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1.
Artigo em Inglês | MEDLINE | ID: mdl-33521807

RESUMO

OBJECTIVES: To investigate whether Fluorescence Optical Imaging (FOI) enhancement and Magnetic Resonance Imaging (MRI)-defined synovitis are associated with pain and physical function in hand osteoarthritis (OA) patients. METHODS: Bilateral FOI scans and MRI of the dominant hand were available for 221 patients. Finger joints were examined for tenderness on palpation. Pain in individual finger joints during the last 24 h and last 6 weeks and hand pain intensity by the Australian/Canadian hand index and Numeric Rating Scale were self-reported. On joint level, we applied logistic regression with generalized estimating equations to examine whether FOI enhancement and MRI-defined synovitis were associated with pain in the same joint. On subject level, we applied linear regression to assess whether FOI and MRI sum scores were associated with pain intensity and physical function. RESULTS: Metacarpophalangeal and thumb base joints were excluded from analyses due to little/no FOI enhancement. Finger joints with FOI enhancement on the composite image had higher odds (95% confidence interval) of pain during the last 6 weeks (grade 1: 1.4 (1.2-1.6), grade 2-3: 2.1 (1.7-2.6)). Similar results were found for joint pain during the last 24 h and joint tenderness in fingers. Numerically stronger associations were found between MRI-defined synovitis and finger joint pain/tenderness. FOI and MRI sum scores demonstrated no/weak associations with hand pain and physical function. CONCLUSION: FOI enhancement and MRI-defined synovitis were associated with pain in the same finger joint. None of the imaging modalities demonstrated consistent associations with pain, stiffness and physical function on subject level.

2.
Int J Mol Sci ; 21(23)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33256266

RESUMO

The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging evidence suggests JAK/STAT signaling pathway plays an important role in bone development, metabolism, and healing. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. Here, we summarize the role of JAK/STAT pathway on development, homeostasis, and regeneration based on skeletal phenotype of individual JAK and STAT gene knockout models and selective inhibition of components of the JAK/STAT signaling including influences of JAK inhibition in osteoclasts, osteoblasts, and osteocytes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33085747

RESUMO

BACKGROUND: To assess the reliability of the consensually agreed US definitions of major salivary gland lesions and the US scoring system for salivary gland assessment in patients with SS. METHODS: Nine experienced sonographers scanned and read the US images of both parotid glands (PGs) and submandibular glands (SMGs) in eight patients with primary and secondary SS in two rounds. A consensually agreed four-grade semi-quantitative scoring was applied in B-mode for morphological lesions: grade 0, normal; grade 1, mild inhomogeneity without anechoic or hypoechoic areas; grade 2, moderate inhomogeneity with focal anechoic or hypoechoic areas; grade 3, severe inhomogeneity with diffuse an- or hypoechoic areas occupying the entire gland or fibrous gland. The presence or absence of typical SS lesions, i.e. the Sjögren's signature, was scored binary. Intra- and interreader reliabilities were computed using weighted and unweighted Cohen's and Light's κ coefficients. RESULTS: The mean prevalence of grades 0-3 in PG were 43, 17, 23 and 31% and 28, 14, 33 and 32% for the SMGs, respectively. The weighted κ for intrareader reliability ranged from 0.44 to 1 for grading and 0.64 to 1 for the Sjögren's signature of PG and 0.59 to 1 and -0.09 to 0.6 for SMGs, respectively. The interreader reliability κ for grading in PG was 0.62 (95% CI 0.47, 0.74) and for Sjögren's signature it was 0.36 (95% CI 0, 0.43); in SMG it was 0.62 (95% CI 0.47, 0.72) and 0.03 (95% CI 0, 0.07) respectively. CONCLUSIONS: The consensually agreed novel US scoring system for major salivary gland lesions showed substantial intra- and interreader reliability in patients with SS. The reliability of the Sjögren's signature was moderate.

