Background Antibodies against TIF1gamma have been detected in patients with cancer associated myositis (CAM) and might become a useful marker for this myositis entity. It is not known whether the antibodies precede the symptoms of cancer or if the antibodies persist after successful treatment of a malignancy. It is furthermore unknown if the level of positivity plays a role in the prognosis of patients with CAM.
Objectives To analyse the levels of TIF1gamma antibodies in longitudinally collected sera taken before cancer diagnosis and after treatment of the malignancy in patients with CAM, in particular to observe if the antibody is present before cancer diagnosis and if it disappears after cancer treatment.
Methods From the Karolinska Rheumatology myositis register including 170 myositis patients we found 56 cases of CAM. Serum samples and clinical data were available from 54 patients. The mean observation time from cancer diagnosis to death or last visit was 4.4 years. Serum levels of anti-TIF1gamma antibody were tested by ELISA using a commercially available purified recombinant protein (OriGene, Rockville, MD). The cut-off for positivity on ELISA was established at 0.209 absorbance units; that is 2 standard deviations above the mean value obtained from 10 healthy and 26 polymyositis controls.
Results Sera from 16 (29.6%) patients (13 females and 3 males) were positive for anti-TIF1gamma antibodies in at least one serum sample. Their mean age was 63.6 years. Of the 16 positive patients 12 had developed cancer within 3 years from myositis diagnosis, 4 after 3 years. 15 patients had solid tumors; the most frequent were 4 ovarial cancers, 2 breast cancers, and 3 lung cancers. Of the total 54 patients, serum samples taken before cancer diagnosis were available from 15 patients and four of them were positive for anti-TIF1gamma. One of these patients had detectable anti-TIF1gamma antibodies up to 5 years before cancer diagnosis. Of the 16 patients positive for anti-TIF1 gamma, 12 patients had died at time of our study, 7 within 1 year from cancer diagnosis. The 7 patients who died within one year had a mean antibody level of 1976 +/- 304 au, the 5 patients who died after more than 1 year had a mean antibody level of 1036 +/- 555 au (p=0.003). None of the patients that died became negative in the antibody test after cancer diagnosis. Four patients were still alive at time of the investigation, between 2-13 years after cancer treatment. They were all in remission from cancer disease. Two patients became negative for anti-TIF1gamma antibodies, these two patients were among the patients in remission at follow up.
Conclusions Anti-TIF1gamma antibodies can be detected before clinical symptoms of cancer and may thus become a helpful marker to alert for cancer in patients with myositis. The levels of anti-TIF1gamma antibodies seem to be a prognostic marker for survival in CAM. In addition the TIF1gamma antibodies may persist after cancer treatment even in patients without clinical signs of a persisting malignancy. The clinical relevance of this observation will need to be investigated in larger cohorts with longer observation time.
Disclosure of Interest None Declared
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