Tian Xinlun, Glass Jennifer E, Kwiatkowski David J, Towbin Alexander J, Li Yinan, Sund Kristen L, Krueger Darcy A, Franz David N, McCormack Francis X, Gupta Nishant
Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.
Division of Human Genetics.
Ann Am Thorac Soc. 2021 May;18(5):815-819. doi: 10.1513/AnnalsATS.202008-911OC.
Lymphangioleiomyomatosis (LAM) is a female-predominant lung disease caused by mutations in the tuberous sclerosis complex (TSC) genes and . To examine the association between TSC mutation subtypes and the prevalence of LAM in women with TSC. Adult women seen at the Cincinnati Children's Hospital Medical Center's TSC clinic were stratified into the following three groups: those with mutation, those with mutation, and those with no mutation identified (NMI). Individual TSC manifestations were ascertained by blinded review of chest computed tomographic scans (LAM, multifocal micronodular pneumocyte hyperplasia, and sclerotic bone lesions) and chart review (all other manifestations). The association between mutation status and TSC manifestations was assessed by the Wilcoxon rank-sum test. Our cohort consisted of 55 TSC women, including 30/55 (55%) with , 12/55 (22%) with , and 13/55 (23%) with NMI. Twenty-three women (42%) had characteristic cysts consistent with LAM, of whom 16 had mutations and seven had NMI. The prevalence of LAM was higher in women with mutations compared with women with mutations (16/29 [55%] vs. 0/12; = 0.003). Similarly, renal angiomyolipomas were more common in women with mutations compared with women with mutations (29/30 [97%] vs. 6/12 [50%]; = 0.01). There was no association between TSC mutation subtype and the presence of multifocal micronodular pneumocyte hyperplasia, sclerotic bone lesions, and skin or brain involvement. Serum VEGF-D (vascular endothelial growth factor-D) concentrations (median [95% confidence interval]) tended to be higher in patients harboring mutations compared with patients with mutations (725 pg/ml [612-1,317] vs. 331 pg/ml [284-406]; = 0.03) and in patients with LAM compared with patients without LAM (725 pg/ml [563-1,609] vs. 429 pg/ml [357-773]; = 0.02). LAM and angiomyolipomas are more common in women with TSC harboring mutations compared with women with mutations. Serum VEGF-D is a useful biomarker to suggest the presence of LAM in women with TSC.
淋巴管平滑肌瘤病（LAM）是一种女性为主的肺部疾病，由结节性硬化复合物（TSC）基因 和 的突变引起。为了研究TSC突变亚型与患有TSC的女性中LAM患病率之间的关联。在辛辛那提儿童医院医疗中心TSC诊所就诊的成年女性被分为以下三组：有 突变的女性、有 突变的女性以及未发现突变（NMI）的女性。通过对胸部计算机断层扫描（LAM、多灶性微小结节性肺细胞增生和硬化性骨病变）进行盲法评估以及查阅病历（所有其他表现）来确定个体TSC表现。通过Wilcoxon秩和检验评估突变状态与TSC表现之间的关联。我们的队列包括55名患有TSC的女性，其中30/55（55%）有 突变，12/55（22%）有 突变，13/55（23%）为NMI。23名女性（42%）有符合LAM的特征性囊肿，其中16名有 突变，7名有NMI。与有 突变的女性相比，有 突变的女性中LAM的患病率更高（16/29 [55%] 对 0/12； = 0.003）。同样，与有 突变的女性相比，有 突变的女性中肾血管平滑肌脂肪瘤更常见（29/30 [97%] 对 6/12 [50%]； = 0.01）。TSC突变亚型与多灶性微小结节性肺细胞增生、硬化性骨病变以及皮肤或脑部受累之间无关联。与有 突变的患者相比，携带 突变的患者血清血管内皮生长因子-D（VEGF-D）浓度（中位数[95%置信区间]）往往更高（725 pg/ml [612 - 1317] 对 331 pg/ml [284 - 406]； = 0.03），与无LAM的患者相比，患有LAM的患者血清VEGF-D浓度更高（725 pg/ml [563 - 1609] 对 429 pg/ml [357 - 773]； = 0.02）。与有 突变的女性相比，患有TSC且携带 突变的女性中LAM和血管平滑肌脂肪瘤更常见。血清VEGF-D是提示患有TSC的女性中存在LAM的有用生物标志物。