4.
Arthritis Res Ther ; 22(1): 98, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357904

RESUMO

OBJECTIVE: Fluorescence optical imaging (FOI) demonstrates enhanced microcirculation in finger joints as a sign of inflammation. We wanted to assess the validity and diagnostic performance of FOI measuring synovitis in persons with hand OA, comparing it with magnetic resonance imaging (MRI)- and ultrasound-detected synovitis. METHODS: Two hundred and twenty-one participants with hand OA underwent FOI and ultrasound (gray-scale synovitis and power Doppler activity) of the bilateral hands and contrast-enhanced MRI examination of the dominant hand. Fifteen joints in each hand were scored on semi-quantitative scales (grade 0-3) for all modalities. Four FOI images were evaluated: one composite image (Prima Vista Mode (PVM)) and three images representing phases of fluorescent dye distribution. Spearman's correlation coefficients were calculated between sum scores of FOI, MRI, and ultrasound. Sensitivity, specificity, and area under the curve (AUC) were calculated for FOI using MRI or ultrasound as reference. RESULTS: FOI did not demonstrate enhancement in the thumb base, and the joint was excluded from further analyses. FOI sum scores showed poor to fair correlations with MRI (rho 0.01-0.24) and GS synovitis sum scores (rho 0.12-0.25). None of the FOI images demonstrated both good sensitivity and specificity, and the AUC ranged from 0.50-0.61 and 0.51-0.63 with MRI and GS synovitis as reference, respectively. FOI demonstrated similar diagnostic performance with PD activity and GS synovitis as reference. CONCLUSION: FOI enhancement correlated poorly with synovitis assessed by more established imaging modalities, questioning the value of FOI for the evaluation of synovitis in hand OA.

5.
Sci Rep ; 10(1): 7907, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404914

RESUMO

Advances in microbiome research suggest involvement in chronic inflammatory diseases such as rheumatoid arthritis (RA). Searching for initial trigger(s) in RA, we compared transcriptome profiles of highly inflamed RA synovial tissue (RA-ST) and osteoarthritis (OA)-ST with 182 selected reference transcriptomes of defined cell types and their activation by exogenous (microbial) and endogenous inflammatory stimuli. Screening for dominant changes in RA-ST demonstrated activation of monocytes/macrophages with gene-patterns induced by bacterial and fungal triggers. Gene-patterns of activated B- or T-cells in RA-ST reflected a response to activated monocytes/macrophages rather than inducing their activation. In contrast, OA-ST was dominated by gene-patterns of non-activated macrophages and fibroblasts. The difference between RA and OA was more prominent in transcripts of secreted proteins and was confirmed by protein quantification in synovial fluid (SF) and serum. In total, 24 proteins of activated cells were confirmed in RA-SF compared to OA-SF and some like CXCL13, CCL18, S100A8/A9, sCD14, LBP reflected this increase even in RA serum. Consequently, pathogen-like response patterns in RA suggest that direct microbial influences exist. This challenges the current concept of autoimmunity and immunosuppressive treatment and advocates new diagnostic and therapeutic strategies that consider microbial persistence as important trigger(s) in the etiopathogenesis of RA.

7.
Int J Mol Sci ; 21(3)2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32013232

RESUMO

Both inflammatory diseases like rheumatoid arthritis (RA) and anti-inflammatory treatment of RA with glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs) negatively influence bone metabolism and fracture healing. Janus kinase (JAK) inhibition with tofacitinib has been demonstrated to act as a potent anti-inflammatory therapeutic agent in the treatment of RA, but its impact on the fundamental processes of bone regeneration is currently controversially discussed and at least in part elusive. Therefore, in this study, we aimed to examine the effects of tofacitinib on processes of bone healing focusing on recruitment of human mesenchymal stromal cells (hMSCs) into the inflammatory microenvironment of the fracture gap, chondrogenesis, osteogenesis and osteoclastogenesis. We performed our analyses under conditions of reduced oxygen availability in order to mimic the in vivo situation of the fracture gap most optimal. We demonstrate that tofacitinib dose-dependently promotes the recruitment of hMSCs under hypoxia but inhibits recruitment of hMSCs under normoxia. With regard to the chondrogenic differentiation of hMSCs, we demonstrate that tofacitinib does not inhibit survival at therapeutically relevant doses of 10-100 nM. Moreover, tofacitinib dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity. We conclude from our data that tofacitinib may influence bone healing by promotion of hMSC recruitment into the hypoxic microenvironment of the fracture gap but does not interfere with the cartilaginous phase of the soft callus phase of fracture healing process. We assume that tofacitinib may promote bone formation and reduce bone resorption, which could in part explain the positive impact of tofacitinib on bone erosions in RA. Thus, we hypothesize that it will be unnecessary to stop this medication in case of fracture and suggest that positive effects on osteoporosis are likely.


