Genomic coordinate (human 10:88,964,050 FAS) & (19:34,268,066 mouse Fas).
Cytoband (10q23.31 human FAS) & (19qC1 mouse Fas).
Here I present: “Autoimmune Lymphoproliferative Syndrome“, Victor McKusick, Mendelian Inheritance in Man’, 1966. (FAS)自體免疫性淋巴增生症候群。 idc10=D89.82
INTRODUCTION.
Autoimmune Lymphoproliferative Syndrome (ALPS) is a genetic immune-regulation disorder in which the body fails to properly eliminate activated lymphocytes. This leads to chronic lymphoproliferation and autoimmunity, especially affecting blood cells.
Core Mechanism (the key idea):
ALPS is caused by defective apoptosis (programmed cell death) of lymphocytes, most commonly due to mutations in the FAS pathway:
FAS (CD95) – most common.
FAS ligand (FASLG)
CASP10 / CASP8
Because lymphocytes don’t die when they should, they accumulate and attack self tissues.
Hallmark Features.
1. Chronic lymphoproliferation.
Persistent lymphadenopathy.
Splenomegaly.
Often begins in childhood.
2. Autoimmune disease (especially hematologic).
Autoimmune hemolytic anemia.
Immune thrombocytopenia (ITP).
Autoimmune neutropenia.
May involve kidneys, liver, gut.
3. Characteristic immune abnormality.
Elevated double-negative T cells (DNTs)
→ CD3⁺ CD4⁻ CD8⁻ T cells (a diagnostic hallmark)
Diagnostic Clues.
Required findings usually include:
Chronic non-malignant lymphadenopathy or splenomegaly.
Elevated DNT cells
Defective lymphocyte apoptosis (functional testing).
Supporting laboratory findings.
High vitamin B12.
Elevated IL-10.
Elevated soluble FAS ligand.
Polyclonal hypergammaglobulinemia.
Genetic testing confirms subtype.
ALPS Subtypes (simplified).
Type Cause:
ALPS-FAS Germline FAS mutation (most common).
ALPS-sFAS Somatic FAS mutation.
ALPS-FASLG FAS ligand mutation.
ALPS-CASP10 Caspase-10 mutation.
Complications.
High risk of lymphoma (Hodgkin & non-Hodgkin).
Chronic cytopenias.
Organ damage from immune attack.
Infections (from immune dysregulation or treatment).
There is evidence that autoimmune lymphoproliferative syndrome is caused by mutation in the FAS-cell surface death receptor (FAS) gene encoded on genomic coordinate 10:88,964,050 and cytoband 10q23.31 in humans.
