Antibody alpha PEP13h Reacts With Lymphangioleiomyomatosis Cells in Lung Nodules

作者：Valencia Julio C; Steagall Wendy K; Zhang Yi; Fetsch Patricia; Abati Andrea; Tsukada Katsuya; Billings Eric; Hearing Vincent J; Yu Zu Xi; Pacheco Rodriguez Gustavo; Moss Joel^*

来源：Chest, 2015, 147(3): 771-777.

DOI：10.1378/chest.14-0380

BACKGROUND: Lymphangioleiomyomatosis (LAM) is characterized by the proliferation in the lung, axial lymphatics (eg, lymphangioleiomyomas), and kidney (eg, angiomyolipomas) of abnormal smooth muscle-like LAM cells, which express melanoma antigens such as Pmel17/gp100 and have dysfunctional tumor suppressor tuberous sclerosis complex (TSC) genes TSC2 or TSC1. Histopathologic diagnosis of LAM in lung specimens is based on identification of the Pmel17 protein with the monoclonal antibody HMB-45.
METHODS: We compared the sensitivity of HMB-45 to that of antipeptide antibody alpha PEP13h, which reacts with a C-terminal peptide of Pmel17. LAM lung nodules were laser-capture microdissected to identify proteins by Western blotting.
RESULTS: HMB-45 recognized approximately 25% of LAM cells within the LAM lung nodules, whereas alpha PEP13h identified > 82% of LAM cells within these structures in approximately 90% of patients. Whereas HMB-45 reacted with epithelioid but not with spindle-shaped LAM cells, alpha PEP13h identified both spindle-shaped and epithelioid LAM cells, providing greater sensitivity for detection of all types of LAM cells. HMB-45 recognized Pmel17 in premelanosomal organelles; alpha PEP13h recognized proteins in the cytoplasm as well as in premelanosomal organelles. Both antibodies recognized a Pmel17 variant of approximately 50 kDa.
CONCLUSIONS: Based on its sensitivity and specificity, alpha PEP13h may be useful in the diagnosis of LAM and more sensitive than HMB-45.

• 出版日期2015-3
• 单位NIH