Comment on: Favourable complete remission of anti-OJ antibody-positive myositis after lung cancer resection
Comment on: Favourable complete remission of anti-OJ antibody-positive myositis after lung cancer resection
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点评：肺癌切除后抗OJ抗体阳性肌炎完全缓解
DOI：
10.1093/rheumatology/keac170
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发表时间：
2022
期刊：
影响因子：
3.9
通讯作者：
Akiyama M.
中科院分区：
文献类型：
--
作者：
Muro Y;Nishida K;Yamashita Y;Koizumi H;Takeichi T;Satoh M;Akiyama M.
亲爱的编辑，我们饶有兴趣地阅读了柴田博士等人的文章。[1]报道了一个病例，其中肺癌切除术在没有免疫抑制治疗的情况下改善了抗OJ抗体阳性肌炎。这些作者还表明，抗OJ抗体（Abs）在癌症切除术后消失，并表明肌炎，癌症和自身抗体（autoAb）状态之间可能存在关系。众所周知，抗TIF 1-c Ab是癌症相关DM的血清学标志物[2]。癌细胞中TIF 1-c的异常表达可能刺激与肌肉和皮肤中的抗原交叉反应的自身抗体的产生。尽管柴田博士等人的报告没有说明癌症中OJ抗原的新抗原形成，但抗OJ抗体可能与抗肿瘤反应和肌炎有关。抗OJ抗体识别含有9种合成酶和3种非催化组分的多酶合成酶复合物[3]。有趣的是，许多氨酰tRNA合成酶（ARS）的突变，包括几种合成酶和OJ抗原的组分，已在各种癌症中报道[4]。由于线/点印迹免疫测定法通常不能检测抗OJ免疫沉淀阳性血清中的抗OJ Ab [5]，我们旨在建立用于测量抗OJ Ab的ELISA。我们最近发现重组赖氨酰tRNA合成酶与抗OJ抗体具有高度反应性;这是除了异亮氨酰-tRNA合成酶的反应性之外，异亮氨酰-tRNA合成酶已被认为是主要的靶向自身抗原[3]。我们的ELISA表现良好，与免疫沉淀结果几乎完全一致。在13例抗OJ Ab阳性患者中，我们发现4例患者有癌症病史。抗OJ抗体和癌症发展之间是否存在真正的关联尚不清楚。我们提出了一项荟萃分析，以评估抗OJ抗体和癌症发展之间的关联，通过比较抗OJ阳性患者与抗OJ阴性抗ARS阳性患者的癌症发病率和癌症死亡率。本研究经名古屋大学医院伦理委员会批准后进行。我们在PubMed中检索了截至2022年2月以英文发表的原始文章。检索词为“抗OJ”或"抗异亮氨酸“或”抗ARS“或”抗合成酶综合征“。排除的文章包括综述、社论、病例报告、重叠数据和使用线/点印迹法检测抗OJ抗体的研究。只有3项研究使用RNA和/或蛋白质免疫沉淀进行抗OJ Ab检测，并阐明了抗OJ阳性患者和抗OJ非ARS阳性患者的癌症发病率和/或癌症死亡率[6-8]。由于在我们之前的研究中没有提到抗非OJ ARS阳性患者的癌症发病率和癌症死亡率数据[3]，我们调查了这些患者的医疗记录。在我们的队列中，13名抗OJ阳性患者中有4名有癌症史，其中1名死于癌症，而42名抗非OJ ARS-Abs患者中有3名有癌症史，没有死于癌症。Hamaguchi等人报告了8例抗OJ阳性患者中有2例有癌症/恶性肿瘤病史，这2例患者均存活[6]。Aggarwal et al.提到，五分之二的抗OJ阳性患者死于癌症，尽管他们没有提到抗非OJ ARS阳性患者中的癌症患者数量[7]。此外，另一项日本神经病学队列研究显示，14例抗OJ抗体患者中有3例患有癌症，尽管他们没有提及患者预后[8]。本荟萃分析纳入了4项研究（473例患者）。抗OJ阳性患者40例，抗非OJ ARS阳性患者40例。
DEAR EDITOR, We read with interest the article by Dr Shibata et al.[1] that reported a case in which lung cancer resection ameliorated anti-OJ antibody-positive myositis without immunosuppressive therapy. Those authors also showed that anti-OJ antibodies (Abs) disappeared after cancer resection and suggested a possible relationship between myositis, cancer and autoantibody (autoAb) status. Anti-TIF1-c Abs are well known to be a serological marker of cancer-associated DM [2]. The aberrant expression of TIF1-c in cancer cells may stimulate the production of autoAbs that cross-react with antigens in muscle and skin. Although the report by Dr Shibata et al. did not address the neo-antigen formation of OJ antigens in cancer, anti-OJ Abs might be linked to the anti-tumor response and to myositis. Anti-OJ Abs recognize a multi-enzyme synthetase complex that contains nine synthetases and three noncatalytic components [3]. Interestingly, mutations of many aminoacyl tRNA synthetases (ARSs), including several synthetases and components of OJ antigens, have been reported in various cancers [4]. Because line/dot blot immunoassays often fail to detect anti-OJ Abs in anti-OJ immunoprecipitation-positive sera [5], we aimed to establish an ELISA for measuring anti-OJ Abs. We recently showed recombinant lysyltRNA synthetase to be highly reactive with anti-OJ Abs; this was in addition to the reactivity of isoleucyl-tRNA synthetase, which has been recognized as a major target autoantigen [3]. Our ELISAs performed well, agreeing almost perfectly with the immunoprecipitation results. We found four patients with a history of cancer among 13 anti-OJ Ab-positive patients. Whether a true association between anti-OJ Abs and cancer development exists is unknown. We present a meta-analysis to assess the association between anti-OJ Abs and cancer development by comparing anti-OJ-positive patients to anti-OJ-negative anti-ARS-positive patients in terms of cancer incidence and cancer mortality. This study was conducted with the approval of the ethics committee of Nagoya University Hospital. We searched PubMed for original articles published in English up to February 2022. The search term was ‘anti-OJ’OR ‘anti-isoleucyl’OR ‘anti-ARS’OR ‘antisynthetase syndrome’. Excluded articles were reviews, editorials, case reports, overlapping data and studies using line/dot blots for detecting anti-OJ Abs. Only three studies usedRNA and/or protein immunoprecipitation for anti-OJ Ab detection and clarified cancer incidence and/or cancer mortality both in anti-OJ-positive patients and in antinon-OJ ARS-positive patients [6–8]. Because data on cancer incidence and cancer mortality in anti-non-OJ ARS-positive patients had not been mentioned in our previous study [3], we surveyed the medical records of these patients. In our cohort, four of the 13 anti-OJ-positive patients had a history of cancer and one of them died of cancer, whereas three of the 42 patients with anti-non-OJ ARS-Abs had a history of cancer and none died of cancer. Hamaguchi et al. reported a history of cancer/malignancy in two out of eight anti-OJ-positive patients, both of whom were alive [6]. Aggarwal et al. mentioned that two out of five anti-OJ-positive patients died from cancer, although they did not mention the number of patients with cancer in anti-non-OJ ARS-positive patients [7]. In addition, another Japanese neurology cohort study showed that three out of 14 patients with anti-OJ Abs had cancer, although they did not mention patient prognosis [8]. Four studies (473 patients) were included in the present meta-analysis. Anti-OJ-positive patients numbered 40 while anti-non-OJ ARS-positive …