Autoantibodies to transcription intermediary factor (TIF)1β associated with dermatomyositis
1 Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, P.O.Box 100221, 1600 SW Archer Rd, Gainesville, FL 32610-0221, USA
2 Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, P.O.Box 100221, 1600 SW Archer Rd, Gainesville, FL 32610-0221, USA
3 Department of Oral Biology, University of Florida, P.O.Box 100424, 1600 SW Archer Rd, Gainesville, FL 32610-0424, USA
4 Division of Rheumatology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan
5 Departamento de Biología Molecular y Genómica, Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara, Jalisco, CP 44340, México
6 División de Medicina Interna, Departamento de Reumatología, Hospital Civil 'Dr. Juan I. Menchaca', Salvador de Quevedo y Zubieta N° 750, CP 44340, Guadalajara, Jalisco, México
7 Direction of Education and Research, Hospital de Especialidades 'Dr. Antonio Fraga Mouret', Centro Médico Nacional 'La Raza', IMSS, Seris/Zaachila s/n, Colonia La Raza, Delegación Azcapotzalco, CP 02990, Mexico City, México
8 Universidad Nacional Autónoma de México, Avenida Universidad 3000, Delegación Coyoacán, CP 04510, Mexico City, México
9 Department of Rheumatology, Hospital de Especialidades 'Dr. Antonio Fraga Mouret', Centro Médico Nacional 'La Raza', IMSS, Seris/Zaachila s/n, Colonia La Raza, CP 02990, Mexico City, México
Arthritis Research & Therapy 2012, 14:R79 doi:10.1186/ar3802Published: 18 April 2012
Myositis specific autoantibodies are associated with unique clinical subsets and are useful biomarkers in polymyositis/dermatomyositis (PM/DM). A 120 kD protein recognized by certain patients with DM was identified and clinical features of patients with this specificity were characterized.
The 120 kD protein recognized by a prototype serum was purified and identified by mass spectrometry and immunological methods. Autoantibody to this 120 kD protein was screened in sera from 2,356 patients with various diagnoses from four countries, including 254 PM/DM, by immunoprecipitation of 35S-methionine labeled K562 cell extracts. Clinical information of patients with this specificity was collected.
The 120 kD protein, which exactly comigrated with PL-12, was identified as transcription intermediary factor TIF1β (TRIM28) by mass spectrometry and validated by immunoassays. By immunofluorescence, anti-TIF1β positivity showed a fine-speckled nuclear staining pattern. Four cases of anti-TIF1β were identified; all are women, one each in a Japanese, African American, Caucasian, and Mexican individual. Three had a diagnosis of DM and one case was classified as having an undifferentiated connective tissue disease with an elevated CPK but without significant muscle symptoms. This individual also had a history of colon cancer, cervical squamous metaplasia and fibroid tumors of the uterus. Myopathy was mild in all cases and resolved without treatment in one case. The anti-TIF1β specificity was not found in other conditions.
Anti-TIF1β is a new DM autoantibody associated with a mild form of myopathy. Whether it has an association with malignancy, as in the case of anti-TIF1γ, or other unique features will need to be evaluated in future studies.