Aerobic physical capacity and health-related quality of life in children with sickle cell disease.

BACKGROUND: Aerobic fitness is a predictor of cardiovascular health which correlates with health-related quality of life in the general population. The aim is to evaluate the aerobic capacity by cardiopulmonary exercise test (CPET) in children with sickle cell disease in comparison with healthy matched controls. METHODS: Controlled cross-sectional study. RESULTS: A total of 72 children (24 with sickle cell disease and 48 healthy controls), aged 6-17 years old were enrolled. Children with sickle cell disease had a poor aerobic capacity, with median VO2max Z-score values significantly lower than matched controls (-3.55[-4.68; -2.02] vs. 0.25[-0.22; 0.66], P < 0.01, respectively), and a high proportion of 92% children affected by an impaired aerobic capacity (VO2max Z-score < -1.64). The VO2max decrease was associated with the level of anemia, the existence of a homozygote HbS/S mutation, restrictive lung disease and health-related quality of life. CONCLUSION: Aerobic capacity is poor in children with sickle cell disease. VO2max decrease is associated with the level of anemia, the existence of a homozygote HbS/S mutation, lung function, and health-related quality of life. These results represent a signal in favor of early initiation of cardiac rehabilitation in patients with sickle cell disease. CLINICAL TRIALS: NCT05995743. IMPACT: Aerobic fitness is a predictor of cardiovascular health which correlates with health-related quality of life in the general population. Aerobic capacity (VO2max) is poor in children with sickle cell disease, despite the absence of any pattern of heart failure. VO2max decrease was associated with the level of anemia, the existence of a homozygote HbS/S mutation, restrictive lung disease, and health-related quality of life. These results are in favor of early initiation of cardiac rehabilitation in children with sickle cell disease.

Severe Perinatal Presentations of Günther's Disease: Series of 20 Cases and Perspectives.

(1) Background: Congenital erythropoietic porphyria (CEP), named Günther's disease, is a rare recessive type of porphyria, resulting from deficient uroporphyrinogen III synthase (UROS), the fourth enzyme of heme biosynthesis. The phenotype ranges from extremely severe perinatal onset, with life-threatening hemolytic anaemia, to mild or moderate cutaneous involvement in late-onset forms. This work reviewed the perinatal CEP cases recorded in France in order to analyse their various presentations and evolution. (2) Methods: Clinical and biological data were retrospectively collected through medical and published records. (3) Results: Twenty CEP cases, who presented with severe manifestations during perinatal period, were classified according to the main course of the disease: antenatal features, acute neonatal distress and postnatal diagnosis. Antenatal symptoms (seven patients) were mainly hydrops fetalis, hepatosplenomegaly, anemia, and malformations. Six of them died prematurely. Five babies showed acute neonatal distress, associated with severe anemia, thrombocytopenia, hepatosplenomegaly, liver dysfunction, and marked photosensitivity leading to diagnosis. The only two neonates who survived underwent hematopoietic stem cell transplantation (HSCT). Common features in post-natal diagnosis (eight patients) included hemolytic anemia, splenomegaly, skin sensitivity, and discoloured teeth and urine. All patients underwent HSCT, with success for six of them, but with fatal complications in two patients. The frequency of the missense variant named C73R is striking in antenatal and neonatal presentations, with 9/12 and 7/8 independent alleles, respectively. (4) Conclusions: The most recent cases in this series are remarkable, as they had a less fatal outcome than expected. Regular transfusions from the intrauterine period and early access to HSCT are the main objectives.

Case Report: Persistency Pneumococcal Polysaccharide in Cerebrospinal Fluid During a Post Pneumococcal Chronic Aseptic Meningitis: Coincidental or (Auto-)Inflammatory Embers.

We report the case of a 9-months-old boy that has presented a steroid-dependent post-pneumococcal chronic aseptic meningitis was associated with persistence of pneumococcal cell wall components in cerebrospinal fluid during more than 20 months. Suggesting that this antigenic persistence could be involved in post-infectious manifestations through innate immunity response.

Differential Accumulation and Activation of Monocyte and Dendritic Cell Subsets in Inflamed Synovial Fluid Discriminates Between Juvenile Idiopathic Arthritis and Septic Arthritis.

