Anti-synthetase syndrome: a new autoantibody to phenylalanyl transfer RNA synthetase (anti-Zo) associated with polymyositis and interstitial pneumonia
Anti-synthetase syndrome: a new autoantibody to phenylalanyl transfer RNA synthetase (anti-Zo) associated with polymyositis and interstitial pneumonia
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DOI：
10.1093/rheumatology/kem045
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发表时间：
2007-06-01
期刊：
影响因子：
5.5
通讯作者：
McHugh, N.
中科院分区：
文献类型：
--
作者：
Betteridge, Z.;Gunawardena, H.;McHugh, N.
Objective.针对氨酰tRNA合成酶的自身抗体与肌炎、关节炎、雷诺现象、机械手、发热和间质性肺炎相关，临床上称为抗合成酶综合征（ASS）。本研究的目的是表征的自身抗体谱在ASS的临床特征的患者，其常规诊断测试是阴性的先前确定的抗合成酶自身抗体。采用间接免疫荧光、免疫扩散、ELISA和免疫印迹等常规方法，对1例间质性肺炎伴近端肌病、雷诺现象和关节炎患者的血清进行自身抗原特异性分析。用RNA和蛋白质免疫沉淀法进一步分析自身抗体的特异性。结合免疫沉淀、SDS-PAGE和MALDI-TOF质谱，对免疫沉淀中发现的新的自身抗原进行了进一步的蛋白质组学鉴定。通过ELISA和免疫扩散法对患者血清进行的诊断测试为阴性。Hep-2细胞的间接免疫荧光结果为ANA阴性，但可见较强的胞浆斑点。患者血清的免疫印迹显示约60 kDa的未知阳性条带。蛋白质免疫沉淀揭示了两种蛋白质的分子量约为60和70 kDa的存在下，和RNA免疫沉淀揭示了对应于tRNA合成酶的条带的存在下。结合免疫沉淀和质谱分析，新的免疫沉淀靶点被鉴定为苯丙氨酰tRNA合成酶α和β链。我们报告以前未表征的自身抗体苯丙氨酰tRNA合成酶，题为抗ZO的鉴定。这是抗合成酶综合征患者中的第八种抗合成酶自身抗体。
Objective. Autoantibodies directed against the aminoacyl tRNA synthetases are associated with myositis, arthritis, Raynaud's phenomenon, mechanic's hands, fever and interstitial pneumonia, clinically referred to as the anti-synthetase syndrome (ASS). The aim of this study was to characterize the autoantibody profile in a patient with clinical features of ASS whose routine diagnostic testing was negative for the previously identified anti-synthetase autoantibodies.Methods. Serum from a patient presenting with interstitial pneumonia followed by proximal myopathy, Raynaud's phenomenon and arthrlagia was analysed for autoantigen specificity by routine methods including indirect immunofluorescence, immunodiffusion, ELISA and immunoblotting. The autoantibody specificity was further analysed by RNA and protein immunoprecipitation. Novel autoantigens found on protein immunoprecipitation were further characterized using a proteomic approach, combining immunoprecipitation, SDS-PAGE and MALDI-TOF mass spectrometry.Results. Diagnostic testing on the patient's serum was negative by ELISA and immunodiffusion. Indirect immunofluorescence using Hep-2 cells was ANA negative, although a strong cytoplasmic speckle was seen. Immunoblotting with the patient serum displayed an unknown positive band at approximately 60 kDa. Protein immunoprecipitation revealed the presence of two proteins with molecular weights of approximately 60 and 70 kDa, and RNA immunoprecipitation revealed the presence of a band corresponding to a tRNA synthetase. Using a combination of immunoprecipitation and mass spectrometry, the novel immunoprecipitation targets were identified as phenylalanyl tRNA synthetase alpha and beta chains.Conclusions. We report the identification of previously uncharacterized autoantibodies to phenylalanyl tRNA synthetase, entitled anti-Zo. This is the eighth anti-synthetase autoantibody in a patient with anti-synthetase syndrome.