Activated PI3K delta syndrome

Activated PI3K delta syndrome (APDS) is a primary immunodeficiency disease caused by activating gain of function mutations in the PIK3CD gene.^[7][8][2]

Activated PI3K delta syndrome
Other names	immunodeficiency 14, p110δ-activating mutation causing senescent T cells, PASLI
Activated PI3K Delta Syndrome is autosomal dominant
Symptoms	Immunodeficiency, Lymphadenopathy[1]
Causes	Mutation in phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform[2][3]
Diagnostic method	Genetic testing[4]
Treatment	Antiviral therapy[5][6]

Symptoms and signs

The signs and symptoms of activated PI3K Delta Syndrome are consistent with the following:^[1]

• Immunodeficiency
• Lymphadenopathy
• Sinopulmonary infections
• Bronchiectasis

Cause

In terms of genetics, activated PI3K Delta Syndrome is autosomal dominant, a mutation in phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform is the reason for this condition (located at chromosome 1p36.) ^[2][3]

Mechanism

PI3kinase

The pathophysiology of activated PI3K delta syndrome has several aspects.^[2] The normal function has P110δ (PI3K) involved in immune system regulation.^[9]

P110δ effect is not limited to the immune system; P110δ has a presence in transformed epithelial cells and cell adhesion molecules (airway inflammation), and research has been done on the possibility of P110δ in the nervous system.^[10]

Activated PI3K delta syndrome effect indicates affected individuals are likely to have activation-induced cell death.^[2] Normally, PI3K-delta signaling assists B cells and T cells to mature; however, overactive PI3K-delta has an effect on the B and T cell differentiation (the process by which cells eventually are different from one another^[11]).

Consequently, there is an inability to confront an infection, as well as early cell death. Furthermore, overproduction of said signal can cause lymphadenopathy (which is an enlargement of lymph nodes^[12]) due to excess white blood cells.^[7]

Diagnosis

In order to ascertain if an individual has activated PI3K delta syndrome, usually one finds atypical levels of immunoglobulins. Methods to determine the condition are the following:^[4]

• Genetic testing
• Laboratory findings
• Symptoms exhibited

Treatment

Amoxicillin(antibiotic)

Infections for this condition, are treated or prevented in the following general ways:^[5][6]

• Bacterial infection should be treated rapidly (with antibiotics)
• Antiviral therapy
• Modify lifestyle (exposure to pathogens need to be minimized)

Leniolisib (Joenja) was approved for medical use in the United States in March 2023.^[13][14][15] It is the first approved drug in the US for activated PI3K delta syndrome.^[13]