Potential role of IFNα in adult lupus

Patients with lupus have a continuous production of IFNα and display an increased expression of IFNα-regulated genes. The reason for the ongoing IFNα synthesis in these patients seems to be an activation of plasmacytoid dendritic cells (pDCs) by immune complexes (ICs), consisting of autoantibodies in combination with DNA-containing or RNA-containing autoantigens. The mechanisms behind the activation of pDCs by such ICs have to some extent been elucidated during the last years. Thus, interferogenic ICs are internalized via the FcγRIIa expressed on pDCs, reach the endosomes and stimulate Toll-like receptor (TLR) 7 or 9, which subsequently leads to IFNα gene transcription. Variants of genes involved in both the IFNα synthesis and response have been linked to an increased risk to develop lupus. Among these genes are interferon regulatory factor 5 (IRF5), which is involved in TLR signaling, and the signal transducer and activator of transcription 4 (STAT4) that interacts with the type I interferon receptor. Produced IFNα may at least partially be responsible for several of the observed alterations in the immune system of lupus patients and contribute to the autoimmune disease process, which will be discussed in the present review. How produced IFNα can contribute to some clinical manifestations will briefly be described, as well as the possible consequences of this knowledge in clinical practice for disease monitoring and therap

Entrepreneurship and Gender Equality in Academia – a Complex Combination in Practice

This article takes as its starting point two current trends in academia – the promotion of academic entrepreneurship and innovation and the promotion of gender equality – and discusses how different gender equality perspectives are interwoven, or not, into academia’s transformation processes towards entrepreneurial universities. On the basis of an analysis of 26 interviews conducted with personnel at two Swedish universities, the article investigates how concepts of academic entrepreneurship and innovation on the one hand and gender equality on the other hand are constructed and filled with meaning as well as how they are entangled and what effects are produced by this way of thinking and acting. Our analysis reveals tensions between the two policy goals, together with tensions within each goal. An overall conclusion is that articulations and ways of speaking about the policy goal of academic entrepreneurship and innovation were to some extent interwoven with the policy goal of gender equality, especially in the broader perspectives on academic entrepreneurship. However, the articulations of strategies and practice of the two policy goals essentially ran parallel, and were not entangled with one another. This is because strategies or substantial initiatives for merging gender equality into the agenda of academic entrepreneurship and innovation were lacking

Det fulländade livet/den naiva konsumenten? – En kvalitativ innehållsanalys av arbetsporträtteringen i livsstilstidningar

Denna uppsats diskuterar ett nytt begrepp som inte många är bekanta vid, men som vi alla är en del av: slash-karriärer. En slash-karriär kan sägas vara ett uttryck för vår syn på ett arbete idag och alla de etablerade värderingar och ideal som ligger bakom. För att undersöka vilka dessa ideal och föreställningar är och vad de säger om vår syn på en karriär idag har jag, genom att utföra en kvalitativ innehållsanalys, studerat hur livsstilstidningar porträtterar en lycklig och framgångsrik karriär idag. Detta blir mitt syfte i uppsatsen. I tidningarna kunde jag urskilja tre teman: en uppmaning till att kämpa och ge allt för att kunna nå sina personliga mål, att våga ta chanserna som presenterar sig oavsett medföljande risker samt ett individualistiskt tänk som präglar alla artiklarna. Dessa analyserades och det kan konkluderas att individen har fått ökad frihet som måste användas till att förändra sitt liv och söka nå sina drömmar och begär, vilka individen själv ansvarar för. Detta leder till en osäkerhet som konsumtionsmarknaden utnyttjar. Marknaden lurar individer till att tro att de behöver deras redskap för att kunna marknadsföra sig själva och på så sätt nå en attraktiv karriär. Genom att underhålla begären och samtidigt lova individer lycka i varje sekund skapar de ständigt nya behov vilket innebär att människorna själva är med och befrämjar konsumtionssamhället. Människan kan på så sätt inte undvika uppbyggnaden av systemet utan måste konsumera, annars blir hon utestängd ifrån samhället. Idealet i samhället är att inneha en elitplats och arbeta med ett slash-yrke inom mode-eller media. Målet är att inte känna att man jobbar eller har fritid, vilket innebär att individen når fullständig tillfredsställelse. Dock tenderar verkliga erfarenheter inte resultera i samma positiva liv som tidningarna hävdar. Livsstilstidningarna porträtterar en slags fantasivärld och utopi som inte alls stämmer överrens med verkliga livet. Utan om vi följer deras tips kommer vi istället att uppleva osäkerhet och otrygghet samt ofta misslyckas vilket leder till sämre ekonomi och psykisk ohälsa

