KIAA1199 Biomarker and Ultrasonographic Findings in Rheumatoid
                    Arthritis Patients and their Correlation with Disease Activity

Abstract Introduction Rheumatoid arthritis (RA) is an autoimmune disease that affects multiple joints causing joint destruction. KIAA1199 is a novel angiogenic biomarker derived from fibroblast-like synoviocytes (FLS) it has a role in acceleration and proliferation of FLS and activation of angiogenic signaling pathways leading to erosion of cartilage and bone. Musculoskeletal ultrasound (MUSU) and Power Doppler (PDUS) directly visualizing the synovial membrane vessels, which is important in providing very early information on the changes in synovitis activity during the course of the inflammatory joint disease Objective To assess the serum level of angiogenic biomarker KIAA1199 in RA patients and its correlation with MSUS, PDUS findings, and the disease activity Patients and methods: Fifty RA patients and 40 healthy control persons age and sex-matched were recruited in this study, KIAA1199 was assessed in the serum of patients and controls, MSUS and PDUS were done for the wrist, elbow, and knee joints for all RA patients Results Serum KIAA1199 level was significantly higher among RA patients 4.36±1.22 ng/dl compared to control group 2.87±0.51 ng/dl (p<0.001). There was a highly significant correlation between KIAA1199 level and DAS28 (p=0.004), and there was a significant correlation between the PDUS with KIAA1199 level and DAS28 (p=0.001, 0.002 respectively) in wrist joints Conclusion KIAA1199 is a new pathway that enhancing cell proliferation and angiogenesis. Serum KIAA1199 level may be a useful biomarker for RA activity, and therapeutic target in RA. PDUS correlates significantly with clinical findings and novel angiogenic biomarker in RA patients.

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Elevated APE1/Ref-1 Levels of Synovial Fluids in Patients with Rheumatoid Arthritis: Reflection of Disease Activity

Journal of Clinical Medicine ◽

10.3390/jcm10225324 ◽

2021 ◽

Vol 10 (22) ◽

pp. 5324

Author(s):

In Seol Yoo ◽

Yu-Ran Lee ◽

Seong Wook Kang ◽

Jinhyun Kim ◽

Hee-Kyoung Joo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Disease Activity Score ◽

Inflammatory Responses ◽

Joint Destruction ◽

Joint Inflammation ◽

Joint Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Control ◽

The Relationship

There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and synovial fluid (SF) were collected from 46 patients with RA, 45 patients with osteoarthritis (OA), and 30 healthy control (HC) patients. The concentration of APE1/Ref-1 in serum or SF was measured using the sandwich enzyme-linked immunosorbent assay (ELISA). The disease activity in RA patients was measured using the 28-joint disease activity score (DAS28). The serum APE1/Ref-1 levels in RA patients were significantly increased compared to HC and OA patients (0.44 ± 0.39 ng/mL for RA group vs. 0.19 ± 0.14 ng/mL for HC group, p < 0.05 and vs. 0.19 ± 0.11 ng/mL for OA group, p < 0.05). Likewise, the APE1/Ref-1 levels of SF in RA patients were also significantly increased compared to OA patients (0.68 ± 0.30 ng/mL for RA group vs. 0.31 ± 0.12 ng/mL for OA group, p < 0.001). The APE1/Ref-1 concentration in SF of RA patients was positively correlated with DAS28. Thus, APE1/Ref-1 may reflect the joint inflammation and be associated with disease activity in RA.

