Autoantibodies, Cancer, and Dermatomyositis
Fiorentino DF, Chung LS, Christopher-Stine L, et al
Arthritis Rheum. 2013;65:2954-2962
The association between adult-onset dermatomyositis (DM) and cancer is well known, with a prevalence of up to 30% in some studies. However, the exact mechanisms that explain this association, or the means to identify patients with cancer-associated DM, have been elusive.
In this article, Fiorentino and colleagues report their findings of antibodies to 2 antigens: nuclear matrix protein NXP-2 and transcription intermediary factor 1 gamma (TIF1-gamma) in patients with DM.
They evaluated 213 patients with DM from 2 institutions. All patients had undergone age-appropriate cancer screening or CT of the chest, abdomen, and pelvis. All cancers identified through these processes were confirmed with tissue diagnosis, and patients were classified as having cancer-associated DM if they had a cancer identified 3 years before or after the first onset of symptoms attributed to DM (although approximately 30% of patients were followed for < 3 years after the diagnosis of DM).
Antibodies to NXP-2 and TIF1-gamma were assessed using immunoprecipitation, with positivity determined on the basis of presence of an antibody by gel immunoblotting. Of note, the investigators report that this method has an advantage over other methods in that it is able to specifically identify antibody to these antigens.
Overall, cancer-associated DM was present in 29 of 213 patients (approximately 14%). A wide variety of cancers were reported, including breast, colorectal, renal cell, and thyroid.
Positivity for antibody to NXP-2 or TIF1-gamma was present in 55% of patients. Specifically, 17% of patients had antibody to NXP-2, and 38% to TIF1-gamma; only 2 patients were positive for both antibodies. Of note, a high proportion of patients who were positive for NXP-2 or TIF1-gamma (or both) antibodies were not positive for other myositis-associated antibodies, including anti-Mi-2 and transfer RNA synthetases.
Anti-NXP-2 or anti-TIF1-gamma was present in 83% of patients with cancer-associated DM, compared with 51% of patients without detectable cancer, although formal results for diagnostic accuracy of these antibodies for cancer were not presented. Neither of the 2 patients who were positive for both antibodies had cancer.
In multivariate analyses that were adjusted for age and sex, positivity for antibodies to both NXP-2 or TIF1-gamma was associated with an increased risk for cancer (odds ratio 3.8; P =.01), although positivity for each antibody separately was not. Furthermore, in stratified analyses, antibodies to NXP-2 were associated with an increased risk for cancer in men (odds ratio 5.8; P = .02). The investigators did not evaluate associations between these antibodies and specific cancers (eg, breast, colorectal).
Overall, and in keeping with previous studies, rates of cancer in these patients were highest among those older than 60 years. In patients with DM who were younger than 60 years and negative for antibody to NXP-2 and TIF1-gamma, the prevalence of cancer was low (approximately 3%).
Fiorentino and colleagues concluded that antibodies to NXP-2 and TIF1-gamma are frequently seen in patients with DM and are present in most patients with cancer-associated DM. They acknowledge that these results will need to be verified in additional populations, and that further work needs to be done to determine the clinical use of these antibodies.
Most Patients With Cancer-associated Dermatomyositis Have Antibodies to Nuclear Matrix Protein NXP-2 or Transcription Intermediary Factor 1 Gamma
Fiorentino DF, Chung LS, Christopher-Stine L, et al
Arthritis Rheum. 2013;65:2954-2962
Study Summary
The association between adult-onset dermatomyositis (DM) and cancer is well known, with a prevalence of up to 30% in some studies. However, the exact mechanisms that explain this association, or the means to identify patients with cancer-associated DM, have been elusive.
In this article, Fiorentino and colleagues report their findings of antibodies to 2 antigens: nuclear matrix protein NXP-2 and transcription intermediary factor 1 gamma (TIF1-gamma) in patients with DM.
They evaluated 213 patients with DM from 2 institutions. All patients had undergone age-appropriate cancer screening or CT of the chest, abdomen, and pelvis. All cancers identified through these processes were confirmed with tissue diagnosis, and patients were classified as having cancer-associated DM if they had a cancer identified 3 years before or after the first onset of symptoms attributed to DM (although approximately 30% of patients were followed for < 3 years after the diagnosis of DM).
Antibodies to NXP-2 and TIF1-gamma were assessed using immunoprecipitation, with positivity determined on the basis of presence of an antibody by gel immunoblotting. Of note, the investigators report that this method has an advantage over other methods in that it is able to specifically identify antibody to these antigens.
Overall, cancer-associated DM was present in 29 of 213 patients (approximately 14%). A wide variety of cancers were reported, including breast, colorectal, renal cell, and thyroid.
Positivity for antibody to NXP-2 or TIF1-gamma was present in 55% of patients. Specifically, 17% of patients had antibody to NXP-2, and 38% to TIF1-gamma; only 2 patients were positive for both antibodies. Of note, a high proportion of patients who were positive for NXP-2 or TIF1-gamma (or both) antibodies were not positive for other myositis-associated antibodies, including anti-Mi-2 and transfer RNA synthetases.
Anti-NXP-2 or anti-TIF1-gamma was present in 83% of patients with cancer-associated DM, compared with 51% of patients without detectable cancer, although formal results for diagnostic accuracy of these antibodies for cancer were not presented. Neither of the 2 patients who were positive for both antibodies had cancer.
In multivariate analyses that were adjusted for age and sex, positivity for antibodies to both NXP-2 or TIF1-gamma was associated with an increased risk for cancer (odds ratio 3.8; P =.01), although positivity for each antibody separately was not. Furthermore, in stratified analyses, antibodies to NXP-2 were associated with an increased risk for cancer in men (odds ratio 5.8; P = .02). The investigators did not evaluate associations between these antibodies and specific cancers (eg, breast, colorectal).
Overall, and in keeping with previous studies, rates of cancer in these patients were highest among those older than 60 years. In patients with DM who were younger than 60 years and negative for antibody to NXP-2 and TIF1-gamma, the prevalence of cancer was low (approximately 3%).
Fiorentino and colleagues concluded that antibodies to NXP-2 and TIF1-gamma are frequently seen in patients with DM and are present in most patients with cancer-associated DM. They acknowledge that these results will need to be verified in additional populations, and that further work needs to be done to determine the clinical use of these antibodies.