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ID PMID Title PublicationDate abstract
27896842 IL-12B Gene Polymorphisms and IL-12 p70 Serum Levels Among Patients with Rheumatoid Arthri 2017 Feb Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. IL-12 is now recognized as a critical cytokine in terms of regulating the balance between Th1 and Th2 cells. We investigated the role of single nucleotide polymorphisms (SNPs) (rs3212227 (A/C) and rs17860508 (CTCTAA/GC)) of the IL-12B gene in the genetic susceptibility to RA and in the severity of the disease. Six hundred and thirty-four Caucasian RA patients and 341 healthy matched controls were studied using PCR-RFLP method and high-resolution melting analysis. Concentration of IL-12 cytokine level in serum was evaluated using ELISA. The genotype frequency did not deviate from HWE in each examined group. Frequencies of the rs3212227 CC genotype were statistically higher in patients with RA compared with the healthy control group in both codominant and recessive models (P = 0.037; P = 0.04, respectively). The frequency of rs3212227 C allele also showed similar tendency (P = 0.07). IL-12 level in serum was significantly higher in RA group compared with control (P < 0.0001). We observed that increased IL-12 serum level was correlated with higher number of tender and swollen joints, ExRA presence and higher levels of haemoglobin, CRP and PLT. Also higher IL-12 level in serum was observed within RA patients with hypertension. Present findings indicated that IL-12p40 + 1188A/C polymorphism as well as IL-12p70 protein levels may be associated with RA in the Polish population.
28628469 Six-joint ultrasound in rheumatoid arthritis: a feasible approach for implementing ultraso 2017 Sep OBJECTIVES: Subclinical disease activity in rheumatoid arthritis (RA) detected by imaging methods is predictive for flares and damage. Lack of time is the major limitation for not screening for subclinical disease in routine practice. We aimed to determine the most feasible protocol to screen patients with no clinical disease activity by ultrasound (US). METHODS: A hundred consecutive RA patients with no clinical activity according to the physician had an US scan for 38 joints. The prevalence of power Doppler (PD) signal in each joint was determined and different combinations of joints were assessed for their ability to capture this information. The most practical combination with a good sensitivity was tested in another group of 50 RA patients. RESULTS: Having any PD signal was not linked to the disease activity parameters whereas presence of PD of ≥2 was associated with higher DAS28CRP. Sixty patients had at least one joint with PD of grade ≥2 (60%). A combination of the wrists and 2nd-3rd MCP joints bilaterally (PD-6 joints) was able to detect 45/60 (75%) cases with PD signals and 45% of the whole patient population. The correlation between PD-38 and PD-6 joints was excellent (r=0.820, p<0.0001). PD-6 joints in the 2nd cohort was also able to detect 22/50 (44%) of the whole group. CONCLUSIONS: Subclinical disease activity could be detected in 60% of RA patients when 38 joints screened by US. Limiting the screening to wrists, 2nd-3rd MCPs bilaterally was acceptable as it detected 75% of cases with subclinical disease and increased the feasibility.
27830970 Assessment of both articular synovitis and tenosynovitis by ultrasound is useful for evalu 2017 Jul OBJECTIVES: We investigated the association between hand dysfunction and ultrasound (US)-detected articular synovitis and tenosynovitis in patients with rheumatoid arthritis (RA). METHODS: Thirty RA patients were examined. In both hands of all subjects, articular synovitis and tenosynovitis were assessed by US at 22 joints and 12 tendons. Each joint and tendon was scored by gray-scale (GS) and power Doppler (PD) on a scale from 0 to 3. The sums of the GS or PD scores were used as the articular synovitis score and the tenosynovitis score. The sum of the articular synovitis and tenosynovitis scores was used as the combined US score. Hand dysfunction was evaluated by a grip-Health Assessment Questionnaire (HAQ) and visual analog scale of morning stiffness (MS-VAS). We used Spearman's correlation coefficient to determine the relationships among the US scores, the two hand dysfunction indices, and the DAS28-ESR. RESULTS: The articular synovitis scores were significantly correlated with grip-HAQ (GS: r(s) = 0.47, p = 0.009, PD: r(s) = 0.48, p = 0.006), but not with MS-VAS. The tenosynovitis scores were correlated with MS-VAS (GS: r(s) = 0.38, p = 0.039, PD: r(s) = 0.36, p = 0.053), but not with grip-HAQ. Both grip-HAQ (GS: r(s) = 0.53, p = 0.002, PD: r(s) = 0.55, p = 0.001) and the MS-VAS (GS: r(s) = 0.39, p = 0.031, PD: r(s) = 0.47, p = 0.008) were correlated with the combined US scores. CONCLUSIONS: The US scores combined with articular synovitis and tenosynovitis scores well reflect the severity of hand dysfunction in early-stage RA patients.
