A new autoantibody to valyl transfer RNA synthetase associated with anti-synthetase syndrome
Tsuneo Sasai, Ran Nakashima, Mirei Shirakashi, Ryosuke Hiwa, Hideaki Tsuji, Koji Kitagori, Shuji Akizuki, Hajime Yoshifuji, Tsuneyo Mimori, Akio Morinobu
Abstract
Dear Editor, The aminoacyl tRNA synthetase (ARS) antibody is the most frequently detected myositis-specific autoantibody in idiopathic inflammatory myopathy [1]. ARS antibody-positive patients frequently have myositis, as well as interstitial lung disease (ILD), polyarthritis, RP, fever and mechanic’s hands. Together, these symptoms define antisynthetase syndrome (ASSD) [2]. ARS binds amino acids to tRNA in the presence of adenosine triphosphate and catalyses the synthesis of aminoacyl tRNA. In humans, there are 20 different types of ARSs, one for each amino acid. Eight of these tRNA synthetases have been reported as myositis-specific autoantigens [3] [Jo-1 (histidyl), PL-7 (threonyl), PL-12 (alanyl), EJ (glycyl), OJ (isoleucyl), KS (asparaginyl), Zo (phenylalanyl), and Ha (tyrosyl)] and are associated with the ASSD phenotype, with the latter two being the least commonly involved [4, 5]. In this study we identified a new anti-ARS directed against valyl tRNA synthetase (VRS) in a patient with typical features of ASSD. A 43-year-old man was admitted to our hospital with occasional fever, myalgia and arthralgia lasting 2 months. He also reported RP. Physical examination revealed swollen fingers and weakness of the deltoid and quadriceps muscles. Laboratory studies revealed the following: lactate dehydrogenase, 732 U/l; creatine phosphokinase (CK), 2472 U/l; aldolase, 46.4 IU/l; CRP, 1.5 mg/dl; and Krebs von den Lungen-6, 396 U/ml. Fluorescent ANA was also positive (titre 1:640, with a nucleolar and cytoplasmic pattern) but disease-specific autoantibodies were negative. Chest CT revealed ILD, with a pattern classified as a non-specific interstitial pneumonia. Fat-saturated T2-weighted MRI revealed diffuse high-intensity signals in the deltoid and iliopsoas muscles and needle electromyography of these muscles revealed myogenic changes. A muscle biopsy of the left quadriceps femoris showed necrotic muscle fibres and endomysial infiltration of mononuclear cells, consistent with myositis. Based on these findings, the patient was clinically diagnosed with ASSD. CT also revealed a swollen mediastinal lymph node that was pathologically diagnosed as an undifferentiated carcinoma. Immunohistochemical analysis of the lymph node did not identify it as a lymphoma, sarcoma or specific type of carcinoma. 18F-fluorodeoxyglucose PET did not reveal any lesions other than the swollen mediastinal lymph node. Thus the patient was diagnosed with ASSD coexisting with a cancer of unknown origin.