Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Niveau d'instruction (association avec les facteurs de risque de morbidité et la mortalité : étude d'une cohorte de 3690 sujets de quatre entreprises de la région lyonnaise)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Échappement moléculaire à la réponse immune T cytotoxique : le cas des protéines non structurales du virus de l’immunodéficience humaine et simienne

International audienc

Amylose AA

AA amyloidosis remains one of the three main types of systemic amyloidosis with AL and ATTR. Its incidence has been however decreasing recently in Western countries. Chronic inflammatory diseases are currently the first cause of AA amyloidosis, including rheumatoid arthritis, spondyloarthritis and autoinflammatory diseases. Castleman's disease is a specific cause of AA amyloidosis that can be cured by surgery. A chronic inflammatory response is required to develop amyloidosis. Other genetic and environmental factors are also involved. The first clinical manifestation is a chronic glomerular nephropathy, which can be detected by urine examination and serum creatinine measure. Immunohistochemistry is mandatory to confirm the clinical diagnosis of AA amyloidosis and to avoid misdiagnosis. Long-term prognosis remains poor on chronic dialysis in case of clinical gut involvement. Current treatment is based on the control of the inflammatory response. Specific treatment aimed at inhibiting amyloid formation targeting serum amyloid P component and heparan sulphate are currently evaluated.L’amylose AA reste l’une des trois grandes variété d’amylose multisystémique, avec l’amylose AL et les formes héréditaires. Son incidence semble toutefois diminuer dans les pays occidentaux, où les maladies inflammatoires sont la principale cause d’amylose, au premier rang desquelles se tient la polyarthrite rhumatoïde, suivie par la spondylarthrite ankylosante et les syndromes auto-inflammatoires. Parmi les tumeurs, il faut signaler la maladie de Castleman, dont l’ablation chirurgicale permet parfois la résolution des symptômes de l’amylose. Une inflammation prolongée est un prérequis au développement d’une amylose AA; la protéine majoritaire des dépôts est un fragment de la protéine serum amyloid A (SAA), l’une des protéines de la réaction inflammatoire. Cependant, d’autres facteurs, notamment génétiques, sont impliqués dans la susceptibilité à la survenue de l’amylose AA. La néphropathie est la principale manifestation clinique de l’amylose de type AA. La recherche de protéinurie et la mesure de la créatinine plasmatique restent les éléments de dépistage de l’amylose au cours de toute maladie qui comporte une inflammation chronique. Le diagnostic précis de l’amylose AA nécessite de confronter l’ensemble des données cliniques et histologiques et notamment de l’immunohistochimie, afin de ne pas la confondre avec l’une des autres variétés. Une fois installée, l’amylose AA reste de mauvais pronostic en raison de l’insuffisance rénale terminale, qui est le terme ultime de la néphropathie, et de l’atteinte digestive qui s’accompagne de dénutrition profonde. Les traitements actuels sont ciblés sur la maîtrise de l’inflammation ; des médicaments inhibant l’interaction de la protéine AA aux composants communs de l’amylose (composant amyloïde P et héparane sulfate) sont en cours d’évaluation

Familial Mediterranean Fever in Heterozygotes: Are We Able to Accurately Diagnose the Disease in Very Young Children?

