Session Type: Abstract Submissions (ACR)
Background/Purpose: Myositis [particularly dermatomyositis (DM)] is associated with cancer and anti-transcription intermediary factor-1 gamma (TIF1γ) is a serologic risk factor for cancer associated myositis (CAM). Anti-TIF1γ detection by immunoprecipitation (IP) is costly, time-consuming and research-based. We used a validated anti-TIF1γ ELISA to determine the frequency of this marker in a large prospective myositis cohort, to compare it with the identification of TIF1γ by IP and to determine whether quantitative anti-TIF1γ levels could identify CAM patients.
Methods: We analyzed a prospectively collected computer and serum database of adult myositis (n=856) patients to identify CAM patients with a non-skin (basal/squamous cell) cancer within 3 years (CAM3) or 5 years (CAM5) (before or after) the myositis diagnosis. A control group of polymyositis (PM), DM and overlap myositis (OM) patients without CAM matched 2:1 by gender and age (+/- 10 years) and with a minimum 5 year follow up was selected. Serum was assessed for anti-TIF1γ by ELISA and IP.
Results: Using anti-TIF1γ detection by IP as the gold standard, the ELISA had 91% sensitivity, 96% specificity, 93% positive predictive value (PPV) and 95% negative predictive value (NPV) for anti-TIF1γ detection. There were 34 and 22 PM CAM5 and CAM3 cases (26F/8M), respectively, and 69 PM (53F/16M) controls, who were anti-TIF1γ (-) by IP (n=32) and ELISA (n=22). Six OM CAM5 cases (4F/2M), 3 being CAM3, were also anti-TIF1γ (-) by IP and ELISA (n=5) and 15 OM controls were anti-TIF1γ (-) by IP (n=13) and ELISA (n=14) except for 1 SSc-PM overlap patient. Of 45 CAM3 DM patients (31F/14M), 34 (24F/10M; mean age 58) had anti-TIF1γ IP and ELISA testing along with 95 DM controls (59F/36M; mean age 47). Anti-TIF1γ by IP was (+) in 47% CAM3 and 23% controls with 47% sensitivity, 82% specificity, 50% PPV and 80% NPV. By comparison, anti-TIF1γ by ELISA showed similar test characteristics at a low (+) cutoff (6 units/ml) while higher specificity (98%) was noted with a high (+) (>100 units/ml) cutoff but with a loss of sensitivity (35%). The odds of CAM3 was 3-4x higher in patients with TIF1γ positivity by IP or ELISA, but 25x higher in patients with a high (+) ELISA. Similar results were seen for CAM5 DM. Most DM-CAM patients were diagnosed within 1 year (31/34) before or after the myositis diagnosis and 3 females with high (+) anti-TIF1γ ELISAs decreased markedly after cancer treatment on longitudinal follow up. A high (+) ELISA (>50units/ml) was common in breast, ovarian and lung cancers (13/24) and in CAM within 1 year of myositis diagnosis (6/12).
Conclusion: This is the first case-control study in CAM using anti-TIF1γ by IP and ELISA. Anti-TIF1γ was not seen in PM or OM with or without cancer, but was highly specific for DM. Anti-TIF1γ was also seen in non-CAM DM (23-32% depending on detection method) contrary to previous studies showing a specificity of >90% in DM-CAM. Moreover, ELISA has similar test characteristics to IP for anti-TIF1γ detection with greater specificity and likelihood (i.e. odds) to identify cancer in a myositis patient with high levels of anti-TIF1γ. Finally, longitudinal follow up of anti-TIF1γ by ELISA may be useful prognostically.
M. C. Levesque,
C. V. Oddis,
Genentech and Biogen IDEC Inc.,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-transcription-intermediary-factor-1-gamma-tif1-%cf%85-autoantibody-detection-by-elisa-and-immunoprecipitation-in-a-prospective-myositis-cohort-predictive-value-for-cancer-associated-myositis/