Assuntos
Inibidores de Janus Quinases/farmacologia , Janus Quinases/metabolismo , Osteogênese/efeitos dos fármacos , Piperidinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Hipóxia Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrogênese/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Janus Quinases/antagonistas & inibidores , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-33386164

RESUMO

AIMS: To analyze whether there is sufficient data from published literature to demonstrate that ultrasound, including elastography, present good metric properties (truth, discrimination and feasibility) in autoimmune myositis (AIM). METHODS: A population, intervention, comparator and outcome-structured (PICO) search was performed in Medline, Cochrane Library and Embase database from 01/01/1973 to 08/05/2019. The inclusion criteria required original research involving adult humans, reported in English, assessing ultrasound and elastography in patients with an AIM. Conference abstracts and computer-assisted diagnostics that focused on technique and not ultrasound domains were excluded. RESULTS: Approximately 2670 articles were identified. Forty-one full-text articles were included in the final analysis. There were 551 AIM patients studied. Eighteen studies (43.9%) had a control group, of which 15 (63.3%) were healthy controls. The age of participants (including controls) varied from 18 to 86 years, and most were females (59%). Diagnosis of AIM was largely biopsy-proven, although some were derived through clinical presentation, positive clinical imaging (ultrasound or otherwise) and/or electromyography and steroid responsiveness. The features examined with ultrasound in the 41 included articles consisted of: muscle echogenicity, bulk, atrophy, architecture, power Doppler, perfusion characteristics, shear wave modulus, shear wave velocity, elasticity index and fasciculations. Twelve studies (29.2%) used quantitative methods to assess these characteristics, whilst others used semi-quantitative, dichotomous/binary and descriptive scoring systems. Criterion validity was met in 14 studies (12/14, 85.7%) and construct validity in 22 studies (22/25, 88.0%). Most published articles reported Level 3b to Level 5 evidence with varying degrees of bias. There was only one longitudinal study examining discrimination. Reliability and feasibility were under-reported. CONCLUSION: This is the first systematic review studying the utility of ultrasound, including elastography, in AIM. There is some evidence for criterion and construct validity, suggesting that ultrasound may be a promising outcome measurement instrument in AIM. Agreement on the standardization of acquisition, and the definitions of target domains, is required. Additionally, further validation studies are required to determine discrimination, reliability and feasibility.

10.
Arthritis Res Ther ; 21(1): 209, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533820

RESUMO

BACKGROUND: Fluorescence optical imaging (FOI) enables visualization of inflammation in the hands in rheumatic joint diseases with currently a lack of long-term follow-up studies. OBJECTIVE: To investigate FOI for treatment monitoring in a homogenous cohort of patients with early (disease duration < 2 years) and active (DAS28 > 3.2) RA over a period of 12 months. METHODS: Thirty-five RA patients (24 (68.6%) females, mean age 53.3 years (SD 13.6)) were investigated clinically by DAS28, tender joint count (TJC) and swollen joint count (SJC) and by FOI in phases 1-3 and PrimaVistaMode (PVM) before therapy change and after 12 months. The FOI activity score (FOIAS) was calculated based on individual joint scores from 0 to 3 in 30 joints per patient, adding up to a sum score (0-90). RESULTS: We found a statistically significant reduction of FOIAS in phase 1 from baseline (median 5.0, IQR 24.96) to follow-up (median 1.0, IQR 4.0) in all patients (p = 0.0045), both in responders and non-responders according to EULAR response criteria by DAS28. Statistically significant reductions over 12 months were found for median DAS28(ESR) 5.61 to 3.31, TJC 7.0 to 1.0, and SJC 5.0 to 1.0 (each p <  0.001). No statistically significant correlations were detected between the FOIAS change in phase 1 and DAS28(ESR), TJC, or SJC. Correlations between the other phases and clinical outcomes were weak to moderate. CONCLUSION: Reduced early enhancement in FOI phase 1 can be observed in clinically responding and non-responding early RA patients under treatment. Regarding potential marker performance, FOI probably shows a reduction of inflammation more objectively.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Imagem Óptica/métodos , Idoso , Artrite Reumatoide/tratamento farmacológico , Feminino , Fluorescência , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo
11.
J Dtsch Dermatol Ges ; 17(9): 913-921, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31538737

