Autoimmune lymphoproliferative syndrome

From WikiMD.com Medical Encyclopedia

A rare genetic disorder affecting the immune system


Autoimmune lymphoproliferative syndrome
[[File:|250px|alt=|]]
Synonyms Canale-Smith syndrome
Pronounce
Field Immunology, Hematology, Pediatrics
Symptoms Lymphadenopathy, splenomegaly, autoimmune cytopenias, recurrent fevers, fatigue
Complications Hemolytic anemia, thrombocytopenia, neutropenia, increased risk of lymphoma
Onset Usually in early childhood
Duration Chronic
Types ALPS-FAS, ALPS-FASL, ALPS-CASP10, and others based on genetic mutation
Causes Mutations in the FAS gene or related genes involved in lymphocyte apoptosis
Risks Family history of ALPS or related immune disorders
Diagnosis Clinical symptoms, elevated double-negative T cells, genetic testing, biomarkers such as IL-10, vitamin B12, and sFASL
Differential diagnosis Common variable immunodeficiency, systemic lupus erythematosus, Evans syndrome, infectious mononucleosis
Prevention None known
Treatment Immunosuppressive therapy, corticosteroids, intravenous immunoglobulin (IVIG), splenectomy in severe cases
Medication Sirolimus, mycophenolate mofetil, rituximab, corticosteroids
Prognosis Variable; many respond well to treatment, but lifelong monitoring is often needed
Frequency Rare
Deaths Can occur from complications or progression to lymphoma


Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder characterized by the abnormal regulation of the immune system, leading to the proliferation of lymphocytes and the development of autoimmunity. This condition is primarily caused by mutations in genes that are crucial for the process of apoptosis, which is the programmed cell death necessary for maintaining immune system balance.

Pathophysiology[edit | edit source]

ALPS is primarily associated with mutations in the FAS gene, which encodes a protein that plays a critical role in the apoptotic pathway. The FAS protein is a cell surface receptor that, when bound to its ligand, initiates a cascade of events leading to cell death. Mutations in the FAS gene disrupt this process, resulting in the accumulation of lymphocytes, particularly T cells, and the development of lymphoproliferative disorders.

The failure of apoptosis in ALPS leads to the accumulation of autoreactive lymphocytes, which can attack the body's own tissues, causing autoimmune diseases. Common autoimmune manifestations in ALPS include autoimmune hemolytic anemia, immune thrombocytopenic purpura, and neutropenia.

Clinical Features[edit | edit source]

Patients with ALPS typically present with chronic lymphadenopathy and splenomegaly. The condition often manifests in early childhood, although the age of onset can vary. In addition to lymphoproliferation, individuals with ALPS may experience recurrent infections due to immune dysregulation and the presence of autoantibodies.

Other clinical features may include:

Diagnosis[edit | edit source]

The diagnosis of ALPS is based on clinical criteria, laboratory findings, and genetic testing. Key laboratory findings include elevated levels of double-negative T cells (TCRαβ+ CD4− CD8−) and increased serum levels of vitamin B12 and interleukin-10. Genetic testing can confirm mutations in the FAS gene or other related genes involved in the apoptotic pathway.

Management[edit | edit source]

Management of ALPS involves addressing both the lymphoproliferative and autoimmune components of the disease. Treatment options may include:

Prognosis[edit | edit source]

The prognosis for individuals with ALPS varies depending on the severity of the disease and the response to treatment. With appropriate management, many patients can lead relatively normal lives, although they may require ongoing monitoring and treatment for autoimmune complications.

Related pages[edit | edit source]

External links[edit | edit source]

Classification
External resources
WikiMD
Navigation: Wellness - Encyclopedia - Health topics - Disease Index‏‎ - Drugs - World Directory - Gray's Anatomy - Keto diet - Recipes

Search WikiMD

Ad.Tired of being Overweight? Try W8MD's physician weight loss program.
Semaglutide (Ozempic / Wegovy and Tirzepatide (Mounjaro / Zepbound) available.
Advertise on WikiMD

WikiMD's Wellness Encyclopedia

Let Food Be Thy Medicine
Medicine Thy Food - Hippocrates

Medical Disclaimer: WikiMD is not a substitute for professional medical advice. The information on WikiMD is provided as an information resource only, may be incorrect, outdated or misleading, and is not to be used or relied on for any diagnostic or treatment purposes. Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition. WikiMD expressly disclaims responsibility, and shall have no liability, for any damages, loss, injury, or liability whatsoever suffered as a result of your reliance on the information contained in this site. By visiting this site you agree to the foregoing terms and conditions, which may from time to time be changed or supplemented by WikiMD. If you do not agree to the foregoing terms and conditions, you should not enter or use this site. See full disclaimer.
Credits:Most images are courtesy of Wikimedia commons, and templates, categories Wikipedia, licensed under CC BY SA or similar.

Contributors: Prab R. Tumpati, MD