An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome.

Abstract:

:The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that regulate lymphocyte homeostasis and underlie the development of autoimmunity. 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.

journal_name

Ann Intern Med

authors

Straus SE,Sneller M,Lenardo MJ,Puck JM,Strober W

doi

10.7326/0003-4819-130-7-199904060-00020

subject

Has Abstract

pub_date

1999-04-06 00:00:00

pages

591-601

issue

7

eissn

0003-4819

issn

1539-3704

pii

199904060-00009

journal_volume

130

pub_type

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