Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
T-cell immunodeficiency (click to enlarge the image).
ALPS is due to defects in Fas, Fas Ligand, caspases 8 or 10 which interfere with apoptosis, leading to failure to delete autoreactive clones.
Mutations in FAS or caspase 10 manifest as autoimmune lymphoproliferative syndrome (ALPS). In ALPS, lymphocytes do not get a signal to "die" and they accumulate in the lymphoid organs.
There is lymphadenopathy, splenomegaly, autoimmune anemia, and thrombocytopenia. There is an increased number of double negative (CD4-CD8-) alpha/beta T cells.
Abnormal apoptosis is a cardinal feature of the rare autosomal dominant condition autoimmune lymphoproliferative syndrome (ALPS).
ALPS manifests in early childhood with:
- lymphadenopathy
- hepatosplenomegaly
- autoimmune diseases such as hemolytic anemia, thrombocytopenia, and autoimmune neutropenia, often in combination (ie, Evans syndrome)
ALPS patients have inactivating mutations in:
- FasL (type Ib)
- Fas (type Ia)
- caspase-8 or caspase-10 (type II)
Mutations in Fas or FasL interfere with the elimination of activated lymphocytes following an infection.
The persistence of these cells leads to an expanded populations of lymphocytes and predisposes to autoimmune disease and lymphomas.
Diagnosis of ALPS is suggested by:
- chronic nonmalignant lymphoproliferation
- autoimmune phenomena
- Greater than 1 percent circulating CD4-/CD8- ("double negative") T-cells
Diagnosis of ALPS is confirmed by:
- defective in vitro Fas-mediated apoptosis
- increased plasma interleukin-10
- increased Fas-ligand
Sirolimus is an immunosuppressive agent that induces apoptosis in lymphocytes and may effective in patients with glucocorticoid-resistant disease.
References
Autoimmune lymphoproliferative syndrome (ALPS). OMIM, Johns Hopkins University, 2009.
Published: 08/29/2009
Updated: 08/10/2010
Abnormal apoptosis is a cardinal feature of the rare autosomal dominant condition autoimmune lymphoproliferative syndrome (ALPS).
ALPS manifests in early childhood with:
- lymphadenopathy
- hepatosplenomegaly
- autoimmune diseases such as hemolytic anemia, thrombocytopenia, and autoimmune neutropenia, often in combination (ie, Evans syndrome)
ALPS patients have inactivating mutations in:
- FasL (type Ib)
- Fas (type Ia)
- caspase-8 or caspase-10 (type II)
Mutations in Fas or FasL interfere with the elimination of activated lymphocytes following an infection.
The persistence of these cells leads to an expanded populations of lymphocytes and predisposes to autoimmune disease and lymphomas.
Diagnosis of ALPS is suggested by:
- chronic nonmalignant lymphoproliferation
- autoimmune phenomena
- Greater than 1 percent circulating CD4-/CD8- ("double negative") T-cells
Diagnosis of ALPS is confirmed by:
- defective in vitro Fas-mediated apoptosis
- increased plasma interleukin-10
- increased Fas-ligand
Sirolimus is an immunosuppressive agent that induces apoptosis in lymphocytes and may effective in patients with glucocorticoid-resistant disease.
References
Autoimmune lymphoproliferative syndrome (ALPS). OMIM, Johns Hopkins University, 2009.
Published: 08/29/2009
Updated: 08/10/2010
2 comments:
This is a nice review but I wanted to make a few comments.
1) ALPS presents with an increased number of CD4-CD8- alpha beta T cells not gamma delta T cells.
2)Also from what I have read, the Required criteria for ALPs are:
-Chronic nonmalignant lymphocyte accumulation including lymphadenopathy and or splenomegaly
-Increased peripheral CD4-CD8-TCRalpha/beta (DNT) cells
-(confirmed by)Defective in vitro lymphocyte apoptosis.
Ref: Clinical Immunology. 3rd edition. Edited by Robert R Rich et al. Chapter 14: pages 229-233.
In ALPS, peripheral blood analysis show increased numbers of B lymphocytes and increased numbers of mature CD3+, CD4-, CD8- T lymphocytes expressing alpha/beta T-cell receptors - not gamma/delta TCR. The text above was corrected. Thank you for your comment and the reference.
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