RESUMO

OBJECTIVE: Comparison of fluorescence optical imaging (FOI) with grayscale (GS) and power Doppler ultrasound (PDUS) to detect joint inflammation in patients with confirmed or suspected psoriatic arthritis (PsA). METHODS: Patients (n = 60) with psoriasis and tenderness and/or swelling of joints were separated into two groups: diagnosis confirmed by the treating dermatologist before the start of the study (n = 26), and suspected PsA (n = 34). GS/PDUS of the hand most clinically affected was performed with a dorsal/palmar view (wrist, MCP, PIP, DIP2-5). FOI examination was carried out in a standardized manner by analyzing the predefined Phases 1-3. RESULTS: FOI was found to be more sensitive than ultrasound (US) for detection of inflammation in PIP/DIP joints (p = 0.035). Confirmed PsA patients showed more findings in FOI P2 and P3, while suspected PsA patients showed more findings in P1. In the confirmed PsA group, most involved joints were MCP joints, while in the suspected PsA group, more involved wrist joints and DIP joints (p = 0.006) were detected with FOI. CONCLUSIONS: The differences between the confirmed and suspected groups indicate that FOI is helpful in the detection of early PsA since P1 may correspond to acute inflammation, whereas P2 and P3 enhancement reflect chronic inflammation. Fluorescence optical imaging might therefore be a novel diagnostic tool for early PsA diagnosis.


Assuntos
Artrite Psoriásica/diagnóstico por imagem , Adulto , Idoso , Diagnóstico Precoce , Edema/diagnóstico por imagem , Feminino , Articulações dos Dedos/diagnóstico por imagem , Dermatoses da Mão/diagnóstico por imagem , Humanos , Masculino , Microscopia de Fluorescência/métodos , Pessoa de Meia-Idade , Dor Musculoesquelética/diagnóstico por imagem , Imagem Óptica/métodos , Ultrassonografia , Articulação do Punho/diagnóstico por imagem
13.
J Rheumatol ; 46(10): 1379-1387, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31203213

RESUMO

OBJECTIVE: To identify and synthesize the best available evidence on the application of musculoskeletal (MSK) ultrasound (US) in patients with systemic lupus erythematosus (SLE) and to present the measurement properties of US in different elementary lesions and pathologies. METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library was performed. Original articles were included that were published in English between August 1, 2014, and December 31, 2018, reporting US, Doppler, synovitis, joint effusion, bone erosion, tenosynovitis, and enthesitis in patients with SLE. Data extraction focused on the definition and quantification of US-detected synovitis, joint effusion, bone erosion, tenosynovitis, enthesitis, and the measurement properties of US according to the OMERACT Filter 2.1 instruments selection. RESULTS: Of the 143 identified articles, 15 were included. Most articles were cross-sectional studies (14/15, 93%). The majority of the studies used the OMERACT definitions for ultrasonographic pathology. Regarding the measurement properties of US in different elementary lesions and pathologies, all studies dealt with face validity, content validity, and feasibility. Most studies achieved construct validity. Concerning the reliability of image reading, 1 study (1/15, 7%) assessed both intraobserver and interobserver reliability. For image acquisition, 4 studies (4/15, 27%) evaluated interobserver reliability and none had evaluated intraobserver reliability. Criterion validity was assessed in 1 study (1/15, 7%). Responsiveness was not considered in any of the studies. CONCLUSION: This literature review demonstrates the need for further research and validation work to define the involvement of US as an outcome measurement instrument for the MSK manifestations in patients with SLE.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Sistema Musculoesquelético/diagnóstico por imagem , Avaliação de Resultados em Cuidados de Saúde/métodos , Ultrassonografia Doppler/métodos , Adulto , Artrite Psoriásica/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagem , Estudos Transversais , Entesopatia/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Sinovite/diagnóstico por imagem , Tenossinovite/diagnóstico por imagem
14.
Ann Rheum Dis ; 78(7): 967-973, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31036626