28832760 Meta-analysis of the association between PADI4 -92C/G polymorphism and rheumatoid arthriti 2017 Aug 17 Many studies have evaluated the correlation between peptidylarginine deiminase 4 (PADI4) -92C/G polymorphism and rheumatoid arthritis (RA), but the results remain inconclusive. Therefore, we performed a meta-analysis in the Chinese population to provide comprehensive data on the association between PADI4 -92C/G polymorphism and RA. Eligible studies published before May 2016 were identified in PubMed and Chinese databases. The strengths of these associations were assessed by pooled odds ratios (OR) and 95% confidence interval (CI). Eight studies documenting a total of 1351 RA cases and 1585 controls were included in this meta-analysis. In the overall analysis, a significant association between the PADI4 -92C/G polymorphism and RA was found in the Chinese population (G vs C: OR=1.32, 95%CI=1.02-1.71; GG+CG vs CC: OR=1.75, 95%CI=1.20-2.53). The subgroup analyses stratified by geographic area(s) and source of controls revealed significant results in South China, in hospital-based studies and population-based studies. In summary, this meta-analysis suggested that PADI4 -92C/G polymorphism may be associated with the RA incidence in the Chinese population, especially for South China. Further studies conducted on other ethnic groups are required for definite conclusions.
28884720 [Etiopathogenetic factors of peripheral neuropathic pain in rheumatoid arthritis]. 2017 AIM: To determine a neuropathic component of pain and define its causes in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: One hundred and eighty-three patients with confirmed RA, mean age 46,5±11,7 years, RA duration from 3 month to 30 years, were studied. Rheumatology, neurological, using the DN4 questionnaire, examinations and stimulation electromyography were used. Results and сonclusion. Signs of neuropathic pain (NP) assessed with the DN4 were identified in 73 (43%) patients with RA. These patients were older, had longer RA duration as well as higher clinical stage of disease and reduced functional abilities. There were no correlation between NP and disease activity. Peripheral nervous system (PNS) lesions were seen in 96% patients with NP: sensory motor neuropathy (55%), tunnel syndrome (14%), mononeuropathy (19%) and their combinations (4%), cervical myelopathy (4%). PNS lesions is the main etiopathogenetic factor of peripheral NP in RA. This finding opens new perspectives for complex treatment, including group B vitamins, of chronic pain in RA.
29457404 [Perioperative and drug management of patients with rheumatoid arthritis treated with join 2017 Nov 25 Rheumatoid arthritis (RA) is a most common inflammatory joint disease with direct invasion of joint synovial membrane, cartilage and bone. Currently, although the RA mitigation drugs are being improved continously, but these drugs only can delay the development of joint dysfunction. Total hip arthroplasty or total knee arthroplasty(THA or TKA) has become the only choices for patients with advanced RA, and the joint function and deformity of the patients after surgical treatment can be improved to some extent. However, the progression of RA has a direct effect on the long-term clinical effect of the surgery, and how to improve perioperative management, and combine the joint replacement surgery and drug therapy effectively, have become the focus of attention in clinical doctors. This article intends to summarize the current situation of domestic and foreign management of usage of pre-operative drugs, operation skills, prosthesis selection, postoperative treatment, rehabilitation and complications, so as to improve the long-term efficacy of joint replacement.
28462625 [Experience with a rheumatoid arthritis biobank: analysis of biological samples and clinic 2017 Feb INTRODUCTION: A biobank is a registry, which is suitable for the storage of biological samples (e.g. tissues, DNA, protein), genetical abnormalities and clinical data. Several biobanks have been created worldwide, which contribute to research and the better understanding of disease pathogenesis, genetical polymorphisms. Biobanking also helps to improve the efficacy of therapies. AIM: Our purpose was to create an internet-based biobank, in which laboratory test results, genetic alterations and related disorders of rheumatoid arthritis (RA) patients can be registered. This biobank would be able to make the research easier and it can help to improve our knowledge about diseases and it can inhibit loss of data. PATIENTS AND METHOD: We have biological samples from 204 RA patients and we have entered their data in the biobank which can be found on the website http://rheuma.biobank.eu . Statistical analysis was performed by SPSS20 statistical programme. RESULTS: By the creation of biobank that contains clinical data and biological samples of 204 RA patients, we have a database which can help to improve our knowledge about the disease and help to develop new treatment strategies. CONCLUSION: Biobanking is suitable to analyze blood samples and clinical data together. Orv. Hetil., 2017, 158(7), 270-277.
27830955 Relationship between roentgenographic joint destruction in the hands and functional disord 2017 Sep OBJECTIVES: Although a relationship between joint destruction and functional disorders seems apparent in patients with rheumatoid arthritis (RA), it has not been well proven in the literature. The aims of this study were to clarify the relationship between roentgenographic joint destruction in the hands and functional disorders in patients with RA, and to explore the appropriate assessment measures for functional disorders. METHODS: Cross-sectional data of the Genant-modified Total Sharp Score (Genant-mTSS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Disabilities of the Arm, Shoulder, and Hand (DASH), and Michigan Hand Outcomes Questionnaire (MHQ) were collected from 50 consecutive RA patients and analyzed. RESULTS: HAQ-DI, DASH, and MHQ had close correlations with Genant-mTSS, with correlation coefficients of 0.69, 0.71, and -0.70, respectively, among patients with low disease activity (DAS28 < 3.2). A floor effect was observed in HAQ-DI, but neither floor nor ceiling effects were observed in DASH and MHQ. Both DASH and MHQ were strongly correlated with HAQ-DI, with correlation coefficients of 0.87 and 0.73, respectively. CONCLUSIONS: Functional disorders had significant relationships with roentgenographic joint destruction in the hands among RA patients with low disease activity. As assessment measures of functional disorders, DASH and MHQ had no floor or ceiling effects, being different from HAQ-DI.
