Soluble markers of B cell activation suggest a role of B cells in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension

IntroductionSoluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease characteristics.Methods1. Serum levels of 14 B cell biomarkers (β2-microglobulin, rheumatoid factor (RF), immunoglobulins (Ig) G, IgA, IgM, BAFF, APRIL, soluble (s)TACI, sBCMA sCD21, sCD23, sCD25, sCD27, CXCL13) were measured in SSc patients and healthy controls (HC). 2. Associations between these biomarkers and SSc characteristics were assessed. 3. The pathophysiological relevance of identified associations was explored by studying protein production in B cell culture supernatant.ResultsIn a discovery panel of 80 SSc patients encompassing the broad spectrum of disease manifestations, we observed a higher frequency of RF positivity, and increased levels of β2-microglobulin, IgG and CXCL13 compared with HC. We found significant associations between several biomarkers and SSc characteristics related to disease phenotype, activity and severity. Especially, serum IgG levels were associated with pulmonary hypertension (PH); β2-microglobulin with Nt-pro-BNP and DLCO; and BAFF with peak tricuspid regurgitation velocity (TRV). In a validation cohort of limited cutaneous SSc patients without extensive ILD, we observed lower serum IgG levels, and higher β2-microglobulin, sBCMA, sCD23 and sCD27 levels in patients with pulmonary arterial hypertension (PAH). BAFF levels strongly correlated with Nt-pro-BNP levels, FVC/DLCO ratio and peak TRV in SSc-PAH patients. Cultured SSc B cells showed increased production of various angiogenic factors (angiogenin, angiopoietin-1, VEGFR-1, PDGF-AA, MMP-8, TIMP-1, L-selectin) and decreased production of angiopoietin-2 compared to HC.ConclusionSoluble markers of B cell activation could be relevant tools to assess organ involvements, activity and severity in SSc. Their associations with PAH could plead for a role of B cell activation in the pathogenesis of pulmonary microangiopathy. B cells may contribute to SSc vasculopathy through production of angiogenic mediators

Étonnants historiens : les lointaines fabriques de l'histoire 1/2

Une demi-journée exceptionnelle autour de l'"Encyclopédie des historiographies : Afriques, Amériques, Asie", premier volet d'une aventure éditoriale novatrice s'intéressant à l'écriture de l'histoire à toutes les époques et dans (presque) toutes les parties du monde

Simple gene signature to assess murine fibroblast polarization

International audienceAbstract We provide an original multi-stage approach identifying a gene signature to assess murine fibroblast polarization. Prototypic polarizations (inflammatory/fibrotic) were induced by seeded mouse embryonic fibroblasts (MEFs) with TNFα or TGFß1, respectively. The transcriptomic and proteomic profiles were obtained by RNA microarray and LC-MS/MS. Gene Ontology and pathways analysis were performed among the differentially expressed genes (DEGs) and proteins (DEPs). Balb/c mice underwent daily intradermal injections of HOCl (or PBS) as an experimental murine model of inflammation-mediated fibrosis in a time-dependent manner. As results, 1456 and 2215 DEGs, and 289 and 233 DEPs were respectively found in MEFs in response to TNFα or TGFß1, respectively . Among the most significant pathways, we combined 26 representative genes to encompass the proinflammatory and profibrotic polarizations of fibroblasts. Based on principal component analysis, this signature deciphered baseline state, proinflammatory polarization, and profibrotic polarization as accurately as RNA microarray and LC-MS/MS did. Then, we assessed the gene signature on dermal fibroblasts isolated from the experimental murine model. We observed a proinflammatory polarization at day 7, and a mixture of a proinflammatory and profibrotic polarizations at day 42 in line with histological findings. Our approach provides a small-size and convenient gene signature to assess murine fibroblast polarization

Encyclopédie des historiographies : Afriques, Amériques, Asies

Quels rapports les sociétés humaines entretiennent-elles avec leur passé et quels récits font-elles du temps révolu ? Pour ce premier volume de l’Encyclopédie des historiographies. Afriques, Amériques, Asies, 157 spécialistes représentant 88 institutions académiques en France et dans le monde explorent l’univers des productions humaines qui constituent des sources pour l’historien et déchiffrent les nombreuses modalités (« scientifiques », littéraires, artistiques, monumentales…) de l’écriture du passé. Évoquant tour à tour l’Afrique, l’Amérique latine, l’Asie, l’Océanie, les 216 notices de l’ouvrage présentent des matériaux historiques de toute nature, issus de toutes les époques, souvent méconnus, ainsi que l’histoire de leurs usages. L’entreprise collective qu’est l’Encyclopédie se veut novatrice : il s’agit de susciter une réflexion historiographique résolument non-occidentalo-centrée qui complète utilement les démarches épistémologiques traditionnelles. Nouvel outil de connaissance historique forgé à l’heure de la mondialisation, l’Encyclopédie des historiographies est aussi une véritable invitation au voyage.What are the different types of relations that non-Western societies upkeep with their past and how are narratives about the past produced by them? In this first volume of the Encyclopaedia of Historiography: Africa, America, Asia, 157 specialists from 88 international academic institutions explore the wealth of evidence that constitutes source material for historians. They also examine the immensely diverse modes or genres of narrated history: “scientific”, literary, artistic, architectural, etc. 216 entries dealing with Africa, Latin America, Oceania, and Asia, cover a large variety of sources, including many which are unfamiliar to the Western or non-Western reader, along with the history of how they have been exploited. By bringing together for the first time such an abundance of material the reader is offered the possibility of exploring continents and building meaningful connections across space and time. In addition to being a new tool for historical enquiry in an era of globalization, this encyclopaedia is also an invitation to travel the world