RESUMO

OBJECTIVE: To develop ultrasound (US) definitions and a US novel scoring system for major salivary gland (SG) lesions in patients with primary Sjögren's syndrome (pSS) and to test their intrareader and inter-reader reliability using US video clips. METHODS: Twenty-five rheumatologists were subjected to a three-round, web-based Delphi process in order to agree on (1) definitions and scanning procedure of salivary gland ultrasonography (SGUS): parotid, submandibular and sublingual glands (PG, SMG and SLG); (2) definitions for the elementary SGUS lesions in patients with Sjögren's syndrome; (3) scoring system for grading changes. The experts rated the statements on a 1-5 Likert scale. In the second step, SGUS video clips of patients with pSS and non-pSS sicca cases were collected containing various spectrums of disease severity followed by an intrareader and inter-reader reliability exercise. Each video clip was evaluated according to the agreed definitions. RESULTS: Consensual definitions were developed after three Delphi rounds. Among the three selected SGs, US assessment of PGs and SMGs was agreed on. Agreement was reached to score only greyscale lesions and to focus on anechoic/hypoechoic foci in a semiquantitative matter or, if not possible on a qualitatively (present/absent) evaluation of fatty or fibrous lesions. Intrareader reliability for detecting and scoring these lesions was excellent (Cohen's kappa 0.81) and inter-reader reliability was good (Light's kappa 0.66). CONCLUSION: New definitions for developing a novel semiquantitative US score in patients with pSS were developed and tested on video clips. Inter-reader and intrareader reliabilities were good and excellent, respectively.


Assuntos
Interpretação de Imagem Assistida por Computador/normas , Glândulas Salivares/diagnóstico por imagem , Síndrome de Sjogren/diagnóstico por imagem , Ultrassonografia/normas , Consenso , Técnica Delfos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia/métodos
15.
Arthritis Res Ther ; 21(1): 59, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764862

RESUMO

OBJECTIVE: Ultrasound (US) and magnetic resonance imaging (MRI) are recommended in the diagnostic process of rheumatoid arthritis. Research on its comparability in early disease phases is scarce. Therefore, we compared synovitis and tenosynovitis detected by US and MRI on joint/tendon level. METHODS: Eight hundred forty joints and 700 tendons of 70 consecutive patients, presenting with inflammatory arthritis or clinically suspect arthralgia, underwent US and MRI of MCP (2-5), wrist and MTP (1-5) joints at the same day. Greyscale (GS) and power Doppler (PD) synovitis were scored according to the modified Szkudlarek method (combining synovial effusion and hypertrophy) and the recently published EULAR-OMERACT method (synovial hypertrophy regardless of the presence of effusion) on static images. US-detected tenosynovitis was scored according to the OMERACT. MRI scans were scored according to the RAMRIS. Test characteristics were calculated on joint/tendon level with MRI as reference. Cut-off for US scores were ≥ 1 and ≥ 2 and for MRI ≥ 1. RESULTS: Compared to MRI, GS synovitis according to EULAR-OMERACT (cut-off ≥ 1) had a sensitivity ranging from 29 to 75% for the different joint locations; specificity ranged from 80 to 98%. For the modified Szkudlarek method, the sensitivity was 68-91% and specificity 52-71%. PD synovitis had a sensitivity of 30-54% and specificity 97-99% compared to MRI. The sensitivity to detect GS tenosynovitis was 50-78% and the specificity 80-94%. For PD tenosynovitis, the sensitivity was 19-58% and specificity 98-100%. CONCLUSION: Current data showed that US is less sensitive than MRI in the early detection of synovitis and tenosynovitis, but resulted in only few non-specific findings. The higher sensitivity of MRI is at the expense of less accessibility and higher costs.


Assuntos
Artralgia/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagem , Articulações/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Doenças Musculoesqueléticas/diagnóstico por imagem , Tendões/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sinovite/diagnóstico por imagem , Tenossinovite/diagnóstico por imagem
16.
Arthritis Res Ther ; 20(1): 228, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30305156

RESUMO

OBJECTIVE: Musculoskeletal ultrasound (US) is frequently used in several rheumatology practices to detect subclinical inflammation in patients with joint symptoms suspected for progression to inflammatory arthritis. Evaluating the scientific basis for this specific US use, we performed this systematic literature review determining if US features of inflammation are predictive for arthritis development and which US features are of additive value to other, regularly used biomarkers. METHODS: Medical literature databases were systematically searched up to May 2017 for longitudinal studies reporting on the association between greyscale (GSUS) and Power Doppler (PDUS) abnormalities and inflammatory arthritis development in arthralgia patients. Quality of studies was assessed by two independent reviewers using a set of 18 criteria. Studies were marked high quality if scored ≥ 80.6% (which is the median score). Best-evidence synthesis was performed to determine the level of evidence (LoE). Positive and negative likelihood ratios (LR+, LR-) were determined. RESULTS: Of 3061 unique references, six fulfilled inclusion criteria (three rated high quality), of which two reported on the same cohort. Heterogeneity in arthralgia populations, various US machines and scoring systems hampered the comparability of results. LoE for GSUS as predictor was limited and moderate for PDUS; LoE for the additive value of GSUS and PDUS with other biomarkers was limited to moderate. Estimated LR+ values were mostly < 4 and LR- values > 0.5. CONCLUSIONS: Data on the value of GSUS and PDUS abnormalities for predicting inflammatory arthritis development are sparse. Although a potential benefit is not excluded, current LoE is limited to moderate. Future studies are required, preferably performed in clearly defined, well-described arthralgia populations, using standardized US acquisition protocols and scoring systems.


Assuntos
Artralgia/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagem , Doenças Musculoesqueléticas/diagnóstico por imagem , Artralgia/epidemiologia , Artrite Reumatoide/epidemiologia , Feminino , Humanos , Masculino , Doenças Musculoesqueléticas/epidemiologia , Valor Preditivo dos Testes
17.
Int J Mol Sci ; 19(8)2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30087255

RESUMO

Mesenchymal stem/stromal cells (MSCs) are stem cells of the connective tissue, possess a plastic phenotype, and are able to differentiate into various tissues. Besides their role in tissue regeneration, MSCs perform additional functions as a modulator or inhibitor of immune responses. Due to their pleiotropic function, MSCs have also gained therapeutic importance for the treatment of autoimmune diseases and for improving fracture healing and cartilage regeneration. However, the therapeutic/immunomodulatory mode of action of MSCs is largely unknown. Here, we describe that MSCs express the inhibitory receptor CTLA-4 (cytotoxic T lymphocyte antigen 4). We show that depending on the environmental conditions, MSCs express different isoforms of CTLA-4 with the secreted isoform (sCTLA-4) being the most abundant under hypoxic conditions. Furthermore, we demonstrate that the immunosuppressive function of MSCs is mediated mainly by the secretion of CTLA-4. These findings open new ways for treatment when tissue regeneration/fracture healing is difficult.


