抽象的
Five cases with telomerase reverse transcriptase mutation and pleuroparenchymal fibroelastosishttp://ow.ly/u33930aaral
致编辑:
We read with great interest the article by Newton等。[[1]。他们发现端粒维护机械基因中的突变(端粒酶逆转录酶(Tert), telomerase RNA component (terc),端粒伸长解旋酶1和poly(a)特异性核糖核酸酶)导致可变的间质性肺疾病(ILD)表型,这些表型是普遍进行的[1]。We were particularly interested by the evidence for the first time in the literature of a telomere-related gene mutation associated with pleuroparenchymal fibroelastosis (PPFE). PPFE represented eight out of the 77 (10.4%) cases with genetic aberrations, which is intriguing compared with the rarity of disease among ILDs. Indeed, a possible familial propensity for the development of PPFE was originally suggested by our earlier report of three affected sisters [2]。一个ccording to other published studies, a family history of ILD is observed in 17–57% of PPFE patients [3-5]。
同样,从2006年到2015年,将12例诊断为PPFE的患者被转介给我们部门以寻求进一步的建议;其中有10个被调查Tertandterc突变。Tertmutations were identified in five (50%) cases (表格1)。noticeably, a patient with a history of “pulmonary fibrosis” in his sister, chronic liver disease and unexplained cardiomyopathy, was negative forTertandterc但未测试过端粒伸长酶1和poly(a)特异性核糖核酸酶的调节剂。如本文所述,我们的研究包括一群女性(五分之四)(41-63岁)。三名患者具有ILD的家族背景,所有患者的体重指数低(平均18.8 kg·M-2),肺炎或肺炎的四例发生。ILD和PPFE诊断之间的延迟很长,范围为14-45个月。在所有情况下,高分辨率计算机断层扫描(HRCT)都是PPFE的典型特征,并且在四名患者(三名手术肺活检(SLB),一只肺epplant)中得到病理证实。我们的患者患有迅速进行性纤维化,一氧化碳肺部肺部的扩散能力平均下降为每年6.1%,强迫生命力(FVC)每年下降3.7%。随访结束时,两名患者被移植而没有重大血液学并发症,一名患者在进行胸膜炎和SLB的视频辅助胸腔镜检查后屈服于急性加重。一名未经治疗的患者表现良好,另一位患者在吡富烯酮下继续进展。关于非突变患者,一名被移植,两名具有稳定的肺功能,两名死于末端呼吸衰竭。FVC平均每年下降的平均年龄没有差异(突变患者为-3.7%相对未突出的-2.6%;p = 0.4)。
我们的数据与n的数据一致ewton等。[[1] and suggest the importance of searching telomere-related gene mutations in patients with PPFE even without a family history of ILD. These findings also raise pathogenic questions.
Interestingly, two patients presented Sjögren's syndrome. Autoimmune features have already been described in PPFE [4]。Data indicate that both telomerase activity and telomerase length are modified in various systemic immune-mediated diseases, including Sjögren's syndrome [8,,,,9]。炎症引起的免疫细胞中加速的端粒侵蚀可能导致过早的细胞衰老和凋亡增加,导致免疫系统无法控制[8]。可能假设端粒酶突变可能有利于Sjögren综合征等自身免疫性疾病。
尽管胸膜充质的变化是PPFE的典型变化,而上叶具有明显的偏见,但值得注意的是,我们的四名患者在HRCT下的下部地区也表现出较小的间质性纤维化,其病理模式最让人联想到通常的间质性肺炎(UIP)(UIP)(UIP)在SLB的下部,三名患者。在一项针对12名PPFE患者的研究中涡流等。[[4],所有七个具有多个活检的病例均显示出在下叶中的病理参与模式,在HRCT时注意到,在三例中与UIP相对应。同样,在O的研究中da等。[[10],在组织学上,有11名符合PPFE诊断的放射学标准的患者中有9名被确认为具有UIP的PPFE,其中包括三名具有ILD家族史的患者。但是,我们的患者和先前报道的患者表现出了与特发性肺纤维化明显不同的疾病表现。
现在还不清楚弹性组织变性和铁道部e common collagen fibroproliferation are distinctive pathways of chronic scarring, and whether they may reflect discrete responses to primarily different lung damages or in differently susceptible subjects. A Brazilian group has demonstrated that elastic deposition accompanies collagen deposition in the major forms of acute and chronic idiopathic interstitial pneumonias [11]。Hirota等。[[12]已经分析了四名PPFE患者的连续肺活检,并提出先前的间质性炎症或急性肺损伤可能是Primum移动of disease. Enomoto等。[[13]表明,低于PPFE和UIP中的上叶的弹性纤维量显着降低。此外,米iele等。[[14] described a spontaneous pulmonary fibrosis in aged donkeys that shared similarities with human PPFE with a localised fibrosis in the uppermost and dorsal zones. In addition, PPFE features overlap with those of apical caps, the prevalence of which increases in the elderly and may be related to microscopic tears in tissue substructure caused by the weight of the lung itself [15]。
综上所述,这些数据表明,在暴露于肺损伤的情况下,细胞外基质会通过重塑其所有成分做出反应。与端粒相关基因突变的患者可能会倾向于对周围肺的术语损伤[16]。在细胞外基质重塑过程中,上下叶之间的弹性反应和胶原蛋白纤维蛋白蛋白质量的差异程度可能是由于肺部区域受到不同的机械菌株的影响,并且PPFE和一致性或随后发展或随后发展在基地中uip。
脚注
利益冲突:没有声明。
- 已收到October 15, 2016.
- 公认2017年2月19日。
- 版权所有©ERS 2017