Fluorometric Imaging for Early Diagnosis and Prognosis of Rheumatoid Arthritis.
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ABSTRACT:
SUBMITTER: Lee JH
PROVIDER: S-EPMC6947695 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Fluorometric Imaging for Early Diagnosis and Prognosis of Rheumatoid Arthritis.
Lee Jeong Heon JH Jung Sang Youn SY Park G Kate GK Bao Kai K Hyun Hoon H El Fakhri Georges G Choi Hak Soo HS
Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20191201 1
Early diagnosis and monitoring of disease progress are of significant importance in the effective treatment of rheumatoid arthritis (RA), because the continuing inflammation can lead to irreversible joint damage and systemic complications. However, applying imaging modalities for the prognosis of RA remains challenging, because no tissue-specific guidelines are available to monitor the progressive course of RA. In this study, fluorometric imaging of RA is reported using bioengineered targeted ag ...[more]
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Project description:The generalization of the early rheumatoid arthritis (ERA) concept and the existence of a window of therapeutic opportunity-a time span in which the institution of a proper therapeutic method for the disease would determine clinical improvement-have set the notion that early diagnosis and treatment may modify the course of the disease. Although in several regions of the world, especially in North America and Europe, since the year 2000, a significant reduction in diagnostic delay was observed in cohorts of patients with rheumatoid arthritis (RA), probably reflecting a stronger awareness of the importance of early diagnosis, this is not a reality in Latin America (LA). LA is a region of great economic inequality, with disparities in access to the public healthcare system and limited access to private medicine, being widely difficult to obtain a specialized medical evaluation in both scenarios. This paper aims to briefly review the main difficulties in the management of ERA in LA, based on the review of the literature, on the evaluation of a survey conducted among 214 rheumatologists of LA, members of Pan-American League of Associations for Rheumatology (PANLAR) and the experience of the authors. The paper also aims to propose solutions to the difficulties in managing ERA in LA.
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Project description:OBJECTIVE:High magnetic resonance imaging (MRI)-detected inflammation is associated with greater progression and poorer outcomes in rheumatoid arthritis (RA). This analysis aimed to determine if baseline MRI inflammation was related to clinical response and remission in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) study. METHODS:AVERT was a phase IIIb, randomized, controlled trial with a 12-month, double-blind treatment period enrolling patients with early (≤2 years' duration), anti-citrullinated peptide-positive methotrexate (MTX)-naive RA. In this post hoc analysis, patients in the abatacept plus MTX (n = 114) and MTX (n = 111) arms with available MRI results were stratified into low and high baseline MRI inflammation groups based on previously developed cutoffs of synovitis and osteitis on unilateral hand-wrist contrast-enhanced MRI. Simplified Disease Activity Index (SDAI) remission (≤3.3), Clinical Disease Activity Index (CDAI) remission (≤2.8), Boolean remission, and Disease Activity Score in 28 joints using the C-reactive protein level (<2.6) were assessed. RESULTS:Overall, 100 of 225 patients (44.4%) had high baseline MRI inflammation. In patients with high baseline MRI inflammation, a significantly greater proportion achieved remission at 12 months with abatacept plus MTX versus MTX across SDAI (45.1% versus 16.3%; P = 0.0022), CDAI (47.1% versus 20.4%; P = 0.0065), and Boolean indices (39.2% versus 16.3%; P = 0.0156). In patients with low baseline MRI inflammation, remission rates were not significantly different with abatacept plus MTX versus MTX (SDAI: 39.7% versus 32.3%; P = 0.4961). CONCLUSION:In seropositive, MTX-naive patients with early RA and presence of objectively measured high inflammation by MRI, indicating poor prognosis, remission rates were higher with abatacept plus MTX treatment versus MTX.
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Project description:Psoriatic arthritis (PsA) is an inflammatory condition characterized by a strong heterogeneity and multifaceted behavior. PsA manifests in two types-axial and peripheral-which may be present at the same time. Peripheral manifestations can be further divided into the articular (arthritis) and extra-articular (i.e., enthesitis and dactylitis) subgroups. In such a complex disease, imaging is often required to characterize the type of involvement and to evaluate the radiological damage and progression of PsA. In addition, imaging plays a pivotal role in clinical practice; that is, for axial involvement. Conventional radiology has been the main standard of reference for many years. However, in recent years, there has been growing interest in different imaging modalities, such as ultrasonography (US) and magnetic resonance imaging (MRI). All these techniques play a role in the diagnosis and follow-up of patients with PsA and cover all the types of the disease. US and MRI have good sensitivities and specificities for detecting synovitis, and this may be helpful for differential diagnosis with other musculoskeletal diseases and useful in the early or preclinical phases of the disease. However, US is not useful in the diagnosis of axial PsA. In addition, other modalities have been investigated in the field of PsA imaging. Computed tomography (CT), in particular, dual energy-CT and high-resolution peripheral CT (HRpQ-CT) might play an important role in the assessment of bone damage, erosions, and new bone formation. Regarding advanced functional imaging, FDG PET/CT is another interesting technique for exploring disease activity.
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Project description:OBJECTIVE:To investigate whether signal to noise (SNR) analysis of contrast-enhanced MRI gives additional benefit for early disease detection by Magnetic Resonance Imaging (MRI) of experimental rheumatoid arthritis (RA) in a small animal model. METHODS:We applied contrast-enhanced MRI at 7T in DBA mice with or without collagen-induced arthritis (CIA). Clinical score, OMERACT RAMRIS analysis and analysis of signal to noise ratios (SNR) of regions of interest in RA bearing mice, methotrexate/methylprednisolone acetate treated RA and control animals were compared with respect to benefit for early diagnosis. RESULTS:While treated RA and control animals did not show signs of RA activity in any of the above-mentioned scoring methods at any time point analyzed, RA animals revealed characteristic signs of RA in RAMRIS at the same time point when RA was detected clinically through scoring of the paws. The MR-based SNR analysis detected signs of synovitis, the earliest indication of RA, not only in late clinical stages, but also at an early stage when little or no clinical signs of RA were present in CIA animals and RAMRIS did not allow a distinct early detection. CONCLUSION:SNR analysis of contrast-enhanced MR imaging provides additional benefit for early arthritis detection in CIA mice.
