La pratique du peau à peau chez les grands prématurés (Expérience dans un service de réanimation néonatale au CHU de Strasbourg. Etude prospective.)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

Quality of life in monogenic autoinflammatory diseases. A review

International audienc

Efficacy of JAK1/2 inhibition in the treatment of chilblain lupus due to TREX1 deficiency

LetterInternational audienceThe type I interferonopathies, Mendelian disorders characterised by constitutive upregulation of the type I interferon (IFN) pathway, are associated with a spectrum of phenotypes particularly involving the brain and the skin.1 Mutations in the 3′−5′ DNA exonuclease TREX1 were the first described cause of the severe encephalopathy Aicardi-Goutières syndrome (AGS),2 of which acral vasculitic lesions are a well-recognised feature [...

Efficacy of JAK1/2 inhibition in the treatment of chilblain lupus due to TREX1 deficiency

LetterInternational audienceThe type I interferonopathies, Mendelian disorders characterised by constitutive upregulation of the type I interferon (IFN) pathway, are associated with a spectrum of phenotypes particularly involving the brain and the skin.1 Mutations in the 3′−5′ DNA exonuclease TREX1 were the first described cause of the severe encephalopathy Aicardi-Goutières syndrome (AGS),2 of which acral vasculitic lesions are a well-recognised feature [...

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

International audienceDespite 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

Synovial-Fluid miRNA Signature for Diagnosis of Juvenile Idiopathic Arthritis

International audienceJuvenile 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

Familial and syndromic lupus share the same phenotype as other early-onset forms of lupus.

International audienceStudies of early-onset systemic lupus erythematosus (SLE) have identified monogenic forms of the disease. The primary objective of this study was to compare the clinical and laboratory features of the first patients included in the GENIAL/LUMUGENE cohort to those reported in previous publications. The secondary objective was to determine whether subgroups with a distinctive pattern of clinical and biological features are seen in predominantly genetic forms of SLE

Contribution of rare and predicted pathogenic gene variants to childhood-onset lupus: a large, genetic panel analysis of British and French cohorts

International audienceBackgroundSystemic lupus erythematosus (SLE) is a rare immunological disorder and genetic factors are considered important in its causation. Monogenic lupus has been associated with around 30 genotypes in humans and 60 in mice, while genome-wide association studies have identified more than 90 risk loci. We aimed to analyse the contribution of rare and predicted pathogenic gene variants in a population of unselected cases of childhood-onset SLE.MethodsFor this genetic panel analysis we designed a next-generation sequencing panel comprising 147 genes, including all known lupus-causing genes in humans, and potentially lupus-causing genes identified through GWAS and animal models. We screened 117 probands fulfilling American College of Rheumatology (ACR) criteria for SLE, ascertained through British and French cohorts of childhood-onset SLE, and compared these data with those of 791 ethnically matched controls from the 1000 Genomes Project and 574 controls from the FREX Consortium.FindingsAfter filtering, mendelian genotypes were confirmed in eight probands, involving variants in C1QA, C1QC, C2, DNASE1L3, and IKZF1. Seven additional patients carried heterozygous variants in complement or type I interferon-associated autosomal recessive genes, with decreased concentrations of the encoded proteins C3 and C9 recorded in two patients. Rare variants that were predicted to be damaging were significantly enriched in the childhood-onset SLE cohort compared with controls; 25% of SLE probands versus 5% of controls were identified to harbour at least one rare, predicted damaging variant (p=2·98 × 10 −11). Inborn errors of immunity were estimated to account for 7% of cases of childhood-onset SLE, with defects in innate immunity representing the main monogenic contribution.InterpretationAn accumulation of rare variants that are predicted to be damaging in SLE-associated genes might contribute to disease expression and clinical heterogeneity

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD