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

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 S-35-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 TIF1 beta (TRIM28) by mass spectrometry and validated by immunoassays. By immunofluorescence, anti-TIF1 beta positivity showed a fine-speckled nuclear staining pattern. Four cases of anti-TIF1 beta 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-TIF1 beta specificity was not found in other conditions. Conclusions: Anti-TIF1 beta 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-TIF1 gamma, or other unique features will need to be evaluated in future studies.