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Article ; Online: The Vitamin C Enantiomers Possess a Comparable Potency in the Induction of Oxidative Stress in Cancer Cells but Differ in Their Toxicity.

Begimbetova, Dinara / Burska, Agata N / Baltabekova, Aidana / Kussainova, Assiya / Kukanova, Assiya / Fazyl, Fatima / Ibragimova, Milana / Manekenova, Kenzhekyz / Makishev, Abay / Bersimbaev, Rakhmetkazhi I / Sarbassov, Dos D

International journal of molecular sciences

2024 Volume 25, Issue 5

Abstract: The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS) mutant cancer cells. VC with arsenic trioxide (ATO) is a promising drug combination ... ...

Abstract	The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS) mutant cancer cells. VC with arsenic trioxide (ATO) is a promising drug combination that might lead to the development of effective cancer therapeutics. Considering that a tumor suppressive effect of VC requires its high-dose administration, it is of interest to examine the toxicity of two enantiomers of VC (enantiomer d-optical isomer D-VC and natural l-optical isomer L-VC) in vitro and in vivo. We show that the combinations of L-VC with ATO and D-VC with ATO induced a similar cytotoxic oxidative stress in Kras
MeSH term(s)	Animals ; Mice ; Ascorbic Acid/pharmacology ; Proto-Oncogene Proteins p21(ras) ; Oxidative Stress ; Vitamins/pharmacology ; Arsenic Trioxide/pharmacology ; Neoplasms
Chemical Substances	Ascorbic Acid (PQ6CK8PD0R) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Vitamins ; Arsenic Trioxide (S7V92P67HO)
Language	English
Publishing date	2024-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25052531
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Article ; Online: Interferon-related gene expression in response to TNF inhibitor treatment in ankylosing spondylitis patients: a pilot study.

Harrison, Stephanie R / Burska, Agata N / Emery, Paul / Marzo-Ortega, Helena / Ponchel, Frederique

Rheumatology (Oxford, England)

2021 Volume 60, Issue 8, Page(s) 3607–3616

Abstract: Objective: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the spine and sacroiliac joints. TNF inhibitor (TNFi) drugs are recommended for patients not responding to NSAIDs; however, there is a significant need for ... ...

Abstract	Objective: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the spine and sacroiliac joints. TNF inhibitor (TNFi) drugs are recommended for patients not responding to NSAIDs; however, there is a significant need for biomarkers of response. IFN-regulated genes (IRGs) and other cytokines/chemokines are linked to autoimmune diseases and have been associated with treatment response. Our objective was to explore whether IRGs and cytokines/chemokines can be associated with response to TNFiagents in AS. Methods: Peripheral blood mononuclear cells were obtained from 26 AS patients who were to receive a TNFi (I, n = 15) or placebo (P, n = 11) at week 0 and week 22. Response (R)/non-response (NR) was defined as reduction in ASDAS ≥ 1.2 points or reduction in sacroiliac/vertebral MRI lesions. The expression of 96 genes was quantified using TaqMan assays. Finally, ELISA was used to measure IL-6 in serum samples from another 38 AS patients. Results: Analysis of gene expression in 26 baseline samples segregated patients into four groups defined by a signature of 15 genes (mainly IRGs). ASDAS response was associated with one group independently of treatment received. We then analysed response to the TNFi (n = 15) and identified a 12-gene signature associated with MRI response. A third IRG signature was also associated with a reduction in IRGs expression post-TNFi samples (n = 10 pairs). Finally, decreased circulating IL-6 was associated with BASDAI-R. Conclusion: This pilot study suggests an association between IRG expression and response to TNFi in AS. These findings require validation in a larger cohort in order to construct predictive algorithms for patient stratification.
MeSH term(s)	Adult ; Aged ; Biomarkers/blood ; Female ; Gene Expression Regulation/drug effects ; Humans ; Interferon Type I/metabolism ; Interleukin-6/blood ; Male ; Middle Aged ; Pilot Projects ; Spondylitis, Ankylosing/blood ; Spondylitis, Ankylosing/drug therapy ; Tumor Necrosis Factor Inhibitors/pharmacology ; Tumor Necrosis Factor Inhibitors/therapeutic use ; Young Adult
Chemical Substances	Biomarkers ; Interferon Type I ; Interleukin-6 ; Tumor Necrosis Factor Inhibitors
Language	English
Publishing date	2021-01-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keaa817
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Article ; Online: Enhancing an Oxidative "Trojan Horse" Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside.

