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• W2084345825 abstract "Across the breadth of autoimmune rheumatic diseases, there is a striking association of specific autoantibodies with distinct clinical phenotypes, making them excellent tools for classifying patients and predicting disease course and outcomes. Within the myositis spectrum, there are numerous examples of this. More than 2 decades ago, it was noted that autoantibodies against the aminoacyl–transfer RNA synthetases (the most frequently targeted of which is Jo-1) are found in myositis patients with a constellation of symptoms known as the “synthetase syndrome” (1,2). These include mechanic’s hands, interstitial lung disease, inflammatory arthritis, Raynaud’s phenomenon, and fever. A more recently described specificity is that of melanoma differentiation–associated protein 5 (MDA-5). Antibodies to MDA-5 are found in dermatomyositis (DM) patients with mild/absent muscle disease and are frequently associated with rapidly progressive interstitial lung disease (3). New data continue to further define the clinical phenotype associated with anti–MDA-5 antibodies; in a study of DM patients seen at an outpatient dermatology clinic, our group demonstrated that this specificity is associated with cutaneous ulcerations and distinctive palmar papules, and confirmed the association with rapidly progressing lung disease (4). These 2 examples confirm that autoantibodies in DM patients are of clinical utility. Autoantibodies against a protein doublet termed “p155/140” (denoting the molecular weights) define another distinct group of DM patients—those with an increased incidence of cancer compared to DM patients without malignancies (5). A meta-analysis of several studies confirmed that the presence of these autoantibodies has 70% sensitivity and 89% specificity for identifying patients with cancer-associated DM (6). This immune response appears specific to DM, as it is not found in patients with systemic sclerosis, lupus erythematosus, or healthy individuals. In 2006, p155 was identified as transcription intermediary factor 1 (TIF-1 ) by Targoff et al (7), but the identity of the 140-kd specificity remained elusive. The current study by Fujimoto et al, reported in this issue of Arthritis & Rheumatism (8), confirms the identity of p155 as TIF-1 (consistent with Targoff and colleagues’ findings described above) and also identifies the 140-kd antibody target as TIF-1 . The study also shows that TIF-1 (100 kd) is targeted in DM patients, although less frequently than its TIF-1 and TIF-1 counterparts. The TIF-1 specificities occurred alone (in the case of TIF-1 and TIF-1 , but not TIF-1 ) or in various combinations of TIF-1 , TIF-1 , and TIF-1 ; of the 78 DM patients studied by Fujimoto et al, 62% had anti–TIF-1 and anti–TIF-1 , 29% had anti– TIF-1 alone, 5.1% had antibodies to all 3 proteins, 2.6% had anti–TIF-1 and anti–TIF-1 , and 1.3% had anti–TIF-1 alone. Since these proteins are highly homologous, and because anti–TIF-1 frequently occurs alone while anti–TIF-1 never does, one possibility is that the epitope is a TIF-1 sequence, with crossreactivity of the antibodies to TIF-1 . Interesting in this regard is the fact that TIF-1 and TIF-1 share much more sequence similarity than with TIF-1 , perhaps explaining why anti–TIF-1 antibodies are so infrequently detected. These DM-specific antibodies are relatively frequent, being found in 17% of DM patients (78 of 456) in the study by Fujimoto et al. They constitute significant subsets in juvenile DM and adult cancer-associated DM Supported by the NIH (grant R01-AR-44684 to Dr. CasciolaRosen). David Fiorentino, MD, PhD: Stanford University School of Medicine, Stanford, California; Livia Casciola-Rosen, PhD: Johns Hopkins University School of Medicine, Baltimore, Maryland. Address correspondence to Livia Casciola-Rosen, PhD, Johns Hopkins University School of Medicine, Division of Rheumatology, 5200 Eastern Avenue, Mason F. Lord Building, Center Tower Suite 5300, Baltimore, MD 21224. E-mail: lcr@jhmi.edu. Submitted for publication September 22, 2011; accepted in revised form October 4, 2011." @default.
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• W2084345825 date "2012-01-27" @default.
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• W2084345825 title "Autoantibodies to transcription intermediary factor 1 in dermatomyositis shed insight into the cancer-myositis connection" @default.
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