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Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666191210110826 ◽

2020 ◽

Vol 21 (8) ◽

pp. 734-740 ◽

Cited By ~ 1

Author(s):

Shou-di He ◽

Ning Tan ◽

Chen-xia Sun ◽

Kang-han Liao ◽

Hui-jun Zhu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Caspase 3 ◽

Joint Destruction ◽

Joint Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Caspase 9 ◽

Inflammatory Processes ◽

Related Proteins ◽

Local Stimulation ◽

Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

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POS1405 OPTICAL SPECTRAL TRANSMISSION (HANDSCAN) IN PATIENTS WITH PSORIATIC ARTHRITIS: FIRST DATA ON DIAGNOSTIC VALUE AND ASSOCIATIONS WITH CLINICAL AND ULTRASOUND DISEASE ACTIVITY MARKERS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3670 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 985.1-985

Author(s):

K. Triantafyllias ◽

S. Liverakos ◽

C. Noack ◽

A. Schwarting

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Disease Activity ◽

Power Doppler ◽

Patient Characteristics ◽

Diagnostic Value ◽

Control Group ◽

Spectral Transmission ◽

Grey Scale ◽

Assessment Of Disease Activity

Background:Valid assessment of disease activity leads to improvement of long-term outcomes in patients with inflammatory arthritis (1). Optical spectral transmission (OST) is a modern diagnostic tool able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with rheumatoid arthritis (RA) (commercial device: HandScan – Demcon/Hemics, The Netherlands) (2). Even though an increasing number of studies have evaluated diagnostic value of this new technology in RA patients (2,3), no data exist regarding psoriatic arthritis (PsA).Objectives:To examine for the first time the diagnostic value of OST in detecting inflammation in patients with PsA and to evaluate its relationship with disease activity markers and various epidemiological and anthropometric patient characteristics.Methods:OST-Measurements were performed in a group of PsA patients and a group of healthy controls. The difference between OST in the two groups was statistically examined and relationships of OST with clinical (tender / swollen joint counts, disease activity on a visual analogue scale) and serological disease activity markers were evaluated. Moreover, joint ultrasound (US) examinations were performed in a subgroup of PsA patients and OST associations with a Power Doppler- and a Grey Scale-US score were examined. Finally, relationships of OST with various anthropometric and epidemiologic parameters (BMI, hand-size, gender, age) were assessed.Results:We recruited 49 PsA patients [65.3% female; mean age 53.3 years (± 11.8 SD)] and 114 control subjects [77.2% female; mean age 46 years (± 12.8 SD)]. OST was statistically significantly higher in the patient group, compared to the control group [14.95 (12.04 - 17.18, IQR) vs. 10.31 (7.84 – 13.79, IQR); p<0.001]. OST correlated moderately-strongly with both examined US scores (Power Doppler-score: r = 0.5; p = 0.026 and Grey Scale-score: r = 0.52; p = 0.028). Moreover, OST showed a moderate, statistically significant association with C-reactive protein (CRP) (r = 0,298; p = 0,037). Finally, males had significantly higher OST values than females and OST associated moderately-weakly with body mass index (BMI) in the control group (rho = 0.24; p< 0.001).Conclusion:This is the first report of a possible diagnostic value of OST in patients with PsA. OST correlated with ultrasound and serological activity markers and may thus prove to be a useful tool of disease activity assessment, next to well established diagnostic modalities, such as the joint US. Correlations of OST with patient characteristics implicate the need to take also anthropometric and epidemiological patient characteristics into account when interprenting OST results in order to avoid confounding.References:[1]Katchamart W, et al. Systematic monitoring of disease activity using an outcome measure improves outcomes in rheumatoid arthritis. J Rheumatol 2010;37:1411–1415.[2]Triantafyllias, et al. Diagnostic value of optical spectral transmission in rheumatoid arthritis: associations with clinical characteristics and comparison with joint ultrasonography. J Rheumatol 2020 1;47(9):1314-1322.[3]Onna M Van, et al. Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique. Ann Rheum Dis 2016;75:511–518.Disclosure of Interests:Konstantinos Triantafyllias Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Stefanie Liverakos: None declared, Claudia Noack: None declared, Andreas Schwarting: None declared

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Arthritis and the role of endogenous glucocorticoids

Bone Research ◽

10.1038/s41413-020-00112-2 ◽

2020 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Eugenie Macfarlane ◽

Markus J. Seibel ◽

Hong Zhou

Keyword(s):

Rheumatoid Arthritis ◽

Joint Destruction ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Current Evidence ◽

Inflammatory Microenvironment ◽

Glucocorticoid Signaling ◽

Anti Inflammatory ◽

Fibroblast Like Synoviocytes

Abstract Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.