Burska, Agata N / Ilyassova, Bayansulu / Dildabek, Aruzhan / Khamijan, Medina / Begimbetova, Dinara / Molnár, Ferdinand / Sarbassov, Dos D

Cells

2022 Volume 11, Issue 21

Abstract: The turn-on mutations of ... ...

Abstract	The turn-on mutations of the
MeSH term(s)	Humans ; Arsenic Trioxide/pharmacology ; Arsenic Trioxide/therapeutic use ; Ascorbic Acid/pharmacology ; Ascorbic Acid/therapeutic use ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Reactive Oxygen Species/metabolism ; Cell Line, Tumor ; Oxidative Stress ; Vitamins/pharmacology ; Oxidation-Reduction ; Neoplasms/drug therapy ; Neoplasms/genetics
Chemical Substances	Arsenic Trioxide (S7V92P67HO) ; Ascorbic Acid (PQ6CK8PD0R) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Reactive Oxygen Species ; Vitamins ; KRAS protein, human
Language	English
Publishing date	2022-11-01
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11213454
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Article: Synovial Tissue Heterogeneity in Rheumatoid Arthritis and Changes With Biologic and Targeted Synthetic Therapies to Inform Stratified Therapy.

Ouboussad, Lylia / Burska, Agata N / Melville, Andrew / Buch, Maya H

Frontiers in medicine

2019 Volume 6, Page(s) 45

Abstract: The treatment of rheumatoid arthritis (RA) has been transformed with the introduction of biologic disease modifying anti-rheumatic drugs (bDMARD) and more recently, targeted synthetic DMARD (tsDMARD) therapies in the form of janus-kinase inhibitors. ... ...

Abstract	The treatment of rheumatoid arthritis (RA) has been transformed with the introduction of biologic disease modifying anti-rheumatic drugs (bDMARD) and more recently, targeted synthetic DMARD (tsDMARD) therapies in the form of janus-kinase inhibitors. Nevertheless, response to these agents varies such that a trial and error approach is adopted; leading to poor patient quality of life, and long-term outcomes. There is thus an urgent need to identify effective biomarkers to guide treatment selection. A wealth of research has been invested in this field but with minimal progress. Increasingly recognized is the importance of evaluating synovial tissue, the primary site of RA, as opposed to peripheral blood-based investigation. In this mini-review, we summarize the literature supporting synovial tissue heterogeneity, the conceptual basis for stratified therapy. This includes recognition of distinct synovial pathobiological subtypes and associated molecular pathways. We also review synovial tissue studies that have been conducted to evaluate the effect of individual bDMARD and tsDMARD on the cellular and molecular characteristics, with a view to identifying tissue predictors of response. Initial observations are being brought into the clinical trial landscape with stratified biopsy trials to validate toward implementation. Furthermore, development of tissue based omics technology holds still more promise in advancing our understanding of disease processes and guiding future drug selection.
Language	English
Publishing date	2019-03-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2019.00045
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Article: Dynamics of Early Signalling Events during Fracture Healing and Potential Serum Biomarkers of Fracture Non-Union in Humans.

Burska, Agata N / Giannoudis, Peter V / Tan, Boon Hiang / Ilas, Dragos / Jones, Elena / Ponchel, Frederique

Journal of clinical medicine

2020 Volume 9, Issue 2

Abstract: To characterise the dynamic of events during the early phases of fracture repair in humans, we investigated molecular events using gene expression profiling of bone fragments from the fracture site at different time points after trauma and immune/stromal ...

Abstract	To characterise the dynamic of events during the early phases of fracture repair in humans, we investigated molecular events using gene expression profiling of bone fragments from the fracture site at different time points after trauma and immune/stromal cells recruitment at the fracture site using flow cytometry. Bone and inflammatory markers were expressed at low levels at homeostasis, while transcripts for bone constituent proteins were consistently detected at higher levels. Early after fracture (range 2-4 days), increased expression of CXCL12, suggested recruitment of immune cells associated with a change in the balance of degradation enzymes and their inhibitors. At intermediate time after fracture (4-8 days), we observed high expression of inflammatory cytokines (IL1-beta, IL6), CCL2, the T-cell activation marker CD69. Late after fracture (8-14 days), high expression of factors co-operating towards the regulation of bone turnover was detected. We identified potential soluble factors and explored circulating levels in patients for whom a union/non-union (U/NU) outcome was known. This showed a clear difference for PlGF (
Language	English
Publishing date	2020-02-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm9020492
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Article ; Online: Gene Expression and Autoantibody Analysis Revealing Distinct Ancestry-Specific Profiles Associated With Response to Rituximab in Refractory Systemic Lupus Erythematosus.