Clinical Features and Risk Factors of Autoimmune Liver Involvement in Pediatric Inflammatory Bowel Disease

OBJECTIVES:Autoimmune liver disease is reported in up to 7.8% of children with inflammatory bowel disease. A distinct inflammatory bowel disease phenotype has been suggested in adults and in small pediatric cohorts. The aim of the study was to evaluate the features of inflammatory bowel disease associated with autoimmune liver diseases and to analyze the characteristics of the liver disease. METHODS:Information on patients was obtained from the Italian Pediatric Inflammatory Bowel Disease Registry. Data of patients with and without autoimmune liver disease were compared. RESULTS:Autoimmune liver disease was detected in 6.8% of the 677 patients enrolled and was significantly associated with the diagnosis of ulcerative colitis (83%), with pancolonic involvement (84%), and with perinuclear antineutrophil cytoplasmic antibody positivity (41%) (all Ps < 0.05). Autoimmune liver disease was defined as sclerosing cholangitis in 61% of the patients and as an overlap syndrome in 33%. Concomitant intra- and extrahepatic biliary involvement was reported in 61% of cases, whereas exclusive extrahepatic lesions were reported in 21%. Hepatobiliary complications were observed in 9% of the patients during follow-up. CONCLUSIONS:Autoimmune liver disease, especially sclerosing cholangitis, was significantly more common in patients with extensive ulcerative colitis. Although complications are relatively rare in the pediatric age, monitoring is recommended

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

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Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases

Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), and rheumatoid arthritis (RA) are chronic inflammatory diseases in which abnormalities of B cell function play a central role. Although it is widely accepted that autoimmune B cells are hyperactive in vivo, a full understanding of their functional status in AID has not been delineated. Here, we present a detailed analysis of the functional capabilities of AID B cells and dissect the mechanisms underlying altered B cell function. Upon BCR activation, decreased spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk) phosphorylation was noted in AID memory B cells combined with constitutive co-localization of CD22 and protein tyrosine phosphatase (PTP) non-receptor type 6 (SHP-1) along with hyporesponsiveness to TLR9 signaling, a Syk-dependent response. Similar BCR hyporesponsiveness was also noted specifically in SLE CD27- B cells together with increased PTP activities and increased transcripts for PTPN2, PTPN11, PTPN22, PTPRC, and PTPRO in SLE B cells. Additional studies revealed that repetitive BCR stimulation of normal B cells can induce BCR hyporesponsiveness and that tissue-resident memory B cells from AID patients also exhibited decreased responsiveness immediately ex vivo, suggesting that the hyporesponsive status can be acquired by repeated exposure to autoantigen(s) in vivo. Functional studies to overcome B cell hyporesponsiveness revealed that CD40 co-stimulation increased BCR signaling, induced proliferation, and downregulated PTP expression (PTPN2, PTPN22, and receptor-type PTPs). The data support the conclusion that hyporesponsiveness of AID and especially SLE B cells results from chronic in vivo stimulation through the BCR without T cell help mediated by CD40-CD154 interaction and is manifested by decreased phosphorylation of BCR-related proximal signaling molecules and increased PTPs. The hyporesponsiveness of AID B cells is similar to a form of functional anergy