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Rheumatoid Arthritis and Fibromyalgia: A Frequent Unrelated Association Complicating Disease Management

The Journal of Rheumatology ◽

10.3899/jrheum.080366 ◽

2009 ◽

Vol 36 (1) ◽

pp. 58-62 ◽

Cited By ~ 50

Author(s):

FABIENNE COURY ◽

ARNAUD ROSSAT ◽

ALEXANDRE TEBIB ◽

MARIE-CLAUDE LETROUBLON ◽

ANNE GAGNARD ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Disease Activity Score ◽

Joint Destruction ◽

Constant Factor ◽

Joint Disease ◽

Psychosocial Characteristics ◽

Inappropriate Treatment ◽

The Relationship ◽

Worse Prognosis

ObjectiveTo assess the value of the 28-joint Disease Activity Score (DAS28) in evaluating disease activity in rheumatoid arthritis (RA) associated with fibromyalgia (FM). In this situation, because of the weight of the subjective measures included in the DAS28 equation, the patient’s status may be overestimated, leading to inappropriate treatment. We analyze the relationship between RA and FM and discuss whether the association is random or a marker of poor prognosis.MethodsA questionnaire, developed when biologic therapies were introduced, was administered and the results analyzed in a consecutive, female outpatient population including 105 patients with RA, 49 with RA and FM (RAF), and 28 with FM. Psychosocial characteristics, disease presentation, and radiographic joint destruction evaluation were compared in the 3 populations.ResultsThe presentation of RA was the same in patients with RA and RAF, but the 2 populations differed by socioprofessional characteristics, significantly higher disease activity in patients with RAF, and significantly more severe joint destruction in patients with RA. The RAF group was similar to the FM control population in socioprofessional and some physical characteristics. Regression analysis using the DAS28 measures differed significantly in the weight allowed to 28-joint counts for pain and swelling, but the constant factor was higher in patients with RAF.ConclusionDAS28 overestimated objective RA severity in patients who also had FM. The association between RA and FM does not appear to be a marker of worse prognosis, but rather a fortuitous association between the 2 diseases and one that may afford these patients some protection against joint destruction.

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Correlation of Radiographic Progression with the Cumulative Activity of Synovitis Estimated by Power Doppler Ultrasound in Rheumatoid Arthritis: Difference Between Patients Treated with Methotrexate and Those Treated with Biological Agents

The Journal of Rheumatology ◽

10.3899/jrheum.130556 ◽

2013 ◽

Vol 40 (12) ◽

pp. 1967-1976 ◽

Cited By ~ 35

Author(s):

Kei Ikeda ◽

Daiki Nakagomi ◽

Yoshie Sanayama ◽

Mieko Yamagata ◽

Ayako Okubo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Radiographic Progression ◽

