🔬 Other

Autoimmune Lymphoproliferative Syndrome

Also known as: ALPS, Canale-Smith Syndrome

Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare genetic disorder characterized by a failure of lymphocyte homeostasis, leading to chronic, non-malignant lymphoproliferation, autoimmunity, and an increased risk of lymphoma. The underlying defect involves impaired apoptosis (programmed cell death) of lymphocytes, resulting in their accumulation in lymphoid organs and subsequent autoimmune manifestations.

ICD-10: D89.813 Orphanet: 79247 OMIM: 601859
👥 Estimated 1 in 1,000,000 Prevalence
🔬 15 Active Trials

Imagine your body's immune system has soldiers that don't know when to stop fighting. In ALPS, these soldiers (lymphocytes) don't die when they should, causing swelling in your body and attacking healthy cells. Doctors can use medicine to calm down these soldiers and help them behave.

Signs & Symptoms

  • Chronic, non-malignant lymphadenopathy
  • Splenomegaly
  • Hepatomegaly
  • Autoimmune cytopenias (e.g., hemolytic anemia, thrombocytopenia, neutropenia)
  • Increased risk of lymphoma
  • Elevated levels of double-negative T cells (DNTs)
  • Increased susceptibility to infections
  • Uveitis
  • Glomerulonephritis
  • Arthritis

Treatment Options

MEDICATION FDA Approved

Immunosuppressants (e.g., sirolimus, mycophenolate mofetil)

MODERATELY EFFECTIVE
MEDICATION FDA Approved

Corticosteroids (e.g., prednisone)

MODERATELY EFFECTIVE
THERAPY FDA Approved

Intravenous immunoglobulin (IVIG)

MODERATELY EFFECTIVE
MEDICATION FDA Approved

Rituximab (anti-CD20 antibody)

MODERATELY EFFECTIVE
MEDICATION FDA Approved

Alemtuzumab (anti-CD52 antibody)

MODERATELY EFFECTIVE
THERAPY

Hematopoietic stem cell transplantation (HSCT)

HIGHLY EFFECTIVE
SUPPORTIVE

Supportive care (e.g., prophylactic antibiotics, vaccinations)

SUPPORTIVE

Diagnosis

  • Clinical evaluation
  • Complete blood count (CBC)
  • Immunophenotyping to detect elevated DNTs
  • Apoptosis assays to assess lymphocyte apoptosis
  • Genetic testing for mutations in FAS, FASLG, CASP10, or other related genes
  • Lymph node biopsy (if needed to rule out malignancy)

History

ALPS was first described in the 1990s, with the genetic basis being elucidated in subsequent years. The discovery of mutations in FAS and other apoptosis-related genes provided critical insights into the pathogenesis of the disease.

Recent Breakthroughs

2022

Targeted Therapies for ALPS

Ongoing research is focused on developing targeted therapies that specifically address the underlying defects in lymphocyte apoptosis, such as inhibitors of specific signaling pathways involved in lymphocyte survival.

2023

Improved Diagnostic Criteria for ALPS

Refinement of diagnostic criteria based on genetic and immunologic markers has improved the accuracy and speed of ALPS diagnosis, allowing for earlier intervention and management.