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Project description:Background/aimsTo identify the factors associated with time to diagnosis after symptom onset in patients with early rheumatoid arthritis (RA).MethodsEarly RA patients with ≤ 1 year of disease duration in the KORean Observational study Network for Arthritis (KORONA) database were included in this analysis. Patients were further divided into two groups according to the time to diagnosis from symptom onset: the early diagnosis group (time to diagnosis ≤ 1 year) and the late diagnosis group (time to diagnosis > 1 year). Using the multivariable regression model, we identified factors associated with early diagnosis.ResultsAmong 714 early RA patients, 401 patients (56.2%) and 313 patients (43.8%) were included in the early diagnosis and late diagnosis groups, respectively. The mean disease duration was 0.47 years in the early diagnosis group and 0.45 years in the late diagnosis group. In multivariable model analysis, greater age at onset (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02 to 1.05), high school education or higher (OR, 1.68; 95% CI, 1.14 to 2.47), higher income (OR, 1.48; 95% CI, 1.05 to 2.08), and initial small joint involvement (OR, 1.42; 95% CI, 1.02 to 1.98) were factors associated with early diagnosis. At diagnosis, disease activity scores using 28 joints on diagnosis (3.81 ± 1.44 vs. 3.82 ± 1.42, p = 0.92) and functional disability (0.65 ± 0.61 vs. 0.57 ± 0.62, p = 0.07) did not different between the two groups. However, hand joint erosion on X-ray (37.8% vs. 25.6%, p < 0.01) was more common in the late diagnosis group than the early diagnosis group.ConclusionOlder onset age, higher educational level and income, and initial small joint involvement were positive factors for early diagnosis of RA.
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Project description:INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease causing articular cartilage and bone destruction. Since irreversible joint destruction can be prevented by intervention at the early stages of disease, early diagnosis of RA is important. In this study, we identified new autoantibodies in the sera of patients with early (less than one year) RA. METHODS: We screened the sera of 20 RA patients with disease duration less than one year, 19 RA patients with disease duration more than five years and 23 controls on 8,268 human protein arrays. We confirmed the validity of protein array detection by ELISA assays. We then performed epitope mapping with overlapping 15-mers to analyze RA sera reactivity. RESULTS: WIBG (within BGCN homolog (Drosophila)), GABARAPL2 (GABA(A) receptor associated protein like 2) and ZNF706 (zinc finger protein 706) proteins are preferentially recognized by autoantibodies from early RA patients. Of interest, autoantibodies to WIBG are very specific for early RA. Indeed, 33% of early RA patients' sera recognize WIBG versus 5% of RA patients with disease duration more than 5 years and 2% of controls. We identified three linear peptides on WIBG GABARAPL2 and ZNF706 that are preferentially recognized by sera of early RA patients. CONCLUSIONS: We identified new autoantibodies associated with RA with disease duration less than one year. These autoantibodies could be used as diagnosis markers in RA patients.
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Project description:BackgroundThe precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying diagnosis and therapy. Additionally, there are currently no established means to predict clinical responsiveness to therapy. Immune cell activation is a critical component therefore we examined the cellular activation of peripheral blood mononuclear cells (PBMCs) in the early stages of RA, in order to develop a novel diagnostic modality.Methods and findingsPBMCs were isolated from individuals diagnosed with early RA (ERA) (n = 38), longstanding RA (n = 10), osteoarthritis (OA) (n = 19) and from healthy individuals (n = 10). PBMCs were examined for activation of 15 signaling effectors, using phosphorylation status as a measure of activation in immunophenotyped cells, by flow cytometry (phospho-flow). CD3+CD4+, CD3+CD8+ and CD20+ cells isolated from patients with ERA, RA and OA exhibited activation of multiple phospho-epitopes. ERA patient PBMCs showed a bias towards phosphorylation-activation in the CD4+ and CD20+ compartments compared to OA PBMCs, where phospho-activation was primarily observed in CD8+ cells. The ratio of phospho (p)-AKT/p-p38 was significantly elevated in patients with ERA and may have diagnostic potential. The mean fluorescent intensity (MFI) levels for p-AKT and p-H3 in CD4+, CD8+ and CD20+ T cells correlated directly with physician global assessment scores (MDGA) and DAS (disease activity score). Stratification by medications revealed that patients receiving leflunomide, systemic steroids or anti-TNF therapy had significant reductions in phospho-specific activation compared with patients not receiving these therapies. Correlative trends between medication-associated reductions in the levels of phosphorylation of specific signaling effectors and lower disease activity were observed.ConclusionsPhospho-flow analysis identified phosphorylation-activation of specific signaling effectors in the PB from patients with ERA. Notably, phosphorylation of these signaling effectors did not distinguish ERA from late RA, suggesting that the activation status of discrete cell populations is already established early in disease. However, when the ratio of MFI values for p-AKT and p-p38 is >1.5, there is a high likelihood of having a diagnosis of RA. Our results suggest that longitudinal sampling of patients undergoing therapy may result in phospho-signatures that are predictive of drug responsiveness.
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Project description:ObjectivesTo validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis.MethodsRheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2.ResultsTwo weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient.ConclusionsOur findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.
| S-EPMC5351586 | biostudies-literature