Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

Background: Activated phosphoinositide-3-kinase d 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. (J Allergy Clin Immunol 2023;152:984-96.

Apport du TEP-scan dans le diagnostic positif de la sarcoïdose, au cours du bilan d’uvéite indéterminée [Role of PET-​scan in the positive diagnosis of sarcoidosis in the work-​up of uveitis]

National audienc

Systemic light chain amyloidosis and Sjogren syndrome: an uncommon association.

International audienceSjogren syndrome is associated with lymphoproliferative disease in 7% of cases; however, association with AL amyloidosis is uncommon. We present a patient who presented simultaneously with Sjogren syndrome (supported by dry mouth, positive Schirmer's test, anti-Ro/SSA antibodies, and a lower lip salivary gland biopsy) and AL amyloidosis revealed by heart failure without myeloma. Although is it know that amyloidosis can masquerade as Sjogren syndrome, the occurrence of simultaneous AL amyloidosis and primary Sjogren syndrome has been reported rarely

Role of serum immunoglobulins for predicting sarcoidosis outcome A cohort study

International audienceBackground - Sarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis.Methods - We conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients.Results - Eighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01-1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4-24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years.Conclusions - There was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.<br

Prognostic value and predictors of the alteration of the diffusing capacity of the lungs for carbon monoxide in systemic lupus erythematosus

International audienceOBJECTIVES: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by heterogeneous manifestations and severity, with frequent lung involvement. Among pulmonary function tests (PFT), the measure of the diffusing capacity of the lungs for carbon monoxide (DLCO) is a noninvasive and sensitive tool assessing pulmonary microcirculation. Asymptomatic and isolated DLCO alteration has been frequently reported in SLE, but its clinical relevance has not been established. METHODS: This retrospective study focused on 232 SLE patients fulfilling the 2019 EULAR/ACR classification criteria for SLE. Data were collected from the patient’s medical record, including demographic, clinical, and immunological characteristics while DLCO was measured when performing PFT as part of routine patient follow-up. RESULTS: At the end of follow-up, DLCO alteration (&lt;70% of predicted value) was measured at least once in 154 patients (66.4%), and was associated with a history of smoking as well as interstitial lung disease (ILD), but was also associated with renal and neurological involvement. History of smoking, detection of anti-nucleosome autoantibodies and clinical lymphadenopathy at diagnosis were independent predictors of DLCO alteration, while early cutaneous involvement with photosensitivity was a protective factor. DLCO alteration, at baseline or anytime during follow-up was predictive of admission in intensive care unit and/or of all-cause death, both mainly due to severe disease flares and premature cardiovascular complications. CONCLUSION: This study suggests a link between DLCO alteration and disease damage, potentially related to SLE vasculopathy, and prognostic value of DLCO on death or ICU admission in SLE

11q24.2q24.3 microdeletion in two families presenting features of Jacobsen syndrome, without intellectual disability Role of FLI1, ETS1, and SENCR long noncoding RNA

International audienceThis report presents two families with interstitial 11q24.2q24.3 deletion, associated with malformations, hematologic features, and typical facial dysmorphism, observed in Jacobsen syndrome (JS), except for intellectual disability (ID). The smallest 700 Kb deletion contains only two genes FLI1 and ETS1, and a long noncoding RNA, SENCR, narrowing the minimal critical region for some features of JS. Consistent with recent literature, it adds supplemental data to confirm the crucial role of FLI1 and ETS1 in JS, namely FLI1 in thrombocytopenia and ETS1 in cardiopathy and immune deficiency. It also supports that combined ETS1 and FLI1 haploinsufficiency explains dysmorphic features, notably ears, and nose anomalies. Moreover, it raises the possibility that SENCR, a long noncoding RNA, could be responsible for limb defects, because of its early role in endothelial cell commitment and function. Considering ID and autism spectrum disorder, which are some of the main features of JS, a participation of ETS1, FLI1, or SENCR cannot be excluded. But, considering the normal neurodevelopment of our patients, their role would be either minor or with an important variability in penetrance. Furthermore, according to literature, ARHGAP32 and KIRREL3 seem to be the strongest candidate genes in the 11q24 region for other Jacobsen patients

Study profile.

<p>CS = Corticosteroids; FU = Follow-Up; SPE = Serum Protein Electrophoresis.</p

Features associated with corticosteroid therapy in multivariate analysis.

<p>Features associated with corticosteroid therapy in multivariate analysis.</p

Splenectomy for haemophagocytic lymphohistiocytosis of unknown origin: risks and benefits in 21 patients

International audienceNo abstract availabl