Cardinal clinical and diagnostic features of ALPS and APDS
| Genetic disease . | ALPS . | APDS . |
|---|---|---|
| Genes | FAS, FASLG, FADD | PIK3CD, PIK3R1 |
| Inheritance and penetrance | Autosomal dominant (FAS, FADD) Somatic variants (FAS) Incomplete penetrance | Autosomal dominant Complete penetrance |
| Pathobiology | Fas-mediated apoptosis | Increased PI3Kδ signal |
| Age of onset | Median 3 yrs | Median 1 yr |
| Lymphoproliferation | Splenomegaly and lymphadenopathy | Splenomegaly, lymphadenopathy, mucosa-associated lymphoid hyperplasia (airways and gut) Nodular lymphoid hyperplasia |
| Increased risk of lymphoma | Yes (∼10% prevalence) | Yes (∼30% prevalence) |
| Immunoglobulins | Hypergammaglobulinemia | Increased IgM, hypogammaglobulinemia Reduced IgA |
| Immunophenotype | No lymphopenia Elevated DNT cells Often low class-switched B cells | Lymphopenia Increased transitional B cells Reduced naïve and class-switched B cells Increased CD57+/CD8+ T cells |
| Autoimmune findings | Cytopenias, hepatitis, nephritis, uveitis | Cytopenias, enteropathy, hepatitis, cholangitis, bronchiectasis |
| Infection susceptibility | Not significant | Sinopulmonary infections Chronic herpes viral infections (EBV, CMV) |
| Biomarkers | Elevated serum vitamin B12, sFASL, and IL-10 levels | Increased pAkt and S6 phosphorylation |
| Immunomodulatory therapies | High-dose corticosteroids, IVIG mycophenolate mofetil | High-dose corticosteroids, IVIG, and rapamycin |
| Targeted therapy | mTOR inhibitor (rapamycin) | PI3K delta inhibitor (leniolisib) |
| Genetic disease . | ALPS . | APDS . |
|---|---|---|
| Genes | FAS, FASLG, FADD | PIK3CD, PIK3R1 |
| Inheritance and penetrance | Autosomal dominant (FAS, FADD) Somatic variants (FAS) Incomplete penetrance | Autosomal dominant Complete penetrance |
| Pathobiology | Fas-mediated apoptosis | Increased PI3Kδ signal |
| Age of onset | Median 3 yrs | Median 1 yr |
| Lymphoproliferation | Splenomegaly and lymphadenopathy | Splenomegaly, lymphadenopathy, mucosa-associated lymphoid hyperplasia (airways and gut) Nodular lymphoid hyperplasia |
| Increased risk of lymphoma | Yes (∼10% prevalence) | Yes (∼30% prevalence) |
| Immunoglobulins | Hypergammaglobulinemia | Increased IgM, hypogammaglobulinemia Reduced IgA |
| Immunophenotype | No lymphopenia Elevated DNT cells Often low class-switched B cells | Lymphopenia Increased transitional B cells Reduced naïve and class-switched B cells Increased CD57+/CD8+ T cells |
| Autoimmune findings | Cytopenias, hepatitis, nephritis, uveitis | Cytopenias, enteropathy, hepatitis, cholangitis, bronchiectasis |
| Infection susceptibility | Not significant | Sinopulmonary infections Chronic herpes viral infections (EBV, CMV) |
| Biomarkers | Elevated serum vitamin B12, sFASL, and IL-10 levels | Increased pAkt and S6 phosphorylation |
| Immunomodulatory therapies | High-dose corticosteroids, IVIG mycophenolate mofetil | High-dose corticosteroids, IVIG, and rapamycin |
| Targeted therapy | mTOR inhibitor (rapamycin) | PI3K delta inhibitor (leniolisib) |
CMV, cytomegalovirus.