Patients, Families & Caregivers

What is APDS?

Activated PI3K delta syndrome (APDS) is a rare genetic disease that affects the body’s immune system. It is one of a group of diseases called primary immunodeficiencies, or PIDs.1 When the immune system is not working properly, patients with PIDs are more likely to get infections, swelling of lymph nodes and spleen, or autoimmune manifestations.1 First described in 2013, APDS is caused by changes in one of two genes that are part of our DNA and can affect both men and women.1,2

Globally, APDS affects approximately
1-2 per million people2

There is no approved treatment available for APDS and current management is based on treating the symptoms.3-6

Who can be affected?

Individuals affected by APDS will usually have inherited a faulty gene from one of their parents.1

There is a 50% chance an affected parent will pass an APDS gene on to their child.7 Sometimes the faulty gene can occur spontaneously, when neither parent is a carrier.7

With APDS, family planning becomes an important consideration, and genetic counselling may help you make those important decisions8

 

What are the features of APDS?

Not everyone with APDS is affected to the same extent and they may not experience the same symptoms.

The most common feature of APDS is repeated infections, especially of the lungs which can lead to irreversible lung damage (bronchiectasis), and also infections of the nose (sinuses), and ears.1

Other common features include swelling of the lymph nodes and spleen, other infections, unusually slow growth in children, chronic diarrhoea, and fever.1

People with APDS also have a high risk of lymphoid malignancy.3

APDS has a wide range of clinical features. Severe, persistent, and recurrent bacterial and viral infections may occur during childhood or later in life with. Young patients may be delayed in their development.1

Living with APDS can be a significant burden, and negatively affect quality of life due to frequent infections, hospitalisations and fatigue.10-12 Children with diseases affecting their immune system are also less able to cope with social situations, may miss significant amounts of schooling, and are more likely to suffer with anxiety and depression.11

Diagnosing APDS

APDS is usually suspected from the signs and symptoms that an individual displays, as described above. A diagnosis of APDS can only be confirmed with genetic testing and other complimentary laboratory tests.1

APDS has the potential to be life-threatening and so can reduce life expectancy.13 Reducing the time to diagnosis for APDS can help with getting treatment sooner and prevent symptoms from getting worse.

As there is a 50% of chance of APDS being passed from parent to child, family members of patients with APDS should also be genetically tested14

Management of APDS

Management of APDS is focused on the treatment of symptoms, involving a range of different therapy types including immunosuppressive therapies, prophylactic antimicrobials, and surgical interventions. Patients often need several different treatments to ease the varied symptoms associated with a faulty immune system.3-6

Current treatment options for the features of APDS6

Treatment What are they? What are they used for?

Prophylactic antimicrobials

Medications that kill bacteria, viruses or funguses

Preventing infections

Immunoglobulin replacement therapy

Antibodies to replace those the patient is missing

Reducing infections, such as those of the lungs, nose and ears

Immunosuppressants

Medications that lower the activity of the immune system

Stopping the patients’ immune system from attacking their own cells, which is one cause of symptoms in APDS

Sirolimus

A medication that repairs one of the disease-causing routes in APDS

Reducing the swelling in lymph nodes, the spleen and the liver

Bone marrow transplant

A procedure that replaces disease-causing bone marrow with healthy bone marrow

The faulty or missing immune cells that lead to symptoms of APDS come from the bone marrow, so replacing this with healthy marrow can potentially cure the disease, but there are risks involved

Resources and Additional Links

For additional information about APDS and other support resources,

  1. Activated PI3K Delta Syndrome: http://www.immunodeficiencyuk.org/static/media/up/IPOPIADPS.pdf (accessed June 2022).
  2. Clinical management of individuals with APDS and PIs: https://rarerevolutionmagazine.com/digitalspotlight/clinical-management-of-individuals-with-apds and-pi/ (accessed June 2022).
  3. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.
  4. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.
  5. Maccari ME, et al. Front Immunol. 2018;9: Article 543.
  6. Coulter TI, Cant AJ. Front Immunol. 2018;9:2043.
  7. Genetic diagnosis of PIDs: https://ipopi.org/wp-content/uploads/2021/02/WEB_IPOPI_GeneticDiagnosis.pdf (accessed June 2022).
  8. Chapel H, et al. Front Immunol. 2014;5:627.
  9. Singh A, et al. Genes Dis. 2019;7(1): 67-74.
  10. Rider NL, et al. J Clin Immunol. 2017;37(5):461-475.
  11. Kuburovic NB, et al. Patient Prefer Adherence. 2014;8:323-330.
  12. Hajjar J, et al. J clin Immunol. 2017;37(2):153-165.
  13. Gathmann B, et al. J Allergy Clin Immunol. 2014;134(1):116-26. 15
  14. Chinn IK, et al. J Allergy Clin Immunol. 2020;145(1):46-69.

APD-INT-2022-0056    Date of preparation: August 2022

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