Despite their distinct etiology, several lines of evidence suggest that innate immunity plays a pivotal role in both juvenile idiopathic arthritis (JIA) and septic arthritis (SA) pathophysiology. Indeed, monocytes and dendritic cells (DC) are involved in the first line of defense against pathogens and play a critical role in initiating and orchestrating the immune response. The aim of this study was to compare the number and phenotype of monocytes and DCs in peripheral blood (PB) and synovial fluid (SF) from patients with JIA and SA to identify specific cell subsets and activation markers associated with pathophysiological mechanisms and that could be used as biomarkers to discriminate both diseases. The proportion of intermediate and non-classical monocytes in the SF and PB, respectively, were significantly higher in JIA than in SA patients. In contrast the proportion of classical monocytes and their absolute numbers were higher in the SF from SA compared with JIA patients. Higher expression of CD64 on non-classical monocyte was observed in PB from SA compared with JIA patients. In SF, higher expression of CD64 on classical and intermediate monocyte as well as higher CD163 expression on intermediate monocytes was observed in SA compared with JIA patients. Moreover, whereas the number of conventional (cDC), plasmacytoid (pDC) and inflammatory (infDC) DCs was comparable between groups in PB, the number of CD141+ cDCs and CD123+ pDCs in the SF was significantly higher in JIA than in SA patients. CD14+ infDCs represented the major DC subset in the SF of both groups with potent activation assessed by high expression of HLA-DR and CD86 and significant up-regulation of HLA-DR expression in SA compared with JIA patients. Finally, higher activation of SF DC subsets was monitored in SA compared with JIA with significant up-regulation of CD86 and PDL2 expression on several DC subsets. Our results show the differential accumulation and activation of innate immune cells between septic and inflammatory arthritis. They strongly indicate that the relative high numbers of CD141+ cDC and CD123+ pDCs in SF are specific for JIA while the over-activation of DC and monocyte subsets is specific for SA.

Transient aplastic crisis triggered by parvovirus B19 in a family with hereditary spherocytosis.

Acute parvovirus B19 infection may lead to erythroblastopenia crisis in patients with underlying red blood cells disorders. We report herein an uncommon concomitant transient aplastic crisis in a mother and her daughter, both affected by hereditary spherocytosis. The diagnosis was confirmed by the detection of a very high parvovirus B19 DNA load in both the mother's and daughter's sera, associated with the presence of parvovirus B19 specific immunoglobulin-M antibodies. This rapid etiologic diagnosis allowed to save bone marrow sampling, although blood transfusion was required regarding the severe anemia associated with pancytopenia. Our observation illustrates first line parvovirus B19 hypothesis in the context of transient aplastic crisis and that contagiousness in household contacts should be considered in family with a medical history of red blood cell pathology.

Synovial-Fluid miRNA Signature for Diagnosis of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatism in childhood; microRNAs (miRNAs) have been proposed as diagnostic biomarkers. Although joints are the primary targets for JIA, a synovial fluid-based miRNA signature has never been studied. We aim to identify miRNA biomarkers in JIA by comparing synovial fluid and serum samples from children with JIA and K.kingae septic arthritis (SA). With next-generation high-throughput sequencing, we measured the absolute levels of 2083 miRNAs in synovial fluid and serum from an exploratory cohort of children and validated differentially expressed miRNAs in a replication study by using RT-qPCR. We identified a 19-miRNA signature only in synovial fluid samples that was significantly deregulated, with at least 2-fold change in expression, in JIA versus SA (p < 0.01). The combination of miR-6764-5p, miR-155, and miR-146a-5p expression in synovial fluid yielded an area under the receiver operating characteristic curve of 1 (95% CI 0.978 to 1), thereby perfectly differentiating JIA from SA in children. We propose, for the first time, a synovial fluid-specific miRNA signature for JIA and associated signaling pathways that may indicate potential biomarkers to assist in the classification and differential diagnosis of JIA and help in understanding JIA pathogenesis.

Risk factors of clinical dysimmune manifestations in a cohort of 86 children with 22q11.2 deletion syndrome: A retrospective study in France.

In this study, we describe the biological immune profiles and clinical dysimmune manifestations (infections, autoimmune diseases, and allergies) of patients with 22q11.2 deletion syndrome with the aim of determining risk factors for clinical events. This retrospective study concerned all the patients with 22q11 deletion syndrome attending the Montpellier University Hospital from January 1, 1992, to December 31, 2014 who had at least one immune investigation before the age of 18. We analyzed the clinical features, biological tests and the course of infections, autoimmunity, and allergy of 86 children. Among these 86 children, 48 (59%) had a low T lymphocyte level. Twenty-nine patients (34%) had a severe infection. The only risk factor for severe infection was the low level of CD4+ T-cells (OR: 3.3; 95% confidence interval (CI) [1.020-11.108]). Eleven patients (13%) developed an autoimmune disease; the only risk factor was an antecedent of severe infection (OR: 4.1; 95% CI [1.099-15.573]). Twenty-three patients (27%) had allergic episodes. A low level of CD8+ T-cells (OR: 3.2; 95% CI [1.07-9.409]) was significantly associated with allergy manifestations. Patients with 22q11 deletion syndrome have a high rate of dysimmune manifestations. We found statistic correlations among CD4+ T-cell count, infectious manifestations, and autoimmunity.