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Mashup Score: 48Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases - 16 day(s) ago
Due to optimised treatment strategies and the availability of new therapies during the last decades, formerly devastating chronic inflammatory diseases such as rheumatoid arthritis or systemic sclerosis (SSc) have become less menacing. However, in many patients, even state-of-the-art treatment cannot induce remission. Moreover, the risk for flares strongly increases once anti-inflammatory therapy is tapered or withdrawn, suggesting that underlying pathological processes remain active even in the absence of overt inflammation. It has become evident that tissues have the ability to remember past encounters with pathogens, wounds and other irritants, and to react more strongly and/or persistently to the next occurrence. This priming of the tissue bears a paramount role in defence from microbes, but on the other hand drives inflammatory pathologies (the Dr Jekyll and Mr Hyde aspect of tissue adaptation). Emerging evidence suggests that long-lived tissue-resident cells, such as fibroblasts,
Source: ard.bmj.comCategories: General Medicine News, RheumatologyTweet
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Mashup Score: 23Disease flares with baricitinib dose reductions and development of flare criteria in patients with CANDLE/PRAAS - 17 day(s) ago
Objectives Patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS) respond to the janus kinase inhibitor 1/2 inhibition with baricitinib at exposures higher than in rheumatoid arthritis. Baricitinib dose reductions to minimise exposure triggered disease flares which we used to develop ‘flare criteria’. Methods Of 10 patients with CANDLE/PRAAS treated with baricitinib in an open-label expanded-access programme, baricitinib doses were reduced 14 times in 9 patients between April 2014 and December 2019. Retrospective data analysis of daily diary scores and laboratory markers collected before and after the dose reductions were used to develop ‘clinical’ and ‘subclinical’ flare criteria. Disease flare rates were compared among patients with 25% dose reductions and during study visits when patients received recommended ‘optimized’ baricitinib doses (high-dose visits) versus low
Source: ard.bmj.comCategories: General Medicine News, RheumatologyTweet
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Mashup Score: 27
Emerging evidence points to the involvement of periodontal disease (PD) in the pathogenesis of rheumatoid arthritis (RA), especially in anti-citrullinated protein antibodies (ACPA)-positive RA. The bacteria Porphyromonas gingivalis , involved in oral mucosal inflammation and PD, can citrullinate proteins via prokaryotic peptidylarginine deiminase.1 Systemic translocation of oral bacteria has been found in RA-patients with PD. These bacterial translocations have been implicated in the generation of anti-modified protein antibodies (AMPAs) as ACPA can also recognise modified bacterial proteins.2 Nevertheless, the ‘cause-consequence’ relation between PD and RA remains debatable as PD may be a risk factor (PD→RA; scenario 1; figure 1A) but also a consequence of RA (RA→PD; scenario 2).3 Additionally, the relation PD→RA may be confounded by related factors (eg, body mass index (BMI), smoking or other factors related to socioeconomic status (SES); scenario 3). Increased prevalence of periodon
Source: ard.bmj.comCategories: General Medicine News, RheumatologyTweet
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Mashup Score: 104Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc) - 19 day(s) ago
Objectives In the complex panorama of autoimmune diseases, the characterisation of pivotal contributing autoantibodies that are involved in disease progression remains challenging. This study aimed to employ a global antibody profiling strategy to identify novel antibodies and investigate their association with systemic sclerosis (SSc). Methods We implemented this strategy by conducting immunoprecipitation (IP) following on-bead digestion with the sera of patients with SSc or healthy donors, using antigen pools derived from cell lysates. The enriched antigen-antibody complex was proceeded with mass spectrometry (MS)-based quantitative proteomics and over-represented by bioinformatics analysis. The candidate antibodies were then orthogonally validated in two independent groups of patients with SSc. Mice were immunised with the target antigen, which was subsequently evaluated by histological examination and RNA sequencing. Results The IP-MS analysis, followed by validation in patients wi
Source: ard.bmj.comCategories: General Medicine News, RheumatologyTweet
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Mashup Score: 49
Giant cell arteritis (GCA), the most common systemic vasculitis, is characterised by aberrant interactions between infiltrating and resident cells of the vessel wall. Ageing and breach of tolerance are prerequisites for GCA development, resulting in dendritic and T-cell dysfunction. Inflammatory cytokines polarise T-cells, activate resident macrophages and synergistically enhance vascular inflammation, providing a loop of autoreactivity. These events originate in the adventitia, commonly regarded as the biological epicentre of the vessel wall, with additional recruitment of cells that infiltrate and migrate towards the intima. Thus, GCA-vessels exhibit infiltrates across the vascular layers, with various cytokines and growth factors amplifying the pathogenic process. These events activate ineffective repair mechanisms, where dysfunctional vascular smooth muscle cells and fibroblasts phenotypically shift along their lineage and colonise the intima. While high-dose glucocorticoids broadl
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Mashup Score: 22
