106 research outputs found
Henri Temianka Correspondence; (humby)
No full textThis collection contains material pertaining to the life, career, and activities of Henri Temianka, violin virtuoso, conductor, music teacher, and author. Materials include correspondence, concert programs and flyers, music scores, photographs, and books.https://digitalcommons.chapman.edu/temianka_correspondence/3632/thumbnail.jp
Editorial: Synovial tissue: turning the page to precision medicine in arthritis?
No full textCopyright © 2021 Orr, Humby and Fonseca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.It is with great pleasure that we present in this article collection, a timely overview of the rapidly developing field of synovial tissue analysis. Some of the most prominent protagonists in the field have contributed, and the collection walks the reader through everything from the history of the field’s development, to technical aspects of sampling, providing an update on the science and clinical applications, as well as discussing potential future perspectives. A broad consensus exists amongst clinicians and scientists, that a patient-centred, precision medicine approach holds the most promise to improve patient outcomes. The relevance of synovial biopsies in achieving this end is a major theme of this article collection. We are currently at an exciting juncture in this important field. This collection not only discusses the enormous potential of synovial tissue as a research and clinical tool, but also the many challenges in advancing its role in translational and clinical applications. Several key advancements concerning synovial biopsies over the last number of years have together contributed to the rheumatology community discussing in earnest how such sampling can contribute to precision medicine in arthritis.info:eu-repo/semantics/publishedVersio
Can Synovial Pathobiology Integrate with Current Clinical and Imaging Prediction Models to Achieve Personalized Health Care in Rheumatoid Arthritis?
No full textAlthough great progress has been made in the past decade toward understanding the pathogenesis of rheumatoid arthritis (RA), clinicians remain some distance from a goal of personalized health care. The capacity to diagnose RA early, predict prognosis, and moreover predict response to biologic therapies has been a research focus for many years. How currently available clinical prediction models can facilitate such goals is reviewed in this article. In addition, the role of current imaging techniques in this regard is also discussed. Finally, the authors review the current literature regarding synovial biomarkers and consider whether integration of synovial pathobiology into clinical prediction algorithms may enhance their predictive value
Ectopic Lymphoid Structures Support Ongoing Production of Class-Switched Autoantibodies in Rheumatoid Synovium
No full textBackgroundFollicular structures resembling germinal centres (GCs) that are characterized by follicular dendritic cell (FDC) networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA). However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i) express activation-induced cytidine deaminase (AID), the enzyme required for somatic hypermutation and class-switch recombination (CSR) of Ig genes; (ii) support ongoing CSR and ACPA production; and (iii) remain functional in a RA/severe combined immunodeficiency (SCID) chimera model devoid of new immune cell influx into the synovium.Methods and findingsUsing immunohistochemistry (IHC) and quantitative Taqman real-time PCR (QT-PCR) in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching) was observed in synovial grafts expressing FDCs/CD21L. Furthermore, synovial mRNA levels of AID were closely associated with circulating human IgG ACPA in mouse sera. Finally, the survival and proliferation of functional B cell niches was associated with persistent overexpression of genes regulating ectopic lymphoneogenesis.ConclusionsOur demonstration that FDC+ follicular units invariably express AID and are surrounded by ACPA-producing plasma cells provides strong evidence that ectopic lymphoid structures in the RA synovium are functional and support autoantibody production. This concept is further confirmed by evidence of sustained AID expression, B cell proliferation, ongoing CSR, and production of human IgG ACPA from GC+ synovial tissue transplanted into SCID mice, independently of new B cell influx from the systemic circulation. These data identify AID as a potential therapeutic target in RA and suggest that survival of functional synovial B cell niches may profoundly influence chronic inflammation, autoimmunity, and response to B cell-depleting therapies
Ultrasound-guided synovial biopsy:a systematic review according to the OMERACT filter and recommendations for minimal reporting standards in clinical studies
No full textOBJECTIVES: To describe existing techniques of US-guided synovial biopsy (USG-SB) and critically appraise the literature on this technology through the OMERACT filter.METHODS: USG-SB techniques are described and compared. A systematic literature search of PubMed and Embase was performed for original research reports including US and SB. The subjects, procedure protocols and reported results were analysed. A future research agenda is proposed.RESULTS: USG-SB can be performed using a portal-and-forceps or a dedicated semi-automatic guillotine-type biopsy needle approach. Of 50 reports identified, 7 were included in the review. Large, intermediate and small joints were all amenable to USG-SB. We found great heterogeneity with regard to indications for and definition of a successful procedure and of synovitis. Adverse events were assessed in most papers with an overall major complication rate of 0.4%. However, there was a lack of construct validity using a histological comparator. Relatively few papers reported details on the technique used, tissue processing, synovitis scoring and blinding for tissue analysis.CONCLUSION: USG-SB can be regarded as a valuable tool for large-scale synovial tissue sampling. Standardization of the techniques of USG-SB and tissue processing is needed. Future research should focus on the reliability, responsiveness and feasibility of this procedure in prospective studies.</p
The clinical and immunological significance of ectopic lymphoneogenesis in the rehumatoid synovial membrane
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
The clinical and immunological significance of ectopic lymphoneogenesis in the rehumatoid synovial membrane
No full textPhDDespite the development of new biomarkers predicting prognosis in rheumatoid
arthritis (RA) remains challenging and targeting of powerful biologics difficult.
