Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study

The immune system is very complicated, and sometimes, a mutation in a single protein can cause major problems.  One such protein is Phosphoinositide 3-kinase (PI3Kδ), which, may interfere with the body’s ability to fight off disease upon activation.  In this month’s issue of JACI, Coulter and colleagues look at 53 patients with Activated PI3Kδ Syndrome (APDS) (J Allergy Clin Immunol 2017; 139(2): 597-606).

These 53 patients were found worldwide, and the diagnosis was confirmed by genetic sequencing.  They then looked at the laboratory findings, radiographs, and other clinical features to better understand the presentation of APDS. 

All in all, the presentation of APDS was highly variable.  Some were asymptomatic through adulthood while others developed infections early in childhood, leading to death.  Three required a bone marrow transplantation.  The most common infectious complication was recurrent respiratory tract infections.  Much like other antibody deficiency syndromes, there was a high rate of bronchiectasis.  Almost half of patients had difficulty fighting viruses like herpes, EBV, and CMV.  Swollen lymph nodes and hepato-splenomegaly were also very common.

Interestingly, PI3K mutations didn’t just effect the ability to fight infections.  Eighteen also had inflammatory/autoimmune diseases, most commonly autoimmune cytopenias. Seventeen had nodular mucosal lymphoid hyperplasia and seven developed lymphoma.  Since PI3K3D is associated with the central nervous system, there was also noted to be a high rate of neurodevelopmental morbidity, ranging from speech delays to global developmental delay.

This study provides a description of APDS, a newly recognized form of immunodeficiency.  It can present in so many different ways, so physicians should keep an eye out in patients who have recurrent infections, especially those involving the respiratory tract or those due to herpes viruses.  Treatment with hematopoietic stem cell transplant may be curative, and clinical trials for selective PI3Kδ inhibitors are currently underway.