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Original Research: Diffuse Lung Disease |

Antibody αPEP13h Reacts With Lymphangioleiomyomatosis Cells in Lung NodulesDetection of Lymphangioleiomyomatosis Cells

Julio C. Valencia, MD; Wendy K. Steagall, PhD; Yi Zhang, PhD; Patricia Fetsch, BS; Andrea Abati, MD; Katsuya Tsukada, MD, PhD; Eric Billings, PhD; Vincent J. Hearing, MD, PhD; Zu-Xi Yu, MD, PhD; Gustavo Pacheco-Rodriguez, PhD; Joel Moss, MD, PhD, FCCP
Author and Funding Information

From the Cardiovascular and Pulmonary Branch (Drs Valencia, Steagall, Zhang, Tsukada, Pacheco-Rodriguez, and Moss), Biochemistry and Biophysics Center (Dr Billings), and Pathology Core (Dr Yu), National Heart, Lung, and Blood Institute, National Institutes of Health; and Pigment Cell Biology Section (Dr Hearing), Laboratory of Cell Biology, and Cytopathology Section (Ms Fetsch and Dr Abati), National Cancer Institute, National Institutes of Health, Bethesda, MD.

CORRESPONDENCE TO: Joel Moss, MD, PhD, FCCP, Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg 10/6D05, 10 Center Dr, MSC-1590, 9000 Rockville Pike, Bethesda, MD 20892-1590; e-mail: mossj@nhlbi.nih.gov


Part of this article has been presented in abstract form (Valencia JC, Steagall WK, Zhang Y, et al. Am J Respir Crit Care Med. 2013;187:A2028).

FUNDING/SUPPORT: The study was supported by the Intramural Research Program, National Institutes of Health; National Heart, Lung, and Blood Institute; and the National Cancer Institute.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(3):771-777. doi:10.1378/chest.14-0380
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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 αPEP13h, 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 αPEP13h 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, αPEP13h 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; αPEP13h 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, αPEP13h may be useful in the diagnosis of LAM and more sensitive than HMB-45.

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