Changes in antibody titres in patients with anti-transcription intermediary factor 1-gamma antibody-positive idiopathic inflammatory myositis

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Anti-transcription intermediary factor 1-gamma antibody titres in treated DM patients varied with or without malignancies. Sir, Patients with PM/DM have a higher rate of cancer than the general population [1]. Anti-transcription intermediary factor 1-gamma (TIF1γ) antibodies have been reported to be related to cancer-associated myositis (CAM) [2]. Since cancer is one of the most important prognostic factors in PM/DM patients; it is important to evaluate the prevalence and characteristics of anti-TIF1γ antibody-positive patients. We analysed anti-TIF1γ antibody-positive PM/DM patients in terms of both clinical characteristics and changes in anti-TIF1γ antibody titres after treatment. We retrospectively examined patients who were admitted to Juntendo University Hospital from 2008 to 2017. One hundred and thirty-one patients were diagnosed with PM, DM or clinically amyopathic dermatomyositis according to the diagnostic criteria [3, 4]. We applied the most commonly used criterion for CAM: cancer detection within 3 years of PM/DM or clinically amyopathic dermatomyositis diagnosis [2]. We ultimately analysed 119 of the initial 131 patients because in the remaining patients, we were unable to obtain autoantibody profiles at the time. A malignancy survey was performed in all patients. Anti-TIF1γ antibody titres were measured by ELISA using the MESACUP anti-TIF1γ test. This study was approved by the ethical committee of Juntendo University Hospital. All patients provided written informed consent in accordance with the Declaration of Helsinki. Anti-TIF1γ antibodies were detected in eight patients (6.7%), with a median titre of 96 U/ml (IQR 87–101). Supplementary Table S1, available at Rheumatology online, shows the characteristics at diagnosis, treatment details on admission, and survival rates in the overall population and in the anti-TIF1γ antibody-positive and antibody-negative groups. Our results showed that anti-TIF1γ antibody levels should ideally be measured in idiopathic inflammatory myositis (IIM) patients with the following characteristics: older age, dermatitis positivity, negative cytoplasmic ANA staining pattern, and absence of interstitial lung disease. These characteristics were also identified in previous reports [5, 6]. In the anti-TIF1γ antibody-positive group, five patients (62.5%) were diagnosed with CAM, and seven patients (87.5%) had specific rash or dermatitis. The frequency of interstitial lung disease was significantly lower in the anti-TIF1γ antibody-positive group. Of the five CAM patients in the anti-TIF1γ antibody-positive group, two had lung cancer, one had ovarian cancer, one had pharyngeal cancer, and one had cancer of unknown primary site. Of the seven CAM patients in the anti-TIF1γ antibody-negative group, two had breast cancer, two had ovarian cancer, one had lung cancer, one had colon cancer, and one had thyroid cancer. Supplemental Table S2, available at Rheumatology online, shows the details of the CAM patients. Figure 1A shows the Kaplan–Meier curves for the anti-TIF1γ antibody-positive and antibody-negative groups. The results of the log-rank test for the two groups was P = 0.011, and the anti-TIF1γ antibody-positive group had a higher mortality rate. Overall, 12 patients died during the observation period, with the following causes of death: respiratory failure with interstitial lung disease in eight patients, colorectal perforation in two, sepsis in one, and pneumocystis pneumonia in one. Figure 1B shows the changes in anti-TIF1γ antibody titres in four patients in whom titres were measured over time. All four patients with IIM without malignancy entered remission within 6 months of treatment initiation. The anti-TIF1γ antibody titres in the CAM patients did not decrease, whereas those in IIM patients decreased to below the normal value. Survival curves and changes in anti-TIF1γ antibody titres (A) Kaplan–Meier curves for mortality, comparing the anti-TIF1γ antibody-positive and antibody-negative group. The results of the log-rank test for two groups was P = 0.011. (B) The change of the anti-TIF1γ antibody titre in four patients in which anti-TIF1γ antibody was measured over time. The normal titre of anti-TIF1γ antibody is < 32 U/ml (dotted line). TIF1γ: transcription intermediary factor 1-gamma; CAM: cancer associated myositis; IIM: idiopathic inflammatory myositis. In previous reports, 38–75% of patients with anti-TIF1γ antibody-positive IIM had CAM [2, 5], compared with 63% in this study. The prognosis of CAM patients is determined by the type and stage of the underlying malignancy [7]. A previous study reported that patients with breast cancer or thyroid cancer often have longer survival times than patients with other cancers in Japan [8]; this finding may have been relevant in our analysis, as of the seven CAM patients without anti-TIF1γ antibody, two had breast cancer and one had thyroid cancer. In this study, we reported the time course of changes in anti-TIF1γ antibody titres. A previous study found that anti-TIF1γ antibody titres were decreased by treatment in eight of nine patients [9], and another study showed that the median anti-TIF1γ antibody titre was decreased in 21 patients who were treated with rituximab [10]. In this study, anti-TIF1γ antibody titres were not decreased in CAM patients, whereas they fell below the normal value in IIM patients without malignancy. The failure of anti-TIF1γ antibody titres to decline after treatment raises the possibility of an underlying malignancy. The limitations of this study were the small number of patients and the retrospective, single-centre design. Because the MESACUP anti-TIF1γ test sometime provides false-positive results [9], we examined with the antibody absorption test (Supplemental Table S3, available at Rheumatology online). We demonstrated that anti-TIF1γ antibody titres did not decrease after treatment in CAM patients, but they did decrease in IIM patients without malignancy. In patients diagnosed with anti-TIF1γ antibody-positive IIM without malignancy, if anti-TIF1γ antibody titres increase after treatment, we recommend that physicians repeat malignancy screening. The authors would like to thank Medical and Biological Laboratories Co., Ltd for technical assistance with the antibody absorption test. Funding: No specific funding was received from any bodies in the public, commercial, or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: The authors have declared no conflicts of interest.