ALPS

[Alberto Clivio]

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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