ABSTRACT
BACKGROUND: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. OBJECTIVES: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS. METHODS: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. RESULTS: The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. CONCLUSIONS: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
Subject(s)
Phosphatidylinositol 3-Kinase , Primary Immunodeficiency Diseases , Humans , Phosphatidylinositol 3-Kinase/genetics , Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases , CTLA-4 Antigen/genetics , Mutation , Primary Immunodeficiency Diseases/genetics , RegistriesABSTRACT
The early diagnosis of metastatic pulmonary calcification is beneficial, as some patients may develop restrictive changes in respiratory function or in some cases lethal acute respiratory distress. The aim of the study was to evaluate whether scanning with 99(m)Tc DPD might be useful in early diagnosis of pulmonary calcification in setting of chronic renal failure and hemodialysis and if presence of pulmonary calcification is associated with an abnormality in respiratory parameters. Forty-two patients with end-stage renal disease, who were treated by regular haemodialysis, were investigated. Twenty five (59.5%) out of forty two patients had increased lung uptake of 99(m)Tc DPD at whole body scintigraphy-grade 2 group. These patients were on dialysis 149±26 months compared with 57±16 months in 17 patients with a normal lung uptake of 99(m)Tc DPD at whole body scintigraphy- grade 1 group (p<0.01). In grade 2 group 22 patients (88%) had significantly lower (p<0.01) parameters of spirometry (FEF25-75, FEF75 FEF50, FEF25) compared to predicted values while in grade 1 group the parameters were significantly lower in only six patients (35.3%). There was statistically insignificant difference between these two groups regarding parathyroid hormone level (p>0.05). These observations confirm previous findings that scintigraphy with 99(m)Tc DPD may be efficious in early diagnosis of pulmonary calcification in hemodialised patients as well as the fact that spirometry is useful in patients with confirmed pulmonary calcifications.
