Alberto Clivio alberto at
Wed Nov 29 05:40:25 EST 2000

This syndrome arises early in childhood in persons who inherit mutations
in genes that mediate apoptosis, or programmed cell death. The timely
deletion of lymphocytes is a way to prevent their accumulation and the
persistence of cells that can react against the body's own antigens. In
ALPS, defective lymphocyte apoptosis permits chronic, nonmalignant
adenopathy and splenomegaly; the survival of normally uncommon
"double-negative" CD3+ CD4- CD8- T cells; and the development of
autoimmune disease. Most cases of ALPS involve heterozygous mutations in
the lymphocyte surface protein Fas that impair a major apoptotic
pathway. Detailed immunologic
investigations of the cellular and cytokine profiles in ALPS show a
prominent skewing toward a T-helper 2 phenotype; this provides a
rational explanation for the humoral autoimmunity typical of patients
with ALPS. Prospective evaluations of 26 patients and their families
show an ever-expanding spectrum of ALPS and its major complications:
hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and
neutropenia. Defective apoptosis may also contribute to a heightened
risk for lymphoma.

You might be interested in having a look at the following references:

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     Transfusion. 40(8):943-8, 2000 Aug.

     Shenoy S. Arnold S. Chatila T.
     Response to steroid therapy in autism secondary to
     autoimmune lymphoproliferative syndrome
     Journal of Pediatrics. 136(5):682-7, 2000 May.

     Jackson CE. Fischer RE. Hsu AP. Anderson SM. Choi Y. Wang J. Dale
JK. Fleisher TA.           Middelton LA. Sneller MC. Lenardo MJ. Straus
SE. Puck JM.
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     van der Burg M. de Groot R. Comans-Bitter WM. den Hollander JC.
Hooijkaas H. Neijens HJ. Berger RM. Oranje AP. Langerak AW. van Dongen
     Autoimmune lymphoproliferative syndrome (ALPS) in a child from
consanguineous parents: a dominant or recessive disease?.
    Pediatric Research. 47(3):336-43, 2000 Mar.

     Kraus MD. Shenoy S. Chatila T. Hess JL.
     Light microscopic, immunophenotypic, and molecular genetic study of

     autoimmune lymphoproliferative syndrome
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     Aspinall AI. Pinto A. Auer IA. Bridges P. Luider J. Dimnik L. Patel
KD. Jorgenson K. Woodman RC.
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     Blood Cells, Molecules, & Diseases. 25(3-4):227-38, 1999

     Jackson CE. Puck JM.
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     Wang J. Zheng L. Lobito A. Chan FK. Dale J. Sneller M. Yao X. Puck
JM. Straus SE. Lenardo MJ.
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     Strobel P. Nanan R. Gattenlohner S. Muller-Deubert S.
Muller-Hermelink HK. Kreth HW. Marx A.
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     Martin DA. Zheng L. Siegel RM. Huang B. Fisher GH. Wang J. Jackson
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     Straus SE. Sneller M. Lenardo MJ. Puck JM. Strober W.
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     Sleight BJ. Prasad VS. DeLaat C. Steele P. Ballard E. Arceci RJ.
Sidman CL.
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     Lim MS. Straus SE. Dale JK. Fleisher TA. Stetler-Stevenson M.
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     Puck JM. Sneller MC.
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     Sneller MC. Wang J. Dale JK. Strober W. Middelton LA. Choi Y.
Fleisher TA. Lim MS. Jaffe ES. Puck JM. Lenardo MJ. Straus SE.
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     Bettinardi A. Brugnoni D. Quiros-Roldan E. Malagoli A. La Grutta S.
Correra A. Notarangelo LD.
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