The following is a summary of “Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity,” published in the OCTOBER 2023 issue of Allergy & Immunology by Maccari, et al.

Activated phosphoinositide-3-kinase δ syndrome (APDS) represents an inborn error of immunity (IEI) characterized by infection susceptibility and immune dysregulation. It shares clinical features with other disorders. Disease management depends on its evolution, but predicting severe disease remains challenging. For a study, researchers sought to expand the understanding of disease manifestations in APDS1 versus APDS2, compare these with other IEIs such as CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease, and identify predictors of disease severity in APDS.

Data were collected from the ESID (European Society for Immunodeficiencies)-APDS registry and compared to published cohorts of other IEIs.

The analysis of 170 APDS patients highlighted the high penetrance and early onset of APDS compared to other IEIs. It demonstrated significant clinical heterogeneity, even in individuals with the same PIK3CD variant (E1021K), indicating that genotype poorly predicts phenotype and disease course. Extensive clinical overlap between APDS and other IEIs suggested a convergence of affected pathways. Specific affected organ systems were identified: bronchiectasis was typical of APDS1, while interstitial lung disease and enteropathy were more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies were most frequent in STAT3 GOF, while growth impairment was common in APDS2. Early clinical onset was identified as a risk factor for severe disease in APDS.

APDS showcased how a single genetic variant can lead to a diverse autoimmune-lymphoproliferative phenotype. While there was substantial overlap with other IEIs, certain features can distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease, suggesting the need for specific treatment studies in younger APDS patients.

Source: jacionline.org/article/S0091-6749(23)00812-6/fulltext