Abstract
Activated phosphoinositide 3-kinase δ syndrome (APDS), also known as PASLI disease (p110d-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency) are combined immunodeficiencies resulting from gain-of-function mutations in the genes (PIK3CD and PIK3R1) encoding the subunits of phosphoinositide 3-kinase δ (PI3Kδ) and were first described in 2013. These mutations result in the hyperactivation of the PI3K/AKT/mTOR/S6K signally pathways. In this mini-review we have detailed the current treatment options for APDS. These treatments including conventional immunodeficiency therapies such as immunoglobulin replacement, antibiotic prophylaxis, and hematopoietic stem cell transplant. We also discuss the more targeted therapies of mTOR inhibition with sirolimus and selective PI3Kδ inhibitors.
Highlights
Activated phosphoinositide 3-kinase δ syndrome (APDS), known as PASLI disease (p110d-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency) is a combined immunodeficiency resulting from dominant, gain-of-function mutations in the genes encoding p110δ (PIK3CD) and p85α (PIK3R1), the catalytic and regulatory subunits of phosphoinositide 3-kinase δ (PI3Kδ)
Our increasing understanding of the underlying mechanism of APDS suggests a role for more targeted treatment in this disorder such as direct inhibition of the activated PI3Kδ by selective PI3Kδ inhibitors or inhibition of the downstream mTOR pathway by Sirolimus [3, 7]. In this mini-review will we review how APDS is treated, examining the experience of using conventional immune deficiency therapies in APDS including haematopoietic stem cell transplant (HSCT), and the more recent experience of selective PI3Kδ inhibitors and Sirolimus
Disseminated BCGosis and other mycobacterial infections have not been reported in APDS, and so whilst individual patients have been treated for local bacillus Calmette Guèrin (BCG) infections, APDS patients are not routinely placed on antimycobacterial prophylaxis
Summary
Individuals with APDS often have demonstrable antibody deficiency and lymphopenia and recurrent infections. These complications have led immunologists to treat APDS with standard supportive therapies such as prophylactic antibiotic therapy, immunoglobulin replacement therapy (IRT), and HSCT. [4] and [5] revealed the frequency of conventional treatments in patients with APDS These complications have led immunologists to treat APDS with standard supportive therapies such as prophylactic antibiotic therapy, immunoglobulin replacement therapy (IRT), and HSCT. [4] and [5] revealed the frequency of conventional treatments in patients with APDS
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