ELISA, protein immunoprecipitation and line blot assays for anti-TIF1-gamma autoantibody detection in cancer-associated dermatomyositis.

OBJECTIVES: Anti-TIF1-gamma autoantibodies can be detected with immunoprecipitation (IP), line blot (LB) and ELISA. We compared assay performance in patients with DM and the potential of these assays to detect anti-TIF1-gamma positive cancer-associated DM (CADM). METHODS: We included sera from 131 patients with DM followed at Karolinska University Hospital, Stockholm, Sweden and 82 healthy controls. Serum samples taken at DM diagnosis were tested for anti-TIF1-gamma autoantibodies with IP, two ELISAs (in-house and commercial) and LB. Cancer diagnosis and dates were obtained from the Swedish national cancer register. CADM was defined as a malignancy that developed within 3 years of DM diagnosis. RESULTS: Anti-TIF1-gamma autoantibodies were detected in 19/101 (18.8%), 15/113 (13.2%), 34/131 (26%) and 45/131 (34.4%) of the patients with IP, LB, in-house and commercial ELISA, respectively. The anti-TIF1-gamma results from the in-house ELISA were confirmed with IP in 93 of 101 (92%) cases, κ = 0.76, with a commercial ELISA in 110 of 131 (84%) cases, κ = 0.63, and with LB in 101 of 113 (89.3%) cases, κ = 0.67. Anti-TIF1-gamma results with IP were confirmed with LB in 85 of 92 (92.4%) cases, κ = 0.73. For detecting CADM, the anti-TIF1-gamma in-house ELISA had a sensitivity of 58% and specificity of 86%, the commercial ELISA had a sensitivity of 63% and specificity of 82%, IP had a sensitivity of 52% and specificity of 92%, LB had a sensitivity of 40% and specificity of 96%. CONCLUSION: The two anti-TIF1-gamma ELISA assays had advantages both for autoantibody detection and to identify anti-TIF1-gamma-positive CADM.

The manifestation of myositis in tick-borne encephalitis as a prophet of severe disease course: a rare case report.

Tick-borne encephalitis (TBE) is one of the most serious neurological tick-transmitted diseases. The initial phase usually occurs with non-specific symptoms such as fever, headache, and muscular pain. The clinical spectrum of the second phase of the disease typically ranges from mild meningitis to severe meningoencephalitis. Our case demonstrates a rare clinical case of acute myositis as manifestation of TBE virus infection. A 33-year-old female was admitted to the Rheumatology centre with a fever followed by proximal muscle pain and weakness. Despite the tick bite history and marginally positive anti-TBE virus IgM titre, the patient did not present any neurological symptoms. Laboratory test results showed elevated creatine kinase (CK) and myoglobin. Other infections, idiopathic inflammatory myopathies, were excluded. TBE virus infection was confirmed by rapid seroconversion of specific IgG class antibodies in serum. The second phase of the disease was followed by neurological symptoms and a repeated increase of CK and myoglobin. We suggest that in the case of acute myositis of unknown cause and the history of thick bite, TBE virus infection should be considered and creatine kinase might be considered as a laboratory marker of disease activity that correlates with the severity of the disease.

Association of Anti-Transcription Intermediary Factor 1γ Antibodies With Paraneoplastic Rheumatic Syndromes Other Than Dermatomyositis.

OBJECTIVE: An association between cancer and dermatomyositis (DM) is well recognized. The high frequency of malignancies detected close to DM diagnosis suggest that DM can be a paraneoplastic syndrome. Recently, anti-transcription intermediary factor 1γ (anti-TIF1γ) has been discovered to be associated with cancer and with DM. A meta-analysis reported the pooled sensitivity of anti-p155 for diagnosing cancer-associated DM to be 78% and the specificity to be 89%. Thus, anti-TIF1γ has shown promising results as a marker for cancer-associated DM. However, none of the studies evaluated the association of anti-TIF1γ with cancer with or without rheumatic diseases other than DM. To clarify the specificity of anti-TIF1γ antibodies as a biomarker for cancer-associated DM, we analyzed the frequency of anti-TIF1γ antibodies in other cancer-associated rheumatic syndromes, as well as in cancer patients and healthy controls. METHODS: Sera from patients with paraneoplastic rheumatic syndrome (n = 91), patients with solid cancer (n = 95), and healthy controls (n = 80) were analyzed for the frequency of anti-TIF1γ IgG by enzyme-linked immunosorbent assay using a commercially available recombinant TIF1γ protein as coating antigen. The cutoff value was calculated by adding 2 SD to the mean optical density value of 80 healthy controls. RESULTS: The rate of anti-TIF1γ IgG positivity was 3.3% (n = 3) in patients with paraneoplastic rheumatic syndrome, 3.1% (n = 3) in cancer patients, and 1.3% (n = 1) in healthy controls. There were no significant differences in positivity between the groups (P < 0.05). CONCLUSION: Anti-TIF1γ antibodies are rarely present in patients with solid cancers or paraneoplastic rheumatic syndromes. This finding strengthens the approach to using anti-TIF1γ IgG as a marker for cancer-associated DM.