Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 15 September 2006, Vol. 108, No. 6, pp. 1965-1971.
Prepublished online as a Blood First Edition Paper on June 6, 2006; DOI 10.1182/blood-2006-01-010124.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
blood-2006-01-010124v1
108/6/1965    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Teachey, D. T.
Right arrow Articles by Grupp, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Teachey, D. T.
Right arrow Articles by Grupp, S. A.
Related Collections
Right arrow Immunobiology
Right arrow Neoplasia
Right arrow Signal Transduction
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

IMMUNOBIOLOGY

Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS)

David T. Teachey, Dana A. Obzut, Kelly Axsom, John K. Choi, Kelly C. Goldsmith, Junior Hall, Jessica Hulitt, Catherine S. Manno, John M. Maris, Nicholas Rhodin, Kathleen E. Sullivan, Valerie I. Brown, and Stephan A. Grupp

From the Divisions of Oncology, Hematology, and Immunology in the Department of Pediatrics, and the Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine.

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by defective Fas-mediated apoptosis, leading to lymphadenopathy, hepatosplenomegaly, and an increased number of double-negative T cells (DNTs). Treatment options for patients with ALPS are limited. Rapamycin has been shown to induce apoptosis in normal and malignant lymphocytes. Since ALPS is caused by defective lymphocyte apoptosis, we hypothesized that rapamycin would be effective in treating ALPS. We tested this hypothesis using rapamycin in murine models of ALPS. We followed treatment response with serial assessment of DNTs by flow cytometry in blood and lymphoid tissue, by serial monitoring of lymph node and spleen size with ultrasonography, and by enzyme-linked immunosorbent assay (ELISA) for anti–double-stranded DNA (dsDNA) antibodies. Three-dimensional ultrasound measurements in the mice correlated to actual tissue measurements at death (r = .9648). We found a dramatic and statistically significant decrease in DNTs, lymphadenopathy, splenomegaly, and autoantibodies after only 4 weeks when comparing rapamycin-treated mice with controls. Rapamycin induced apoptosis through the intrinsic mitochondrial pathway. We compared rapamycin to mycophenolate mofetil, a second-line agent used to treat ALPS, and found rapamycin's control of lymphoproliferation was superior. We conclude that rapamycin is an effective treatment for murine ALPS and should be explored as treatment for affected humans.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
A. Bristeau-Leprince, V. Mateo, A. Lim, A. Magerus-Chatinet, E. Solary, A. Fischer, F. Rieux-Laucat, and M.-L. Gougeon
Human TCR {alpha}/{beta}+ CD4-CD8- Double-Negative T Cells in Patients with Autoimmune Lymphoproliferative Syndrome Express Restricted V{beta} TCR Diversity and Are Clonally Related to CD8+ T Cells
J. Immunol., July 1, 2008; 181(1): 440 - 448.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. T. Teachey, A. E. Seif, V. I. Brown, M. Bruno, R. M. Bunte, Y. J. Chang, J. K. Choi, J. D. Fish, J. Hall, G. S. Reid, et al.
Targeting Notch signaling in autoimmune and lymphoproliferative disease
Blood, January 15, 2008; 111(2): 705 - 714.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Mariotti, J. Foley, U. Jung, T. Borenstein, N. Kantardzic, S. Han, J. T. Hanson, E. Wong, N. Buxhoeveden, J. B. Trepel, et al.
Ex Vivo Rapamycin Generates Apoptosis-Resistant Donor Th2 Cells That Persist In Vivo and Prevent Hemopoietic Stem Cell Graft Rejection
J. Immunol., January 1, 2008; 180(1): 89 - 105.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020