Prevalence of autoantibodies in the course of Gaucher disease type 1: A multicenter study comparing Gaucher disease patients to healthy subjects

Objectives

Type 1 Gaucher disease may be related to the presence of autoantibodies. Their clinical significance is questioned.Primary endpoint was to compare the prevalence of autoantibodies in type 1 Gaucher disease patients with healthy subjects, seeking correlations with autoimmune characteristics. Secondary endpoints were to determine whether patients with autoantibodies reported autoimmunity-related symptoms and if genotype, splenectomy or treatment influenced autoantibodies presence.

Cardiopulmonary,biomarkers, and vascular responses to acute hypoxia following cardiac transplantation

Previous studies have suggested good adaptation of cardiac transplant (CTx) recipients to exposure to a high altitude. No studies have investigated the cardiopulmonary and biomarker responses to acute hypoxic challenges following CTx. Thirty‐six CTx recipients and 17 age‐matched healthy controls (HC) were recruited. Sixteen (16) patients (42%) had cardiac allograft vasculopathy (CAV). Cardiopulmonary responses to maximal and submaximal exercise at 21% O₂, 20‐minutes hypoxia (11.5% O₂), and following a 10‐minute exposure to 11.5% O₂ using 30% of peak power output were completed. Vascular endothelial growth factor (VEGF), interleukin‐6 (IL‐6), suppression of tumorigenicity 2 (ST2) were measured at baseline and at peak stress. Endothelial peripheral function was assessed using near‐infrared spectroscopy. Compared with HC, CTx presented a lesser O₂ desaturation both at rest (?19.4 ± 6.8 [CTx] vs ?24.2 ± 6.0% O₂ [HC], P < 0.05) and following exercise (?23.2 ± 4.9 [CTx] vs ?26.2 ± 4.7% O₂ [HC], P < 0.05). CTx patients exhibited a significant decrease in peak oxygen uptake. IL‐6 and VEGF levels were significantly higher in CTx recipients in basal conditions but did not change in response to acute stress. CTx patients exhibit a favorable ventilatory and overall response to hypoxic stress. These data provide further insights on the good adaptability of CTx to exposure to high altitude.     

Loss of function IFT27 variants associated with an unclassified lethal fetal ciliopathy with renal agenesis

Ciliopathies comprise a group of clinically heterogeneous and overlapping disorders with a wide spectrum of phenotypes ranging from prenatal lethality to adult‐onset disorders. Pathogenic variants in more than 100 ciliary protein‐encoding genes have been described, most notably those involved in intraflagellar transport (IFT) which comprises two protein complexes, responsible for retrograde (IFT‐A) and anterograde transport (IFT‐B). Here we describe a fetus with an unclassified severe ciliopathy phenotype including short ribs, polydactyly, bilateral renal agenesis, and imperforate anus, with compound heterozygosity for c.118_125del, p.(Thr40Glyfs*11) and a c.352 +1G > T in IFT27, which encodes a small GTPase component of the IFT‐B complex. We conclude that bilateral renal agenesis is a rare feature of this severe ciliopathy and this report highlights the phenotypic overlap of Pallister–Hall syndrome and ciliopathies. The phenotype in patients with IFT27 gene variants is wide ranging from Bardet–Biedl syndrome to a lethal phenotype.