Assuntos
Antígeno CTLA-4/imunologia , Células-Tronco Mesenquimais/imunologia , Adipogenia , Antígeno CTLA-4/análise , Células Cultivadas , Humanos , Tolerância Imunológica , Células-Tronco Mesenquimais/citologia , Osteogênese
19.
Ann Rheum Dis ; 77(2): 300-308, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29191820

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. We investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints. METHODS: CD14+ cells from BM and peripheral blood (PB) of patients with RA and osteoarthritis (OA) were profiled with GeneChip microarrays. Detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and mobilisation. Cytometric profiling determined monocyte subsets of CD14++CD16-, CD14++CD16+ and CD14+CD16+ cells in BM, PB and synovial fluid (SF) and ELISAs quantified the release of activation markers into SF and serum. RESULTS: Investigation of genes differentially expressed between RA and OA monocytes with reference transcriptomes revealed gene patterns of early myeloid precursors in RA-BM and late myeloid precursors along with reduced terminal differentiation to CD14+CD16+monocytes in RA-PB. Patterns associated with tumor necrosis factor/lipopolysaccharide (TNF/LPS) stimulation were weak and more pronounced in RA-PB than RA-BM. Cytometric phenotyping of cells in BM, blood and SF disclosed differences related to monocyte subsets and confirmed the reduced frequency of terminally differentiated CD14+CD16+monocytes in RA-PB. Monocyte activation in SF was characterised by the predominance of CD14++CD16++CD163+HLA-DR+ cells and elevated concentrations of sCD14, sCD163 and S100P. CONCLUSION: Patterns of less mature and less differentiated RA-BM and RA-PB monocytes suggest increased turnover with accelerated monocytopoiesis, BM egress and migration into inflamed joints. Predominant activation in the joint indicates the action of local and primary stimuli, which may also promote adaptive immune triggering through monocytes, potentially leading to new diagnostic and therapeutic strategies.


Assuntos
Artrite Reumatoide/patologia , Medula Óssea/patologia , Articulações/patologia , Monócitos/citologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Perfilação da Expressão Gênica/métodos , Humanos , Monócitos/metabolismo , Monócitos/patologia , Osteoartrite/genética , Osteoartrite/imunologia , Osteoartrite/patologia , Líquido Sinovial/citologia
20.
Arthritis Res Ther ; 19(1): 233, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29041986

RESUMO

BACKGROUND: Valid detection of arthritis is essential in differential diagnosis of joint pain. Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) is a new imaging method that visualizes inflammation in wrist and finger joints. Objectives of this study were to compare FOI with ultrasonography (US, by gray-scale (GS) and power Doppler (PD)) and clinical examination (CE) and to estimate the predictive power of FOI for discrimination between inflammatory and non-inflammatory juvenile joint diseases. METHODS: FOI and GSUS/PDUS were performed in both hands of 76 patients with joint pain (53 with juvenile idiopathic arthritis (JIA), 23 with non-inflammatory joint diseases). Inflammation was graded by a semiquantitative score (grades 0-3) for each imaging method. Joints were defined clinically active if swollen or tender with limited range of motion. Sensitivity and specificity of FOI in three phases dependent on ICG enhancement (P1-P3) were analyzed with CE and GSUS/PDUS as reference. RESULTS: For JIA patients, FOI had an overall sensitivity of 67.3%/72.0% and a specificity of 65.0%/58.8% with GSUS/PDUS as reference; specificity was highest in P3 (GSUS 94.3%/PDUS 91.7%). FOI was more sensitive for detecting clinically active joints than GSUS/PDUS (75.2% vs 57.3%/32.5%). In patients with non-inflammatory joint diseases both FOI and US showed positive (i.e., pathological) findings (25% and 14% of joints). The predictive value for discrimination between inflammatory and non-inflammatory joint diseases was 0.79 for FOI and 0.80/0.85 for GSUS/PDUS. CONCLUSIONS: Dependent on the phase evaluated, FOI had moderate to good agreement with CE and US. Both imaging methods revealed limitations and should be interpreted cautiously. FOI may provide an additional diagnostic method in pediatric rheumatology. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00012572 . Registered 31 July 2017.


Assuntos
Artralgia/diagnóstico por imagem , Artrite Juvenil/diagnóstico por imagem , Imagem Óptica/métodos , Adolescente , Criança , Feminino , Articulações dos Dedos/diagnóstico por imagem , Fluorescência , Humanos , Verde de Indocianina , Masculino , Sensibilidade e Especificidade , Ultrassonografia Doppler , Articulação do Punho/diagnóstico por imagem
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