Session Type: Abstract Submissions (ACR)
Dermatomyositis (DM) is known to be associated with internal malignancy, and identifying patients at high risk is a high priority. Recently, several groups have shown that patients with circulating autoantibodies directed against transcriptional intermediary factor (TIF) isoforms are at increased risk of malignancy. In these studies, anti-TIF antibody positive patients were identified by immunoprecipitation of 140 kD and/or 155 kD proteins from radiolabeled cell lysates. However, this methodology can have suboptimal sensitivity and specificity. This might explain why the sensitivity and specificity of such assays for detecting those patients with cancer-associated DM varies widely in the literature. We wished to use novel sensitive assays to test if anti-TIF-g (or other) autoantibodies were associated with malignancy.
We designed, optimized and validated novel, sensitive, and highly specific assays to detect antibodies, including those against TIF-g and NXP-2. To detect TIF-g antibodies, HeLa cells were transiently transfected with the appropriate cDNA, resulting in expression levels 33-62 fold above endogenous levels. Immunoprecipitations were performed using these transfected lysates, electrophoresed on SDS-polyacrylamide gels, transferred to nitrocellulose and immunoblotted with an anti-TIF-g monoclonal antibody. NXP-2 antibodies were assayed by immunoprecipitation using 35S-methionine labeled NXP-2 generated by in vitro transcription-translation as source material. Patient sera from two DM cohorts seen at the Stanford University Dermatology Outpatient Clinic (n = 111) and the Johns Hopkins University Myositis Center (n = 102) were tested for antibodies against TIF-g and NXP-2 using these assays. We used logistic regression to estimate odds ratios for cancer.
The cohorts were similar in terms of age, gender, ethnicity distribution, as well as proportions of clinically amyopathic patients, and frequency of antibodies against NXP-2 and TIF-g. In the combined group, 17.3% and 36.2% of patients had antibodies against NXP-2 and TIF-g, respectively. Cancer was associated with DM in 35/213 (16.4%) of patients. In the group of 35 cancer patients, 11 (31.4%), 16 (45.7%) and 8 (22.9%) had antibodies against NXP-2, TIF-g, or neither. Thus, reactivity against either NXP-2 or TIF-g identified 77% of patients with cancer-associated DM. On univariate analysis, the odds ratios for cancer in patients with antibodies to NXP-2, TIF-g, or either were 2.6 (95% CI 1.1-6.0, p=0.022), 1.6 (95% CI 0.77-3.3, p=0.212), and 3.6 (95% CI 1.6-8.5, p=0.0027), respectively. This association between cancer and having either NXP-2 or TIF-g antibodies remained significant on multivariate analysis when corrected for other variables (age, gender, ANA, rash on back) that were associated with cancer in univariate analyses.
Conclusion: In this study using 2 large, well defined adult DM cohorts, and novel, highly specific assays to detect antibodies against TIF-g and NXP-2, we show that both of these antibody specificities are associated with an increased risk for cancer in patients with DM.
Gilead and Actelion,
Gilead, Actelion, Pfizer, United Therapeutics,
A. L. Mammen,
anti-HMGCR antibody test,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibodies-to-nxp-2-and-transcriptional-intermediary-factor-gamma-identify-patients-with-cancer-associated-dermatomyositis/