UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstracts for References 3,4

of 'Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis'

3
TI
Autoimmune lymphoproliferative syndrome (ALPS).
AU
Bleesing JJ
SO
Curr Pharm Des. 2003;9(3):265.
 
In patients with ALPS, defective homeostasis of lymphocytes is reflected in abnormal accumulation of lymphocytes, leading to lymphadenopathy, (hepato)splenomegaly and hypersplenism, autoimmunity due to a failure to remove autoreactive lymphocytes, and inappropriate survival of lymphocytes associated with an increased occurrence of lymphoma. Several of the laboratory findings are unique for ALPS and reflect defective Fas-mediated apoptosis and abnormal immune regulation. Much has been learned about the molecular mechanisms that underlie defective Fas-mediated apoptosis and the complex relationship between genotype, phenotype and disease penetrance. Family studies strongly suggest the contribution of one or more additional factors to the pathogenesis of ALPS. This may pertain to defective immunoregulation by an altered IL-2/IL-2 receptor system, reflected in the specific loss of CD4+/CD25+ T cells, and/or by the highly increased IL-10 levels, but other factors may equally be involved. Treatment strategies remain mostly targeted at the disease manifestations, but more specific therapies directed at the primary pathogenic defects themselves might become possible in the future. Continued efforts directed at both careful clinical follow-up and basic scientific investigation are needed to increase our understanding of the incidence, natural history, and pathogenesis of ALPS. In return, this may prove of benefit for the understanding of autoimmune disease in general.
AD
Arkansas Children's Hospital Research Institute, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA. bleesingjacobh@uams.edu
PMID
4
TI
Cell-death signaling and human disease.
AU
Rieux-Laucat F, Fischer A, Deist FL
SO
Curr Opin Immunol. 2003;15(3):325.
 
The autoimmune lymphoproliferative syndrome (ALPS) in humans and the lpr mouse strain are the first examples of primary apoptosis defects caused by inherited death-receptor mutations. They illustrate the role of Fas and Fas ligand in the control of autoimmune T-cell and B-cell proliferation. Subsequent analyses of ALPS in humans have highlighted the role of caspase 10 in the induction of apoptosis. The recent identification of a human caspase 8 defect has revealed a potential connection between apoptosis pathways and immune-receptor signaling. The genetic basis of ALPS is extremely complex, as multiple factors are potentially involved in the pathogenesis of this disease, thus offering an interesting model with which to unravel the mechanisms involved in T-cell homeostasis and self-tolerance.
AD
Institut National de la santéet de la Recherche Médicale U429, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France. rieux@necker.fr
PMID