Clinical Laboratory ◽

Joint Destruction ◽

Power Doppler ◽

Joint Disease ◽

Reactive Protein ◽

Tnf Antagonists ◽

The Difference ◽

Modified Total Sharp Score

Objective.Our prospective study aimed to demonstrate that the cumulative synovial power Doppler (PD) ultrasound scores correlate with radiographic progression better than conventional measures in patients with rheumatoid arthritis (RA). We also investigated the difference between antirheumatic agents.Methods.Sixty-nine patients with RA who had recently received either methotrexate (MTX; n = 23), tumor necrosis factor (TNF) antagonists (n = 28), or tocilizumab (TCZ; n = 18) were enrolled. Patients underwent clinical, laboratory, and ultrasonographic assessment at baseline, 12 weeks, and 24 weeks. Radiographic damage was evaluated using van der Heijde modified total Sharp score (TSS) at baseline and 24 weeks.Results.Fifty-seven patients continued the same treatment regimen for 24 weeks and completed the study, and 21 patients (36.8%) showed radiographic progression during the study period. In all patients, ΔTSS significantly correlated both with cumulative 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP; ρ = 0.342, p = 0.009) and cumulative total PD scores (ρ = 0.357, p = 0.006). In MTX-treated patients, cumulative total PD scores significantly correlated with ΔTSS (ρ = 0.679, p = 0.004), whereas cumulative DAS28-CRP did not (ρ = 0.487, p = 0.056). However, cumulative total PD scores did not correlate with ΔTSS in TNF antagonist–treated or TCZ-treated patients.Conclusion.Our data confirm the evidence that synovial PD activity more accurately reflects active synovial inflammation (which actually causes joint destruction) than do conventional measures in patients treated with MTX. Our data also indicate that TNF antagonists can inhibit short-term radiographic progression in the presence of active synovitis.

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P144 What is the role of musculoskeletal ultrasound in assessing disease activity of RA in pregnancy?

Rheumatology ◽

10.1093/rheumatology/keab247.140 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Charles Raine ◽

Jessica Manson ◽

Coziana Ciurtin ◽

Ian Giles

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Clinical Assessment ◽

Power Doppler ◽

Musculoskeletal Ultrasound ◽

Tender Joint Count ◽

Control Group ◽

Research Support ◽

Pregnancy And Postpartum ◽

In Pregnancy

Abstract Background/Aims In rheumatoid arthritis (RA), musculoskeletal ultrasound (MSK-US) has greater sensitivity for the detection of active disease than clinical assessment using the DAS28 score, which is prone to false elevation by a spuriously high tender joint count (TJC) and/or visual analogue score (VAS) from non-RA causes. Thus, DAS28 may correlate poorly with MSK-US findings. In pregnancy, standardised disease activity of RA comprises calculation of the modified DAS28(3)CRP score, with removal of the VAS and ESR, both of which are confounded by pregnancy, and replacement with CRP; however, it is unknown whether non-specific musculoskeletal pain and/or peripheral oedema in (especially late) pregnancy might contribute to the TJC or swollen joint count (SJC) respectively and thus render this adapted score less reliable. Therefore, we conducted this study of pregnant RA patients and controls to assess the ability of the DAS28(3)CRP to detect disease activity compared with MSK-US. Methods Pregnant RA patients were recruited from the UCLH obstetric rheumatology clinic from September 2018 to March 2020. Patients underwent clinical assessment with DAS28(3)CRP and MSK-US longitudinally through pregnancy/post-partum. A control group of age-matched non-pregnant female RA patients was recruited from general rheumatology clinics and had equivalent assessments. MSK-US was undertaken using a Logiq S8. The standard protocol comprised 22-joint assessment of hands (dorsal longitudinal and transverse views of wrists, metacarpophalangeal and proximal interphalangeal joints). Quantification of Power Doppler (PD) signal was made as per the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) US definitions. PD scores were calculated as mean scores of all joints scanned. Statistical correlations were performed in SPSS using Spearman’s rank coefficient as data were non-normally distributed. Results A total of 45 MSK-US scans of pregnant/postpartum RA patients (N = 24, mean age 34.5+-3.6) were performed and compared to a control group of non-pregnant RA patients, who were scanned once each (N = 18, mean age 32.3+-5.2; p = 0.12). In the second (T2) and third trimester (T3) and the postpartum (PP), there was a significant positive correlation between DAS28(3)CRP and PD score (T2, ρ = 0.87 (p < 0.01); T3, ρ = 0.76 (p < 0.01); PP, ρ = 0.68 (p = 0.03)). Interestingly, each of these were stronger correlations than the equivalent comparison in non-pregnant RA patients (ρ = 0.51 (p = 0.03)). TJC also significantly positively correlated with PD score in each trimester of pregnancy and postpartum, but not in non-pregnant patients; difference between correlation coefficients was statistically significant for each trimester (T1, p < 0.01; T2, p = 0.05; T3, p = 0.05). Conclusion Interestingly, we found that that DAS28(3)CRP correlates better with PD signal on MSK-US in pregnancy than in non-pregnancy. Specifically, there was significantly better correlation of the TJC with PD score. It is unclear why non-inflammatory contributors to the TJC may be less prominent in pregnancy and further investigation is warranted. Disclosure C. Raine: Grants/research support; C.R. has received research funding from UCB. J. Manson: None. C. Ciurtin: None. I. Giles: Grants/research support; IG has received an unrestricted educational grant, speaker's fees and travel fees from UCB.