The presence of ectopic germinal centres (GC) within synovium has long been
recognised (ectopic lymphoneogenesis [ELN]) and data have suggested that they
manufacture antibody (Ab). High affinity class switched Ab production occurs
through class switch recombination (CSR) and somatic hypermutation (SHM) both
critically dependent on activation induced cytidine deaminase (AID). However,
whether ectopic GCs express AID has not been known. Nonetheless data
associating ELN with disease severity suggest a role for ELN in RA pathogenesis
and as a potential biomarker. A classification system for RA synovium, based on
the concept of ELN has been proposed as: (i) aggregate, (ii) aggregate GC+ and,
(iii) an unorganised infiltrate. However whether these distinct pathotypes and/or
degree of aggregation equate to disease severity is unclear. Thus my first aim was
to develop and validate a pathological scoring system for rheumatoid synovium
capable of quantifying the degree of ELN. My second aim was to investigate
whether the presence and/or degree of ELN within the synovial membrane
correlated with both clinical phenotype and predicted erosive damage. I
demonstrate that the aggregational score developed is highly reliable and that ELN
within synovial tissue associates with a higher level of synovial inflammation but
is not predictive of damage.
My third aim was to investigate whether GCs within RA synovium were
functional. I provide evidence of functionality by demonstrating that ectopic GCs
invariably express AID, are surrounded by anti-CCP+ plasma cells, support
ongoing CSR and the manufacture of anti-CCP Abs.
My final aim was to characterise a cohort of synovial B cells consistently found
surrounding ectopic GCs. I identify a novel B cell subset within RA synovium,
interfollicular large B cells, (5)(5)(5) and demonstrate that interfollicular large B
cells in lymph node express a somatically mutated IgH.Guys and St Thomas' Charity fellowship
Synovial Tissue Sampling in Rheumatological Practice—Past Developments and Future Perspectives
No full textSynovial biopsies are performed in routine clinical care in order to refine diagnosis as well as within a research setting. Progress in the development of minimally invasive synovial sampling methods in the last century has accelerated and facilitated novel insights into disease pathogenesis. This review discusses the development of synovial biopsy techniques as well as examining the three currently most commonly used approaches: arthroscopic, blind needle biopsy and ultrasound guided approaches. It also highlights major research advances driven through synovial research and considers future developments
Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure
No full textThe aim of the present study was to perform an immunohistological assessment of the synovial tissue from involved small joints in rheumatoid arthritis (RA) and to explore the reliability of a mini-invasive ultrasound (US)-guided technique of small joint synovial biopsy for the histopathological assessment. Synovial tissue collected during arthrotomic surgery of small joints in nine patients served as the gold standard for the validation of the histological assessment. Small hand-joint synovial biopsies from an additional nine patients with erosive RA were obtained by a mini-invasive US-guided procedure, performed percutaneously by the portal and rigid forceps technique. Using digital image analysis, the area fractions of synovial macrophages (CD68 cells), T cells (CD3 cells) and B cells (CD20 cells) were measured in all high-power fields of every sample at different cutting levels. The representative sample was defined as the minimal number of high-power fields whose mean area fraction would reflect the overall mean area fraction within a percentage mean difference of 10%. For each patient, a range of three to five large samples for surgical biopsies and a range of 8-12 samples for US-guided biopsies were collected and analysed. In arthrotomic samples, the analysis of a randomly selected tissue area of 2.5 mm2 was representative of the overall value for CD68, CD3 and CD20 cells. US-guided samples allowed histological evaluation in 100% of cases, with a mean valid area of 18.56 mm2 (range 7.29-38.28 mm2). The analysis of a cumulative area of 2.5 mm2 from eight randomly selected sections (from different samples or from different cutting levels) allowed to reduce the percentage mean difference to less than 10% for CD68, CD3 and CD20 cells. In conclusion, US-guided synovial biopsy represents a reliable tool for the assessment of the histopathological features of RA patients with a mini-invasive approach
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