Carter, Lucy M / Alase, Adewonuola / Wigston, Zoe / Psarras, Antonios / Burska, Agata / Sutton, Emily / Yusof, Md Yuzaiful Md / Reynolds, John A / McHugh, Neil / Emery, Paul / Wittmann, Miriam / Bruce, Ian N / Vital, Edward M

Arthritis & rheumatology (Hoboken, N.J.)

2023 Volume 75, Issue 5, Page(s) 697–710

Abstract: Objective: Gene expression profiles are associated with the clinical heterogeneity of systemic lupus erythematosus (SLE) but are not well studied as biomarkers for therapy. We studied gene expression and response to rituximab in a multiethnic UK cohort ... ...

Abstract	Objective: Gene expression profiles are associated with the clinical heterogeneity of systemic lupus erythematosus (SLE) but are not well studied as biomarkers for therapy. We studied gene expression and response to rituximab in a multiethnic UK cohort who were refractory to standard therapy. Methods: We evaluated baseline expression levels of transcripts known to associate with clinical features of SLE using a 96-probe TaqMan array and whole blood samples from 213 patients with active SLE who had been prospectively enrolled in the British Isles Lupus Assessment Group (BILAG) Biologics Register. We measured autoantibodies using immunoprecipitation and enzyme-linked immunosorbent assays. We determined responses to first-cycle rituximab at 6 months from treatment start in 110 SLE patients by assessing BILAG 2004 disease activity. Results: Interferon gene expression scores were lower in patients of European ancestry than in all other ancestry groups. The relationship between blood interferon gene expression scores and scores annotated to plasmablasts, neutrophils, myeloid lineage, inflammation, and erythropoiesis differed between patients of European and non-European ancestries. Hierarchical clustering revealed 3 distinct non-European ancestry patient subsets with stratified responses to rituximab that were not explained by sociodemographic and clinical variables, with responses lowest in an interferon-low, neutrophil-high cluster and highest in a cluster with high expression levels across all signatures (P < 0.001). Clusters in European ancestry patients did not predict response to rituximab but segregated patients by global disease activity and renal involvement. In both ancestral groups, interferon-high clusters were associated with U1 RNP/Sm antibodies. Conclusion: Ancestry appears central to the immunologic and clinical heterogeneity in SLE. These results suggest that ancestry, disease activity, and transcriptional signatures could each assist in predicting the effectiveness of B cell depletion therapies.
MeSH term(s)	Humans ; Rituximab/therapeutic use ; Autoantibodies ; B-Lymphocytes ; Treatment Outcome ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/genetics ; Antibodies, Antinuclear ; Interferons ; Gene Expression
Chemical Substances	Rituximab (4F4X42SYQ6) ; Autoantibodies ; Antibodies, Antinuclear ; Interferons (9008-11-1)
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.42404
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Article ; Online: Comparison of the free and total light chain assays in serum and urine samples with immunofixation electrophoresis for detecting monoclonal proteins in patients with monoclonal gammopathy

Korpysz Maciej / Morawska Marta / Burska Agata / Donica Helena

Current Issues in Pharmacy and Medical Sciences, Vol 27, Iss 3, Pp 165-

2014 Volume 170

Abstract: Monoclonal protein (M-protein) is produced by a malignant clone of plasma cells. Detected in serum and/or urine, this typically indicates multiple myeloma (MM) or other monoclonal gammopathy (MG). In a majority of MM cases, with the production of intact ... ...

Abstract	Monoclonal protein (M-protein) is produced by a malignant clone of plasma cells. Detected in serum and/or urine, this typically indicates multiple myeloma (MM) or other monoclonal gammopathy (MG). In a majority of MM cases, with the production of intact monoclonal immunoglobulin (Ig), malignant plasmocytes and/or B lymphocytes often produce excessive amounts of free light chains (FLCs). Excessive synthesis of FLCs lowers the ability of renal proximal tubules to re-absorb FLCs, which results in abnormally high levels of FLCs in the urine (Bence Jones protein, BJP). In laboratory practice, there are tests available for the quantitative measurement of only FLCs κ and λ or for total light chains (TLCs). These tests measure both free forms and bound in the (Ig) molecules forms as light chains that are evident in the serum and in urine. The purpose of this study was to evaluate the FLCs and TLCs approaches in screening serum and urine samples of patients with MM, doing so in comparison to the results of immunofixation (IFE) assessment. A second purpose was to assess the suitability of the collected material for obtaining the most reliable results. The results of serum FLCs (sFLCs) assays suggest that this approach is of the highest reliability and diagnostic usefulness in the detection of MG with excess production of FLCs, in comparison to other available tests. In our work, when κ band light chains were detected in serum IFE (sIFE), 91% patients had their FLCs concentrations beyond the reference range, whereas 89% patients had increased λ FLCs when λ band light chains were detected in sIFE. We also found abnormal sFLC κ/λ ratios in 86.4% and 88.9% of all subject patients who had κ or λ band light chains detected in their sIFE, respectively.
Keywords	free light chains ; total light chains ; monoclonal gammopathy ; multiple myeloma ; immunofixation ; Medicine ; R
Subject code	610
Language	English
Publishing date	2014-09-01T00:00:00Z
Publisher	Sciendo
Document type	Article ; Online
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Article ; Online: Type I interferon pathway assays in studies of rheumatic and musculoskeletal diseases: a systematic literature review informing EULAR points to consider.

