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  • 1
    In: Rheumatology, 2017, Vol. 56(suppl2)
    ISSN: 1462-0324
    E-ISSN: 1462-0332
    Source: Oxford University Press
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  • 2
    In: Rheumatology, 2018, Vol. 57(suppl3)
    Keywords: Medicine;
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 3
    In: Rheumatology, 2013, Vol. 52(suppl1), pp.i8-i17
    Description: Historically immunology was considered to be the science of self–non-self discrimination and inflammation against self was invariably considered in relationship to B and T cell tolerance failure. Indeed the classical autoantibody associated autoimmunity paradigm, that sometimes powerfully manifests as fulminant lupus-related thrombosis, for example, attests to the veracity of the autoimmunity concept that underpins much of rheumatology practice. However, non-infectious inflammation against self was suspected not to be exclusively within the realms of autoimmunity, but until recently a clearly defined concept of what exactly this represented did not exist. The teaching of immunology commences with the fact that the immune system is composed of an innate and an adaptive arm and that these are ultimately functionally integrated. Over a decade ago the word autoinflammation was used to describe rare monogenic disorders including familial mediterranean fever (FMF) and TNF-associated peroidic fever syndrome (TRAPS) where the inflammation was not onstensibly linked to autoimmunity. Recognizing that perturbation of immune responses could equally be dependent on aberrant innate immunity we defined autoinflammmation as the diametric opposite boundary to autoimmunity where disease is driven by intrinsic perturbation of the non-immune cells of the target tissues or the innate immune populations that patrol these sites [1]. The innate immune-dependent or autoinflammatory disorders have clinical phenotypes distinct from those of autoimmunity and at the molecular level often converge on key cytokines such as IL-1 or TNF. The purpose of this talk is to show how autoinflammation can be recognized based on clinical features, serology and genetics. It also shows how diseases that were formerly designated as autoimmune may in some cases be autoinflammatory at disease inception. Diseases that are intermediate between autoinflammation and autoimmunity will be briefly touched on. The proper clinical designate of autoinflammation is key for treatment strategies. Thus far, many of the autoinflammatory diseases have shown a remarkable response to strategies of IL-1 antagonism. Illustrative cases including those where a clear diagnosis was not initially evident will be used to show treatment strategies.     1. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006;3:e297.
    Keywords: Medicine;
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 4
    Language: English
    In: Arthritis & Rheumatism, February 2010, Vol.62(2), pp.312-315
    Keywords: Arthritis, Rheumatoid ; Magnetic Resonance Imaging ; Synovitis ; X-Ray Microtomography;
    ISSN: 0004-3591
    E-ISSN: 1529-0131
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  • 5
    In: Rheumatology, 2017, Vol. 56(suppl2)
    Keywords: Medicine;
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 6
    Language: English
    In: The Journal of Allergy and Clinical Immunology, May 2018, Vol.141(5), pp.1953-1953
    Keywords: Medicine
    ISSN: 0091-6749
    E-ISSN: 1097-6825
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  • 7
    Language: English
    In: Annals of the Rheumatic Diseases, 27 April 2016, Vol.75(4), p.e17
    Description: We thank Yang et al1 for their comments on our whole body MRI study in patients with polymyalgia rheumatica (PMR). Our previous work in PMR revealed inflammatory changes outside the joint cavity, or ‘extracapsular pattern disease’, in both the shoulder and the hand.2 3 In a preliminary analysis of four non-contrast whole-body MRIs in the present cohort, we saw an identical pattern of disease in PMR and consequently developed the scoring system described. In addition to scoring the individual sites semi-quantitatively, we also classified the overall pattern as ‘extracapsular’ or not, using visual pattern recognition. This Gestalt-based classification was not derived directly from any of the individual site scores.
    Keywords: Polymyalgia Rheumatica ; Inflammation ; Rheumatoid Arthritis
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 8
    Language: English
    In: Rheumatology (Oxford, England), September 2015, Vol.54(9), pp.1539-40
    Description: The aim of this study was to evaluate the construct validity of enthesis US in the assessment of disease activity in SpA.
    Keywords: Severity of Illness Index ; Achilles Tendon -- Diagnostic Imaging ; Spondylarthritis -- Diagnosis ; Ultrasonography, Doppler -- Methods
    ISSN: 14620324
    E-ISSN: 1462-0332
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  • 9
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 28 March 2017, Vol.114(13), pp.E2748-E2757
    Description: The proinflammatory cytokine IL-36γ is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36γ is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36γ is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36γ activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36γ-activating protease expressed by epithelial cells. Interestingly, cathepsin S activity was strongly up-regulated in samples extracted from psoriasis patients relative to healthy controls. In addition, IL-36γ-Ser18, identified as the main product of cathepsin S-dependent IL-36γ cleavage, induced psoriasiform changes in human skin-equivalent models. Together, these data provide important mechanistic insights into the activation of IL-36γ and highlight that cathepsin S-mediated activation of IL-36γ may be important in the development of numerous IL-36γ-driven pathologies, in addition to psoriasis.
    Keywords: Il-1 ; Il-36 ; Cytokine ; Inflammation ; Psoriasis ; Cathepsins -- Metabolism ; Interleukin-1 -- Genetics ; Psoriasis -- Genetics
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 10
    In: PLoS ONE, 2015, Vol.10(3)
    Description: Introduction Current clinical trials utilize mesenchymal stromal cells (MSCs) expanded in culture, however these interventions carry considerable costs and concerns pertaining to culture-induced losses of potency. This study assessed the feasibility of new clinical-grade technology to obtain uncultured MSC isolates from three human intra-osseous tissue sources based on immunomagnetic selection for CD271-positive cells. Materials and Methods MSCs were isolated from bone marrow (BM) aspirates or surgical waste materials; enzymatically digested femoral heads (FHs) and reamer irrigator aspirator (RIA) waste fluids. Flow cytometry for the CD45 −/low CD73 + CD271 + phenotype was used to evaluate uncultured MSCs before and after selection, and to measure MSC enrichment in parallel to colony forming-unit fibroblast assay. Trilineage differentiation assays and quantitative polymerase chain-reaction for key transcripts involved in bone regeneration was used to assess the functional utility of isolated cells for bone repair. Results Uncultured CD45 −/low CD271 + MSCs uniformly expressed CD73, CD90 and CD105 but showed variable expression of MSCA-1 and SUSD2 (BM〉RIA〉FH). MSCs were enriched over 150-fold from BM aspirates and RIA fluids, whereas the highest MSC purities were obtained from FH digests. Enriched fractions expressed increased levels of BMP-2, COL1A2, VEGFC, SPARC and CXCL12 transcripts (BM〉RIA〉FH), with the highest up-regulation detected for CXCL12 in BM (〉1300-fold). Following culture expansion, CD271-selected MSCS were tri-potential and phenotypically identical to plastic adherence-selected MSCs. Discussion A CD271-based GMP-compliant immunomagnetic selection resulted in a substantial increase in MSC purity and elevated expression of transcripts involved in bone formation, vascularisation and chemo-attraction. Although this technology, particularly from RIA fluids, can be immediately applied by orthopaedic surgeons as autologous therapy, further improvements in MSC purities and pre-clinical testing of product safety would be required to develop this process for allogeneic applications.
    Keywords: Research Article
    E-ISSN: 1932-6203
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