目的

        ：先前的研究已经证实抗RNA聚合酶III抗体(anti-RNAP III)阳性和抗着丝点抗体(anti-CENP)、抗拓扑异构酶I抗体(anti-topo I)及anti-RNAP III均阴性的患者增加了发生肿瘤相关性硬皮病的风险。近期的一项研究报道的16例三种抗体全阴性的硬皮病同时合并肿瘤的患者中，有1/4的患者体内存在抗RNPC-3抗体。本研究旨在评估抗RNPC-3抗体与肿瘤之间的关系，同时在大样本的硬皮病患者中观察相关的临床表型。

方法：

        检测合并肿瘤的硬皮病患者体内anti-CENP, anti-topo I, anti-RNAP III, 和anti-RNPC-3抗体的水平。比较不同自身抗体组间疾病的临床特点和肿瘤与硬皮病发病之间的间隔。通过逻辑回归方法评估自身抗体状态与肿瘤相关硬皮病之间的关系。

结果

        ：318例硬皮病合并肿瘤的患者中，有70例anti-RNAP III抗体阳性，有54例anti-topo I抗体阳性，有96例anti-CENP抗体阳性。有12例患者存在anti-RNPC-3抗体阳性。anti-RNPC-3抗体阳性的患者肿瘤发生与硬皮病发病间隔更短(平均0.9年)。与anti-CENP抗体阳性的患者相比，anti-RNPC-3和anti-RNAP III抗体阳性的患者在硬皮病发病后的最初2年内发展成肿瘤的风险增高大于4倍。anti-RNPC-3抗体阳性的患者多具有严重的限制性肺疾病、胃肠受累、雷诺现象和肌病。

结论

        ：Anti-RNPC-3抗体与anti-RNAP III抗体类似，与硬皮病发病后肿瘤发生风险增加相关。这些资料提示部分硬皮病患者存在肿瘤诱导的自身免疫性特点。

        END

        附原文：

OBJECTIVE

        :Prior studies have demonstrated an increased risk of cancer-associated scleroderma in patients with anti-RNA polymerase III (anti-RNAP III) autoantibodies as well as in patients who are triple-negative for anticentromere (anti-CENP), anti-topoisomerase I (anti-topo I), and anti-RNAP III (also known as anti-POL) autoantibodies (referred to as CTP negative). In a recent study of 16 CTP-negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC-3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti-RNPC-3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients.

METHODS

        : Scleroderma patients with cancer were assayed for anti-CENP, anti-topo I, anti-RNAP III, and anti-RNPC-3 autoantibodies. Disease characteristics and the cancer-scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer-associated scleroderma was assessed by logistic regression.

RESULTS

        :Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti-RNAP III, 54 (17.0%) were positive for anti-topo I, and 96 (30.2%) were positive for anti-CENP. Twelve patients (3.8% of the overall group or 12.2% of CTP-negative patients) were positive for anti-RNPC-3. Patients with anti-RNPC-3 had a short cancer-scleroderma interval (median 0.9 years). Relative to patients with anti-CENP, patients with anti-RNPC-3 and those with anti-RNAP III had a >4-fold increased risk of cancer within 2 years of scleroderma onset (for anti-RNPC-3-positive patients, odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.10-16.9 [P = 0.037]; for anti-RNAP III-positive patients, OR 4.49, 95% CI 1.98-10.2 [P < 0.001]). Patients with anti-RNPC-3 had severe restrictive lung disease, gastrointestinal disease, Raynaud's phenomenon, and myopathy.

CONCLUSION

        :Anti-RNPC-3 autoantibodies, similar to anti-RNAP III autoantibodies, are associated with an increased risk of cancer at the onset of scleroderma. These data suggest the possibility of cancer-induced autoimmunity in this subset of patients with scleroderma.

        引自：Shah AA, Xu G, Rosen A, Hummers LK, Wigley FM, Elledge SJ, Casciola-Rosen L.Brief Report: Anti-RNPC-3 Antibodies As a Marker of Cancer-Associated Scleroderma. Arthritis Rheumatol. 2017 Jun;69(6):1306-1312. doi: 10.1002/art.40065.