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AB0837 SERUM YKL-40 LEVELS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: RELATION TO DISEASE ACTIVITY AND JOINT DESTRUCTION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2069 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1442.2-1443

Author(s):

E. Aleksandrova ◽

A. Novikov ◽

E. Luchikhina ◽

D. Karateev ◽

G. Lukina

Keyword(s):

Rheumatoid Arthritis ◽

Serum Level ◽

Disease Activity ◽

Joint Destruction ◽

Elevated Serum ◽

Serum Levels ◽

Control Group ◽

Human Cartilage ◽

Amyloid A ◽

Early Ra

Background:YKL-40 (chitinase-3-like 1 protein, human cartilage glycoprotein 39) is one of the major proteins secreted locally in the arthritic joint by activated macrophages, chondrocytes, synoviocytes and neutrophils, YKL-40 an important marker for inflammation, cartilage remodelling and synovial hyperplasia is recognized as a possible auto-antigen in rheumatoid arthritis (RA).Objectives:The aims of the study were to determine the serum level of YKL-40 in early RA and investigate his relationship with biomarkers of disease activity and joint destruction.Methods:We studied 22 patients with early RA (ACR/EULAR 2010 classification criteria); 4 males, 18 females; median and interquartile range (25th—75th percentile) of age 55,0 (43,0-64,0) years, disease duration 7,0 (5,0-11,0) months, DAS28 4,9 (4,3-5,8); 86% IgM rheumatoid factor (IgM RF) +; 91% anti-cyclic citrullinated peptide antibody (anti-CCP) +. All patients were treated with methotrexate (MTX). Three (14 %) patients received low oral doses of steroids and intra-articular injections. The control group included 22 healthy donors (HC). Radiographs were scored according to the van der Heijde-modified Sharp score. YKL-40, matrix metalloproteinase-3 (MMP-3), anti-CCP were detected using commercially available enzyme-linked immunosorbent assays (ELISA). The serum levels of IgM RF, C-reactive protein (CRP), serum amyloid A (SAA) were measured by immunonephelometry.Results:RA patients had significantly higher serum level of YKL-40 than HC (92,1; 68,5-153,1 pg/ml vs 54,0; 41,7-83,2 pg/ml, p<0.01). Serum YKL-40 concentration was positively correlated with DAS 28 (r=0,5; p<0,05), erythrocyte sedimentation rate (ESR) (r=0,5; p<0,05), CRP (r=0,8; p<0,05), SAA (r=0,6; p<0,05) and MMP-3 (r = 0,6; p<0,05). We found no relationship between the level of YKL-40 and articular radiographic changes.Conclusion:Elevated serum concentration of YKL-40 in early RA is associated with clinical and laboratory indicators of disease inflammatory activity and increased level of MMP-3 - an immunological marker of joint destruction.Disclosure of Interests:Elena Aleksandrova: None declared, Alexander Novikov: None declared, Elena Luchikhina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Consultant of: Abbvie, Biocad, Sanofi, Celgene, Dmitriy Karateev Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Lilly, Bayer, Paid instructor for: Abbvie, Pfizer, Biocad, Sanofi, Novartis, Lilly, Galina Lukina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Paid instructor for: Abbvie, Biocad, Sanofi, Celgene

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Utilization of longitudinal ultrasound measurements to quantify changes in knee joint synovial vascularity in a rabbit model of rheumatoid arthritis

10.21203/rs.3.rs-21820/v1 ◽

2020 ◽

Author(s):

