Autoantibodies to transcription intermediary factor (TIF)1β associated with dermatomyositis

• DOI: 10.1186/ar3802
• Publication Date: 2012-04-18T10:51:31Z
• Authors: Minoru Satoh; Jason YF Chan; Steven J Ross; Yi Li; Yoshioki Yamasaki; Hidehiro Yamada; Monica Vazquez-de...; Marcelo H Petri; Luis J Jara; Miguel A Saavedra; Claudia Cruz-Reyes; Eric S Sobel; Westley H Reeves; Angela Ceribelli; Edward KL Chan
• Keywords: 0301 basic medicine; Epidemiology; Molecular Sequence Data; Immunology; Dermatology; Tripartite Motif-Containing Protein 28; Genetic Disorders Causing Tissue Mineralization Abnormalities; Gene; Dermatomyositis; Hypereosinophilic Syndrome and Related Disorders; 03 medical and health sciences; Autoantibody; 0302 clinical medicine; Muscular Diseases; Rheumatology; Biochemistry, Genetics and Molecular Biology; Myositis-specific Antibodies; Health Sciences; Genetics; Immunology and Allergy; Humans; Amino Acid Sequence; Registries; Internal medicine; Biology; Antibody; Autoantibodies; FOS: Clinical medicine; Life Sciences; Epidemiology, Classification, and Clinical Features of Inflammatory Myopathies; 3. Good health; Repressor Proteins; FOS: Biological sciences; amino acid sequence; autoantibodies; biological markers; fermatomyositis; female; humans; K562 cells; molecular sequence data; muscular diseases; registries; repressor proteins; rheumatology; immunology; immunology and allergy; medicine (all); Medicine; Female; Transcription factor; K562 Cells; Biomarkers; Research Article

Abstract Introduction 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.

Methods 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.

Results 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.

Conclusions 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.