Introduction AA amyloidosis (AA) can be the consequence of any chronic inflammatory disease. AA is associated with chronic inflammatory diseases (cid+AA), autoinflammatory syndromes (auto+AA) or AA of unknown origin or idiopathic AA (idio+AA). The major organ manifestation is renal AA that can progress to end-stage renal disease (ESRD) and multiple organ failure. Materials and methods This study is a monocentric retrospective analysis of the renal outcome and survival of patients with cid+AA (n=34), auto+AA (n=24) and idio+AA (n=25) who were treated with cytokine-inhibiting biological disease-modifying antirheumatic drugs (bDMARDs). Results 83 patients with renal AA were identified and followed for a mean observational period of 4.82 years. C reactive protein (CRP), serum amyloid alpha and proteinuria were significantly reduced with bDMARD therapy. Progression to ESRD was prevented in 60% (cid+AA), 88% (auto+AA) and 81% (idio+AA) of patients. Tocilizumab was given to 34 patients with c
Source: ard.bmj.comCategories: General Medicine News, RheumatologyTweet
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Mashup Score: 34Disease flares with baricitinib dose reductions and development of flare criteria in patients with CANDLE/PRAAS - 25 day(s) ago
Objectives Patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS) respond to the janus kinase inhibitor 1/2 inhibition with baricitinib at exposures higher than in rheumatoid arthritis. Baricitinib dose reductions to minimise exposure triggered disease flares which we used to develop ‘flare criteria’. Methods Of 10 patients with CANDLE/PRAAS treated with baricitinib in an open-label expanded-access programme, baricitinib doses were reduced 14 times in 9 patients between April 2014 and December 2019. Retrospective data analysis of daily diary scores and laboratory markers collected before and after the dose reductions were used to develop ‘clinical’ and ‘subclinical’ flare criteria. Disease flare rates were compared among patients with 25% dose reductions and during study visits when patients received recommended ‘optimized’ baricitinib doses (high-dose visits) versus low
Source: ard.bmj.comCategories: General Medicine News, RheumatologyTweet
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Mashup Score: 11What rheumatologists need to know about mRNA vaccines: current status and future of mRNA vaccines in autoimmune inflammatory rheumatic diseases - 26 day(s) ago
Messenger RNA (mRNA) vaccines as a novel vaccine platform offer new tools to effectively combat both emerging and existing pathogens which were previously not possible. The ‘plug and play’ feature of mRNA vaccines enables swift design and production of vaccines targeting complex antigens and rapid incorporation of new vaccine constituents as needed. This feature makes them likely to be adopted for widespread clinical use in the future. Currently approved mRNA vaccines include only those against SARS-CoV-2 virus. These vaccines demonstrate robust immunogenicity and offer substantial protection against severe disease. Numerous mRNA vaccines against viral pathogens are in the early to late phase of development. Several mRNA vaccines for influenza are tested in clinical trials, with some already in phase 3 studies. Other vaccines in the early and late phases of development include those targeting Cytomegalovirus , varicella zoster virus, respiratory syncytial virus and Epstein-Barr virus.
Source: ard.bmj.comCategories: General Medicine News, RheumatologyTweet
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Mashup Score: 10Disease activity drives divergent epigenetic and transcriptomic reprogramming of monocyte subpopulations in systemic lupus erythematosus - 27 day(s) ago
Objectives Systemic lupus erythematosus (SLE) is characterised by systemic inflammation involving various immune cell types. Monocytes, pivotal in promoting and regulating inflammation in SLE, differentiate from classic monocytes into intermediate and non-classic monocytes, assuming diverse roles and changing their proportions in inflammation. In this study, we investigated the epigenetic and transcriptomic profiles of these and novel monocyte subsets in SLE in relation to activity and progression. Methods We obtained the DNA methylomes and transcriptomes of classic, intermediate, non-classic monocytes in patients with SLE (at first and follow-up visits) and healthy donors. We integrated these data with single-cell transcriptomics of SLE and healthy donors and interrogated their relationships with activity and progression. Results In addition to shared DNA methylation and transcriptomic alterations associated with a strong interferon signature, we identified monocyte subset-specific al
Source: ard.bmj.comCategories: General Medicine News, Future of MedicineTweet
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Mashup Score: 40Interrupting an IFN-γ-dependent feedback loop in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne - 28 day(s) ago
Objectives To study the molecular pathogenesis of PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome, a debilitating hereditary autoinflammatory disease caused by dominant mutation in PSTPIP1 . Methods Gene knock-out and knock-in mice were generated to develop an animal model. THP1 and retrovirally transduced U937 human myeloid leukaemia cell lines, peripheral blood mononuclear cells, small interfering RNA (siRNA) knock-down, site-directed mutagenesis, cytokine immunoassays, coimmunoprecipitation and immunoblotting were used to study inflammasome activation. Cytokine levels in the skin were evaluated by immunohistochemistry. Responsiveness to Janus kinase (JAK) inhibitors was evaluated ex vivo with peripheral blood mononuclear cells and in vivo in five treatment-refractory PAPA patients. Results The knock-in mouse model of PAPA did not recapitulate the human disease. In a human myeloid cell line model, PAPA-associated PSTPIP1 mutations activated the pyrin inflammasome, b
Source: ard.bmj.comCategories: General Medicine News, RheumatologyTweet
🤩 A must-read review on inflammatory tissue #priming 🔥 🔎 "Dr Jekyll and Mr Hyde aspect" of tissue #adaptation 💭 Tissues remember past encounters with non-self 💥 Priming drives inflammatory pathologies 👉 promising treatments in #RA & #SSc 🔗 https://t.co/YqP9SrgEr5 https://t.co/jR5NPN35xY