Burska, Agata / Rodríguez-Carrio, Javier / Biesen, Robert / Dik, Willem A / Eloranta, Maija-Leena / Cavalli, Giulio / Visser, Marianne / Boumpas, Dimitrios T / Bertsias, George / Wahren-Herlenius, Marie / Rehwinkel, Jan / Frémond, Marie-Louise / Crow, Mary K / Ronnblom, Lars / Conaghan, P G / Versnel, Marjan / Vital, Ed

RMD open

2023 Volume 9, Issue 1

Abstract: Objectives: To systematically review the literature for assay methods that aim to evaluate type I interferon (IFN-I) pathway activation and to harmonise-related terminology.: Methods: Three databases were searched for reports of IFN-I and rheumatic ... ...

Abstract	Objectives: To systematically review the literature for assay methods that aim to evaluate type I interferon (IFN-I) pathway activation and to harmonise-related terminology. Methods: Three databases were searched for reports of IFN-I and rheumatic musculoskeletal diseases. Information about the performance metrics of assays measuring IFN-I and measures of truth were extracted and summarised. A EULAR task force panel assessed feasibility and developed consensus terminology. Results: Of 10 037 abstracts, 276 fulfilled eligibility criteria for data extraction. Some reported more than one technique to measure IFN-I pathway activation. Hence, 276 papers generated data on 412 methods. IFN-I pathway activation was measured using: qPCR (n=121), immunoassays (n=101), microarray (n=69), reporter cell assay (n=38), DNA methylation (n=14), flow cytometry (n=14), cytopathic effect assay (n=11), RNA sequencing (n=9), plaque reduction assay (n=8), Nanostring (n=5), bisulphite sequencing (n=3). Principles of each assay are summarised for content validity. Concurrent validity (correlation with other IFN assays) was presented for n=150/412 assays. Reliability data were variable and provided for 13 assays. Gene expression and immunoassays were considered most feasible. Consensus terminology to define different aspects of IFN-I research and practice was produced. Conclusions: Diverse methods have been reported as IFN-I assays and these differ in what elements or aspects of IFN-I pathway activation they measure and how. No 'gold standard' represents the entirety of the IFN pathway, some may not be specific for IFN-I. Data on reliability or comparing assays were limited, and feasibility is a challenge for many assays. Consensus terminology should improve consistency of reporting.
MeSH term(s)	Humans ; Interferon Type I ; Reproducibility of Results ; Musculoskeletal Diseases/diagnosis ; Musculoskeletal Diseases/etiology ; Rheumatic Diseases/diagnosis ; Advisory Committees
Chemical Substances	Interferon Type I
Language	English
Publishing date	2023-02-28
Publishing country	England
Document type	Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2022-002876
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Article ; Online: Association between type I interferon pathway activation and clinical outcomes in rheumatic and musculoskeletal diseases: a systematic literature review informing EULAR points to consider.

Rodríguez-Carrio, Javier / Burska, Agata / Conaghan, P G / Dik, Willem A / Biesen, Robert / Eloranta, Maija-Leena / Cavalli, Giulio / Visser, Marianne / Boumpas, Dimitrios T / Bertsias, George / Wahren-Herlenius, Marie / Rehwinkel, Jan / Frémond, Marie-Louise / Crow, Mary K / Ronnblom, Lars / Vital, Ed / Versnel, Marjan

RMD open

2023 Volume 9, Issue 1

Abstract: Background: Type I interferons (IFN-I) contribute to a broad range of rheumatic and musculoskeletal diseases (RMDs). Compelling evidence suggests that the measurement of IFN-I pathway activation may have clinical value. Although several IFN-I pathway ... ...

