclear Receptor Co-Repressors,Nuclear Receptor Corepressors,Co Repressor,Co Repressor Protein,Co Repressor Proteins,Co Repressors,Co-Repressor, Nuclear Receptor,Co-Repressors, Nuclear Receptor,Corepressor, Nuclear Receptor,Corepressors, Nuclear Receptor,Nuclear Hormone Receptor Co Repressor,Nuclear Hormone Receptor Co Repressors,Nuclear Receptor Co Repressor,Nuclear Receptor Co Repressors,Protein, Co-Repressor,Protein, Corepressor,Receptor Co-Repressor, Nuclear,Receptor Co-Repressors, Nuclear,Receptor Corepressor, Nuclear
D018076 DNA, Complementary Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe. Complementary DNA,cDNA,cDNA Probes,Probes, cDNA

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