تسجيل الدخول

تسجيل

Autoimmune lymphoproliferative syndrome

المؤلف:  Longo, D., Fauci, A. S., Kasper, D. L., Hauser, S., Jameson, J. L., Loscalzo, J., Holland, S. M., & Langford, C. A.

المصدر:  Harrisons Principles of Internal Medicine (2025)

الجزء والصفحة:  22e , p2803

2026-02-25

470

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by nonmalignant T and B lymphoproliferation causing splenomegaly and enlarged lymph nodes; 70% of patients also display autoimmune manifestations such as autoimmune cytopenias, Guillain-Barré syndrome, uveitis, and hepatitis. A hallmark of ALPS is the presence of CD4–CD8– TCRαβ+ T cells (2–50%) in the blood of affected individuals. Hypergammaglobulinemia involving IgG and IgA is also frequently observed. The syndrome is caused by a defect in Fas mediated apoptosis of lymphocytes, which can thus accumulate and mediate autoimmunity. Furthermore, ALPS can lead to malignancies.

Most patients carry a heterozygous mutation in the gene encoding Fas that is characterized by dominant inheritance and variable penetrance, depending on the nature of the mutation. A rare and severe form of the disease with early onset can be observed in patients carrying a biallelic mutation of Fas, which profoundly impairs the protein’s expression and/or function. Fas-ligand, caspase 10, caspase 8, and somatic neuroblastoma RAS viral oncogene homologue (NRAS) and KRAS mutations have also been reported in a few cases of ALPS. Many cases of ALPS have not been precisely delineated at the molecular level. A B cell–predominant ALPS has recently been found associated with a protein kinase Cδ gene mutation. Treatment of ALPS is essentially based on the use of proapoptotic drugs, which need to be carefully administered in order to avoid toxicity.