Myositis-specific autoantibodies and their association with malignancy in Italian patients with polymyositis and dermatomyositis

Myositis-specific autoantibodies and their association with malignancy in Italian patients with polymyositis and dermatomyositis
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DOI:
10.1007/s10067-016-3453-0
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发表时间:
2017-02-01
影响因子:
3.4
通讯作者:
Selmi, Carlo
Selmi, Carlo
中科院分区:
医学3区
文献类型:
--
作者:
Ceribelli, Angela;Isailovic, Natasa;Selmi, Carlo

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本研究旨在明确特发性炎性肌病患者队列中肌炎特异性抗体的特征,并确定其与癌症的相关性。通过蛋白质和RNA免疫沉淀法检测40例多发性肌炎、皮肌炎患者和对照组的血清以检测自身抗体,并使用免疫沉淀-Western印迹法进行抗MJ/NXP-2、抗MDA 5和抗TIF 1 γ/α鉴定。重新评估了医疗记录,特别关注癌症。抗MJ/NXP-2和抗TIF 1 γ/α是皮肌炎中最常见的抗体。在6例皮肌炎病例中,我们发现5例实体癌和1例霍奇金淋巴瘤长期缓解。在癌症相关皮肌炎患者中,3例抗TIF 1 γ/α阳性,2例抗Mi-2阳性,1例抗MJ/NXP-2阳性。抗TIF 1 γ的最强阳性见于两种活动性癌症,在无癌症或7年缓解期霍奇金淋巴瘤中,该抗体为阴性或低滴度阳性。20例多发性肌炎患者中有4例(20%)患有实体癌,但未发现与自身抗体的特异性相关性;此外,4例抗合成酶综合征病例中无一例有癌症病史。在对照血清中未观察到血清肌炎相关自身抗体,导致抗TIF 1 γ/α(+)患者中副肿瘤性DM风险的阳性预测值75%,阴性预测值78.5%,灵敏度50%,特异性92%,ROC曲线下面积0.7083。肌炎特异性自身抗体可以通过免疫沉淀的使用来识别,并且它们与癌症的关联对于皮肌炎中的抗TIF 1 γ/α特别清楚。这种关联应在临床实践中通过免疫沉淀的前瞻性研究进行评估。
This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1 gamma/alpha identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1 gamma/alpha were the most common antibodies in dermatomyositis. In six dermatomyositis cases, we found five solid forms of cancer and one Hodgkin's lymphoma in long-term remission. Among patients with cancer-associated dermatomyositis, three were positive for anti-TIF1 gamma/alpha, two for anti-Mi-2, and one for anti-MJ/NXP-2. The strongest positivity of anti-TIF1 gamma was seen in two active forms of cancer, and this antibody was either negative or positive at low titers in the absence of cancer or in the 7-year remission Hodgkin's lymphoma. Four out of twenty (20 %) patients with polymyositis had solid cancer, but no specific association with autoantibodies was identified; further, none of the four cases of antisynthetase syndrome had a history of cancer. No serum myositis-associated autoantibody was observed in control sera, resulting in positive predictive value 75 %, negative predictive value 78.5 %, sensitivity 50 %, specificity 92 %, and area under the ROC curve 0.7083 for the risk of paraneoplastic DM in anti-TIF1 gamma/alpha (+) patients. Myositis-specific autoantibodies can be identified thanks to the use of immunoprecipitation, and their association with cancer is particularly clear for anti-TIF1 gamma/alpha in dermatomyositis. This association should be evaluated in a prospective study by immunoprecipitation in clinical practice.