Abstract	Background: Type I interferons (IFN-I) contribute to a broad range of rheumatic and musculoskeletal diseases (RMDs). Compelling evidence suggests that the measurement of IFN-I pathway activation may have clinical value. Although several IFN-I pathway assays have been proposed, the exact clinical applications are unclear. We summarise the evidence on the potential clinical utility of assays measuring IFN-I pathway activation. Methods: A systematic literature review was conducted across three databases to evaluate the use of IFN-I assays in diagnosis and monitor disease activity, prognosis, response to treatment and responsiveness to change in several RMDs. Results: Of 366 screened, 276 studies were selected that reported the use of assays reflecting IFN-I pathway activation for disease diagnosis (n=188), assessment of disease activity (n=122), prognosis (n=20), response to treatment (n=23) and assay responsiveness (n=59). Immunoassays, quantitative PCR (qPCR) and microarrays were reported most frequently, while systemic lupus erythematosus (SLE), rheumatoid arthritis, myositis, systemic sclerosis and primary Sjögren's syndrome were the most studied RMDs. The literature demonstrated significant heterogeneity in techniques, analytical conditions, risk of bias and application in diseases. Inadequate study designs and technical heterogeneity were the main limitations. IFN-I pathway activation was associated with disease activity and flare occurrence in SLE, but their incremental value was uncertain. IFN-I pathway activation may predict response to IFN-I targeting therapies and may predict response to different treatments. Conclusions: Evidence indicates potential clinical value of assays measuring IFN-I pathway activation in several RMDs, but assay harmonisation and clinical validation are urged. This review informs the EULAR points to consider for the measurement and reporting of IFN-I pathway assays.
MeSH term(s)	Humans ; Interferon Type I ; Musculoskeletal Diseases/diagnosis ; Musculoskeletal Diseases/etiology ; Myositis ; Lupus Erythematosus, Systemic/diagnosis
Chemical Substances	Interferon Type I
Language	English
Publishing date	2023-03-08
Publishing country	England
Document type	Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2022-002864
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Article ; Online: 2022 EULAR points to consider for the measurement, reporting and application of IFN-I pathway activation assays in clinical research and practice.

Rodríguez-Carrio, Javier / Burska, Agata / Conaghan, Philip G / Dik, Willem A / Biesen, Robert / Eloranta, Maija-Leena / Cavalli, Giulio / Visser, Marianne / Boumpas, Dimitrios T / Bertsias, George / Wahren-Herlenius, Marie / Rehwinkel, Jan / Frémond, Marie-Louise / Crow, Mary K / Rönnblom, Lars / Versnel, Marjan A / Vital, Edward M

Annals of the rheumatic diseases

2023 Volume 82, Issue 6, Page(s) 754–762

Abstract: Background: Type I interferons (IFN-Is) play a role in a broad range of rheumatic and musculoskeletal diseases (RMDs), and compelling evidence suggests that their measurement could have clinical value, although testing has not progressed into clinical ... ...

Abstract	Background: Type I interferons (IFN-Is) play a role in a broad range of rheumatic and musculoskeletal diseases (RMDs), and compelling evidence suggests that their measurement could have clinical value, although testing has not progressed into clinical settings. Objective: To develop evidence-based points to consider (PtC) for the measurement and reporting of IFN-I assays in clinical research and to determine their potential clinical utility. Methods: EULAR standardised operating procedures were followed. A task force including rheumatologists, immunologists, translational scientists and a patient partner was formed. Two systematic reviews were conducted to address methodological and clinical questions. PtC were formulated based on the retrieved evidence and expert opinion. Level of evidence and agreement was determined. Results: Two overarching principles and 11 PtC were defined. The first set (PtC 1-4) concerned terminology, assay characteristics and reporting practices to enable more consistent reporting and facilitate translation and collaborations. The second set (PtC 5-11) addressed clinical applications for diagnosis and outcome assessments, including disease activity, prognosis and prediction of treatment response. The mean level of agreement was generally high, mainly in the first PtC set and for clinical applications in systemic lupus erythematosus. Harmonisation of assay methodology and clinical validation were key points for the research agenda. Conclusions: IFN-I assays have a high potential for implementation in the clinical management of RMDs. Uptake of these PtC will facilitate the progress of IFN-I assays into clinical practice and may be also of interest beyond rheumatology.
MeSH term(s)	Humans ; Musculoskeletal Diseases ; Rheumatology
Language	English
Publishing date	2023-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/ard-2022-223628
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