CHARACTERIZATION OF THE PATHOGENESIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM)

淋巴管平滑肌瘤病 (LAM) 发病机制的特征

• 批准号: 6162716
• 负责人: J MOSS
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162716
• 关键词: antigen antibody reaction; ascites; cellular pathology; clinical research; dyspneas; glycoproteins; histopathology; human subject; immunocytochemistry; immunoelectron microscopy; leiomyoma; lung; monoclonal antibody; northern blottings; oncoproteins; pneumothorax disorder; respiratory reflex; smooth muscle

Lymphangioleiomyomatosis (LAM) is a rare disease that occurs primarily in women of reproductive age. Clinical manifestations include spontaneous pneumothorax, slowly progressive dyspnea, chylothorax, hemoptysis, and chylous ascites. The cardinal pathologic finding is a proliferation of immature-appearing, disorganized smooth muscle cells (LAM cells) in the lung and axial lymphatics. LAM cells react with monoclonal antibody HMB45 which recognizes melanocyte lineage-specific antigen(s). We report herein the comprehensive evaluation of 35 patients with LAM (age 42.3 +/- 8.6 yr). Most patients had exertional dyspnea (83%) and pneumothorax (69%). Most common abnormalities on pulmonary function tests were decreased DLco (83%), hypoxemia (57%), and airway obstruction (51%). By computed tomography, numerous thin-walled cysts throughout both lungs were found in all patients. Most patients (97%) had abnormal ventilation and/or perfusion lung scans. An unusual "speckling" pattern was observed on ventilation scans of 74% of patients. Common extrapulmonary features were renal angiomyolipoma (60%) and retroperitoneal adenopathy (77%). Bronchoalveolar lavage was performed in 16 patients and found to be safe. Percentage of LAM cells reactive with HMB45 was variable (17-67%) in lung biopsy specimens from 10 patients. Despite hormonal manipulation, the lung function of most patients continued to decline. More effective therapy will require a better understanding of the pathogenesis of LAM at the molecular and cellular level.

淋巴管平滑肌瘤病 (LAM) 是一种罕见疾病，主要发生在 在育龄妇女中。临床表现包括 自发性气胸、缓慢进行性呼吸困难、乳糜胸、 咯血、乳糜性腹水。主要的病理发现是 看起来不成熟、紊乱的平滑肌细胞的增殖 （LAM 细胞）位于肺和轴向淋巴管中。 LAM 细胞反应 识别黑色素细胞谱系特异性的单克隆抗体 HMB45 抗原。现报告35例患者的综合评价 与 LAM（年龄 42.3 +/- 8.6 岁）。大多数患者有劳力性呼吸困难 (83%) 和气胸 (69%)。最常见的肺部异常 功能测试显示 DLco 下降（83%）、低氧血症（57%）和气道下降 阻塞（51%）。通过计算机断层扫描，发现许多薄壁囊肿 所有患者的双肺均发现了这种情况。大多数患者（97%） 肺通气和/或灌注扫描异常。一个不寻常的 74% 的通气扫描中观察到“斑点”模式 患者。常见的肺外特征是肾血管平滑肌脂肪瘤（60%） 和腹膜后淋巴结肿大（77%）。支气管肺泡灌洗是 对 16 名患者进行了实验，结果显示是安全的。 LAM细胞的百分比 肺活检标本中与 HMB45 的反应是可变的 (17-67%) 10名患者。尽管进行了激素调控，大多数人的肺功能 患者数量持续下降。更有效的治疗需要 更好地了解 LAM 的分子和发病机制 细胞水平。