Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies
Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies
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抗转录因子 Sp4 共存自身抗体与具有抗 TIF1γ 自身抗体的皮肌炎患者的癌症风险降低相关
DOI：
10.1136/ard-2022-222441
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发表时间：
2022
影响因子：
27.4
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Hosono Yuji;Sie Brandon;Pinal-Fernandez Iago;et al.
目的：在皮肌炎（DM）中，自身抗体与独特的临床表型相关。例如，抗tif1γ自身抗体与癌症风险增加有关。本研究的目的是发现新的糖尿病自身抗体。方法对43例糖尿病患者血清进行免疫沉淀测序，发现转录因子Sp4是一种新的自身抗原；通过显示患者血清免疫沉淀全长Sp4蛋白证实了这一点。采用ELISA对371例约翰霍普金斯大学肌炎患者（DM 255例，抗合成酶综合征28例，免疫介导的坏死性肌病40例，包涵体肌炎29例，多发性肌炎19例）、80例风湿病对照（干燥综合征25例，系统性红斑狼疮25例，类风湿性关节炎30例）和200例健康对照者的血清进行抗sp4自身抗体的筛选。来自匹兹堡大学的46例抗tif1 γ阳性患者血清的验证队列也筛选了抗sp4自身抗体。结果DM患者27例（10.5%）、RA患者1例（3.3%）存在抗sp4自身抗体，其他临床组无。在DM患者中，抗tif1γ自身抗体中检测到96.3%的抗sp4自身抗体。26例抗sp4自身抗体tif1 γ阳性患者中无肿瘤发生（0%）。而在35例tif1 γ阳性且无抗sp4自身抗体的患者中，有5例（14%,p=0.04）发生肿瘤。在验证队列中，在15例具有抗sp4自身抗体的tif1 γ阳性患者中，2例（13.3%）发生癌症。31例无抗sp4自身抗体的tif1 γ阳性患者中，21例（67.7%,p<0.001）发生肿瘤。结论抗sp4自身抗体可识别抗tif1 γ阳性DM患者的低癌风险亚组。
ObjectivesIn dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies.MethodsPhage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren’s syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies.ResultsAnti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer.ConclusionsAnti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.
DOI：
10.1164/rccm.201308-1483st
发表时间：
2013-09-15
影响因子：
24.7
作者：
Travis, William D.;Costabel, Ulrich;Valeyre, Dominique
通讯作者：
Valeyre, Dominique