|
|
 Previous Article | Table of Contents | Next Article 
Deficiency of the Fas apoptosis pathway without Fas gene mutations in
pediatric patients with autoimmunity/lymphoproliferation
U Dianzani, M Bragardo, D DiFranco, C Alliaudi, P Scagni, D Buonfiglio, V Redoglia, S Bonissoni, A Correra, I Dianzani and U Ramenghi
Dipartimento di Scienze Mediche, Universita di Torino, Novara, Italy.
Fas (CD95) is a transmembrane molecule that induces programmed cell death
(PCD) of lymphocytes. We examined its function in children with chronic
thrombocytopenia, serum autoantibodies, and lymphadenopathy and/or
splenomegaly. We found that T-cell lines from six of seven patients with
this autoimmune/lymphoproliferative disease (ALD) were relatively resistant
to PCD induced by monoclonal antibodies to Fas. By contrast, Fas function
was normal in control patients with typical chronic idiopathic
thrombocytopenic purpura (ITP) without lymphadenopathy. The defect was not
due to decreased Fas expression, nor to over-production of soluble forms of
Fas. Moreover, it specifically involved the Fas system because PCD was
induced in the normal way by methylprednisolone. Complementary DNA
sequencing of the Fas gene did not identify any causal mutation in patients
with ALD. This distinguished them from patients with the human autoimmune
lymphoproliferative syndrome (ALPS), who carry mutations of the Fas gene.
Moreover, patients with ALD did not show the peripheral expansion of
CD4/CD8 double-negative T cells that characterizes the ALPS phenotype. Fas
signaling involves activation of a sphingomyelinase- catalyzing production
of ceramide. We found that ceramide-induced PCD was defective in patients
with ALD and not in patients with typical chronic ITP. These data suggest
that the ALD patient defect involves the Fas signaling pathway downstream
from the sphingomyelinase and that Fas gene mutations and double-negative
T-cell expansion are not the only signs of a defective Fas system.
Volume 89,
Issue 8,
pp. 2871-2879,
04/15/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
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]
|
|
|
|
|
|
|
R. Clementi, A. Chiocchetti, G. Cappellano, E. Cerutti, M. Ferretti, E. Orilieri, I. Dianzani, M. Ferrarini, M. Bregni, C. Danesino, et al.
Variations of the perforin gene in patients with autoimmunity/lymphoproliferation and defective Fas function
Blood,
November 1, 2006;
108(9):
3079 - 3084.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. T. Teachey, C. S. Manno, K. M. Axsom, T. Andrews, J. K. Choi, B. H. Greenbaum, J. M. McMann, K. E. Sullivan, S. F. Travis, and S. A. Grupp
Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS)
Blood,
March 15, 2005;
105(6):
2443 - 2448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Chiocchetti, M. Indelicato, T. Bensi, R. Mesturini, M. Giordano, S. Sametti, L. Castelli, F. Bottarel, M. C. Mazzarino, L. Garbarini, et al.
High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation
Blood,
February 15, 2004;
103(4):
1376 - 1382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Shin, H. S. Kim, C. S. Kang, W. S. Park, S. Y. Kim, S. N. Lee, J. H. Lee, J. Y. Park, J. J. Jang, C. W. Kim, et al.
Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas
Blood,
May 13, 2002;
99(11):
4094 - 4099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. H. Bleesing, M. R. Brown, S. E. Straus, J. K. Dale, R. M. Siegel, M. Johnson, M. J. Lenardo, J. M. Puck, and T. A. Fleisher
Immunophenotypic profiles in families with autoimmune lymphoproliferative syndrome
Blood,
October 15, 2001;
98(8):
2466 - 2473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Parsons, R. G. Jones, M.-S. Tsao, B. Odermatt, P. S. Ohashi, and J. R. Woodgett
Expression of Active Protein Kinase B in T Cells Perturbs Both T and B Cell Homeostasis and Promotes Inflammation
J. Immunol.,
July 1, 2001;
167(1):
42 - 48.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Straus, E. S. Jaffe, J. M. Puck, J. K. Dale, K. B. Elkon, A. Rosen-Wolff, A. M. J. Peters, M. C. Sneller, C. W. Hallahan, J. Wang, et al.