International audienceObjective: Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disease due to mutations in MEFV. Descriptions of disease manifestations among patients carrying a single mutated MEFV allele are becoming more frequent, although no data are available on the long-term outcome. We undertook this study to assess the accuracy of clinical diagnosis in children carrying a single mutated MEFV allele with symptoms of recurrent autoinflammatory disorder.Methods: We performed a retrospective single-center study of 33 patients with autoinflammatory disorders age <6 years at disease onset with 1 mutated MEFV allele. The phenotype of the patients was investigated in detail, and the clinical picture and outcome of 18 patients with an initial FMF diagnosis according to current clinical criteria were compared to those of 25 homozygous or compound heterozygous FMF patients.Results: No major differences in presenting signs or initial response to colchicine were observed between patient groups. During followup, heterozygotes had a milder disease course compared to homozygotes and were less prone than homozygotes to experience new clinical signs of FMF. At puberty, clinical signs of FMF completely disappeared in 5 of 18 heterozygotes, allowing them to discontinue colchicine without recurrence of symptoms or increases in inflammatory marker levels.Conclusion: Our data suggest that the clinical diagnosis of FMF in very young heterozygous children should be made with caution. At this young age they can present with an FMF-like disease-similar to that seen in patients carrying 2 mutated alleles-that is not necessarily predictive of life-long illness

How should we approach classification of autoinflammatory diseases?

International audienceThe notion of 'autoinflammatory' disease was introduced at the end of the 1990s, and, since then, this concept has rapidly evolved. As a result, multiple definitions of autoinflammatory disease, and classifications of conditions encompassed by these definitions, have been proposed; this succession highlights advances that have been made in understanding of the innate immune system, and especially the roles of IL-1β and the inflammasome in autoinflammtory conditions. However, the definitions and classifications that have been suggested to date face a number of structure and content issues. We therefore propose another, more clinically-oriented, definition: autoinflammatory diseases are diseases with clinical signs of inflammation, associated with elevated levels of acute-phase reactants, which are attributable to dysfunction of the innate immune system, genetically-determined or triggered by an endogenous factor. From this foundation, we propose a clinically-based classification of autoinflammatory diseases, and go on to discuss how immunological diseases as a whole, including autoimmune diseases, can be appropriately located within a continuum only if the classification process is multidimensional. For this purpose, we appeal to the philosophical concepts of family resemblance and signature

076: Left atrial enlargement in sickle cell disease patients: remodelling associated with haematological parameters or index of left ventricular filling pressures

PuposeDiastolic Left ventricular (LV) dysfunction is a common finding in sickle cell disease. Furthermore, left atrial (LA) size usually reflects left ventricular filling pressures.The aim of our study was to determine if LA size is an expression of left ventricular filling pressures or reflects remodelling associated with anemia and/or haemolysis in sickle cell disease.MethodsWe evaluated 127 patients with sickle cell disease in stable condition (mean age 28,6±8,5 years, 83 women) and 38 age and sex-matched healthy controls. LA size was measured with Simpson's method in apical 4-chamber view. LV filling pressures were assessed using ratio between pulsed Doppler peak E velocity and peak Ea velocity obtained with tissue Doppler imaging of the lateral annulus (E/Ea ratio). Clinical and biologic data were collected from clinical records.ResultsCompared with the normal group, patients with sickle cell disease had a LA volume and E/Ea ratio significatively increased (48,4±11,2ml/m2; and 5,9±1,7; 30,5±7,6ml/m&sup2; and 4,5±1, respectively, p<0.0001).In multivariate analysis, LA enlargement in patients is only influenced by age and haematological parameters (haemoglobin and reticulocyte levels).No correlation was found between LA volume and E/Ea ratio (figure).ConclusionSubjects with sickle cell disease have LA enlargement. However, in this population, LA dilatation is not an index of left ventricular filling pressures.Figur

Dramatic beneficial effect of interleukin-1 inhibitor treatment in patients with familial Mediterranean fever complicated with amyloidosis and renal failure

Background. Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder, for which systemic AA amyloidosis is the major complication revealed most of the time by renal abnormalities. Current treatment is daily colchicine that prevents both recurrent inflammatory attacks and amyloidosis deposition in most patients. However, some patients still develop amyloidosis and renal failure. Functional studies suggest that interleukin (IL)-1 is implicated in the inflammatory reaction in FMF and therefore, IL-1 inhibitors could be a new approach to treat FMF. The aim of this series study was to evaluate anakinra in patients with FMF complicated with amyloidosis and renal failure