Hui Liu ◽

Chao Huang ◽

Shuqiang Chen ◽

Qing Zheng ◽

Yuhong Ye ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Time Course ◽

Early Stage ◽

Power Doppler ◽

Rabbit Model ◽

Knee Joints ◽

Control Group ◽

Vascular Morphology ◽

Contrast Enhanced ◽

Positive Correlations

Abstract Objective: This study of rabbits with ovalbumin-induced arthritis (OIA), a model of rheumatoid arthritis (RA), examined the time course of changes in synovial neovascularization based on imaging from power Doppler ultrasound (PDUS) and contrast-enhanced ultrasound (CEUS).Methods: 25 male New Zealand rabbits were in the OIA group and 5 were in the control group. Both rear knee joints of all rabbits were examined using conventional US and CEUS over 16 weeks. The knee synovia of OIA rabbits were sampled by US-guided biopsy, and the expression of CD31 and VEGF were determined by immunohistochemistry. The correlation of microvessel density (CD31 positivity) and VEGF at different times was analyzed using multimodal US.Results: OIA rabbits had increased synovial expression of CD31 and VEGF from week 6 to 12 (P<0.01). During the early stage of CEUS enhancement, dot enhancement was more common on weeks 6 and 8, and strip enhancement was more common on weeks 12 and 16 (P<0.05). There were significant positive correlations of synovial CD31 and VEGF expression with PDI grade, CEUS grade, and peak intensity (PI) (P<0.05 for all).Conclusions: OIA rabbits mimicked early-stage RA at 4 to 8 weeks, middle-stage RA at 8 to 12 weeks, and late-stage RA at 12 to 16 weeks. PDI, CEUS, and PI, especially when combined with CD31 expression, accurately characterized the extent of synovial vascularization. Increased vascular morphology based on CEUS may have value for the early diagnosis of RA.

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Lipids and Atherogenic Indices Fluctuation in Rheumatoid Arthritis Patients on Long-Term Tocilizumab Treatment

Mediators of Inflammation ◽

10.1155/2018/2453265 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Fabio Cacciapaglia ◽

Maria Grazia Anelli ◽

Angela Rinaldi ◽

Marco Fornaro ◽

Giuseppe Lopalco ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Activity Index ◽

Joint Damage ◽

Joint Disease ◽

Atherogenic Index ◽

Prolonged Treatment ◽

Control Group ◽

Long Term Treatment

Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events, and the chronic inflammatory state may generate quantitative and qualitative changes in lipoprotein fractions. The anti-IL-6 receptor tocilizumab (TCZ), even if effective in inflammation and joint damage prevention, determined significant alterations to RA patients’ lipid levels in randomized controlled trials, but real-world data are lacking. We evaluated the changes in lipid fraction levels and disease activity in a longitudinal cohort of RA patients on long-term treatment with tocilizumab (TCZ) in a community setting. We retrospectively selected 40 naïve-biologic RA patients on treatment with intravenous TCZ compared to 20 RA patients on methotrexate treatment as the control group. Total cholesterol (Tot-Chol), low-density lipoproteins (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured at the baseline and at 12, 24, and 52 weeks thereafter. At the same points, 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and EULAR clinical responses were also assessed. During the first 24 weeks, we observed in TCZ-treated patients a progressive statistically significant (p<0.001) increase in Tot-Chol, LDL, HDL, and TG, which returned close to the baseline at 52 weeks. But no changes in the lipid-related CV risk indices Tot-Chol/HDL and LDL/HDL ratios and the atherogenic index (log10 TG/HDL) were detectable. Notably, we observed a statistically significant negative correlation between changes in lipid fractions and DAS28 or CDAI. The prolonged treatment with TCZ was associated to a transient increase in cholesterol’s fractions during the first 6 months of treatment, with inverse correlation to disease activity, but with no impact on surrogate lipid indices of atherogenic risk. These findings may aid clinicians in interpreting the RA patient’s lipid profile in daily clinical practice.

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