The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis
Blood,
July 1, 2001;
98(1):
194 - 200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Lopatin, X. Yao, R. K. Williams, J. J. H. Bleesing, J. K. Dale, D. Wong, J. Teruya-Feldstein, S. Fritz, M. R. Morrow, I. Fuss, et al.
Increases in circulating and lymphoid tissue interleukin-10 in autoimmune lymphoproliferative syndrome are associated with disease expression
Blood,
May 15, 2001;
97(10):
3161 - 3170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. DeFranco, S. Bonissoni, F. Cerutti, G. Bona, F. Bottarel, F. Cadario, A. Brusco, G. Loffredo, I. Rabbone, A. Corrias, et al.
Defective Function of Fas in Patients With Type 1 Diabetes Associated With Other Autoimmune Diseases
Diabetes,
March 1, 2001;
50(3):
483 - 488.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. D. Klonowski and M. Monestier
Heavy Chain Revision in MRL Mice: A Potential Mechanism for the Development of Autoreactive B Cell Precursors
J. Immunol.,
October 15, 2000;
165(8):
4487 - 4493.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Comi, M. Leone, S. Bonissoni, S. DeFranco, F. Bottarel, C. Mezzatesta, A. Chiocchetti, F. Perla, F. Monaco, and U. Dianzani
Defective T cell Fas function in patients with multiple sclerosis
Neurology,
October 10, 2000;
55(7):
921 - 927.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Waalkes, D. A. Fox, J. C. States, S. R. Patierno, and M. J. McCabe Jr.
Metals and Disorders of Cell Accumulation: Modulation of Apoptosis and Cell Proliferation
Toxicol. Sci.,
August 1, 2000;
56(2):
255 - 261.
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Ramenghi, S. Bonissoni, G. Migliaretti, S. DeFranco, F. Bottarel, C. Gambaruto, D. DiFranco, R. Priori, F. Conti, I. Dianzani, et al.
Deficiency of the Fas apoptosis pathway without Fas gene mutations is a familial trait predisposing to development of autoimmune diseases and cancer
Blood,
May 15, 2000;
95(10):
3176 - 3182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Gronbaek, T. Dalby, J. Zeuthen, E. Ralfkiaer, and P. Guldberg
The V410I (G1228A) variant of the caspase-10 gene is a common polymorphism in the Danish population
Blood,
March 15, 2000;
95(6):
2184 - 2185.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Greiner, J. O. Armitage, and T. G. Gross
Atypical Lymphoproliferative Diseases
Hematology,
January 1, 2000;
2000(1):
133 - 146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Whitekus, R. P. Santini, A. J. Rosenspire, and M. J. McCabe Jr.
Protection Against CD95-Mediated Apoptosis by Inorganic Mercury in Jurkat T Cells
J. Immunol.,
June 15, 1999;
162(12):
7162 - 7170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Algeciras-Schimnich, T. S. Griffith, D. H. Lynch, and C. V. Paya
Cell Cycle-Dependent Regulation of FLIP Levels and Susceptibility to Fas-Mediated Apoptosis
J. Immunol.,
May 1, 1999;
162(9):
5205 - 5211.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Straus, M. Sneller, M. J. Lenardo, J. M. Puck, and W. Strober
An Inherited Disorder of Lymphocyte Apoptosis: The Autoimmune Lymphoproliferative Syndrome
Ann Intern Med,
April 6, 1999;
130(7):
591 - 601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Lamy, J. H. Liu, T. H. Landowski, W. S. Dalton, and T. P. Loughran Jr
Dysregulation of CD95/CD95 Ligand-Apoptotic Pathway in CD3+ Large Granular Lymphocyte Leukemia
Blood,
December 15, 1998;
92(12):
4771 - 4777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Lim, S. E. Straus, J. K. Dale, T. A. Fleisher, M. Stetler-Stevenson, W. Strober, M. C. Sneller, J. M. Puck, M. J. Lenardo, K. S. J. Elenitoba-Johnson, et al.
Pathological Findings in Human Autoimmune Lymphoproliferative Syndrome
Am. J. Pathol.,
November 1, 1998;
153(5):
1541 - 1550.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. H. Landowski, N. Qu, I. Buyuksal, J. S. Painter, and W. S. Dalton
Mutations in the Fas Antigen in Patients With Multiple Myeloma
Blood,
December 1, 1997;
90(11):
4266 - 4270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