28386762 Fatigue in Rheumatoid Arthritis. 2017 May PURPOSE OF REVIEW: The purpose of this study was to review the current information on fatigue in rheumatoid arthritis (RA). RECENT FINDINGS: Severe fatigue is common among individuals with RA and has a significant impact on quality of life (QOL). RA-related factors (e.g., inflammation, pain) are associated with greater fatigue, but other factors, such as obesity, physical inactivity, sleep disturbance, and depression, explain the majority of variation in fatigue. Medications targeting RA have little effect on fatigue. Instead, the most effective interventions seem to address non-RA-specific factors such as physical inactivity or use cognitive behavioral approaches. No recommendations have been made for tools to measure fatigue in RA, leading to potential difficulty comparing studies. Although fatigue has great impact on patients' QOL, effective interventions that are feasible for broad dissemination remain elusive. Additional multi-faceted research is needed to identify modifiable sources of fatigue. Such research would be enhanced by harmonization of fatigue measurement across studies.
28836966 Impact of midfoot and Hindfoot involvement on functional disability in Korean patients wit 2017 Aug 24 BACKGROUND: Foot involvement in rheumatoid arthritis (RA) patients has been reported to severely affect functional capacity and quality of life. We aimed to determine the impact of midfoot and hindfoot involvement on functional disability in Korean patients with RA. METHODS: We evaluated the RA involvement and deformity of three regions of the foot (forefoot, midfoot and hindfoot) and ankle using conventional radiography in Korean patients with RA. We compared the clinical features between RA patients with and without foot or ankle involvement. Using multivariable logistic regression analyses, the impact of midfoot or hindfoot involvement on functional disability in RA patients was evaluated. RESULTS: Overall, 120 patients with a median age of 48.0 [interquartile range (IQR), 37-56] years and median disease duration of 58.0 (IQR, 10-89) months were included. The prevalence of foot or ankle RA involvement was 74 (61.7%). The number of patients with forefoot, midfoot, hindfoot and ankle involvement was 32 (43.2%), 24 (32.4%), 46 (62.2%) and 4 (5.4%), respectively. Compared to patients without foot or ankle involvement those with such involvement had greater disease activity and functional disability, more of them were treated with biologic agents, and they had a lower health-related quality of life. After adjusting for potential confounders, hindfoot involvement was associated with a higher degree of functional disability. However, walking difficulty was more associated with midfoot involvement rather than with involvement in other regions. CONCLUSIONS: In Korean patients with RA, hindfoot involvement is associated with functional disability and midfoot involvement affects walking.
29151046 The association between gastro-oesophageal reflux disease and subsequent rheumatoid arthri 2017 Nov 17 OBJECTIVE: Gastro-oesophageal reflux disease (GORD) is a common comorbidity among patients with rheumatoid arthritis (RA). While GORD has been attributed to the antirheumatic medications, no studies of human cohorts have investigated a link between GORD and RA. This study investigates whether GORD is associated with a subsequent RA diagnosis over a 5-year follow-up using a population-based dataset. SETTING: Taiwan PARTICIPANTS: We used data from the Taiwan Longitudinal Health Insurance Database. The study group consisted of 13 645 patients with an ambulatory claim showing a GORD diagnosis. We used propensity score matching to select 13 645 comparison patients (one per study patient with GORD). INTERVENTION: We tracked each patient's claims over a 5-year period to identify those who subsequently received a diagnosis of RA. Cox proportional hazard (PH) regression modelling was used for analysis. RESULTS: Over 5-year follow-up, RA incidence rate per 1000 person-years was 2.81 among patients with GORD and 0.84 among the comparison group. Cox PH modelling showed that GORD was independently associated with a 2.84-fold increased risk of RA (95% CI 2.09 to 3.85) over 5-year follow-up, after adjusting for the number of ambulatory care visits within the year following the index date (to mitigate surveillance bias). CONCLUSIONS: We observed that GORD might associate with subsequent RA occurrence. Because current treatment guidelines for RA emphasise early diagnosis and prompt treatment, the observed association between GORD and RA may help acquaint clinicians to patients with GORD with higher RA risk and facilitate early diagnosis and treatment.
28877097 Application of Transcranial Color Doppler Ultrasonography for Assessing Middle Cerebral Ar 2017 Dec To assess the role of ultrasonography for assessing middle cerebral arteries (MCAs) in rheumatoid arthritis (RA). Middle cerebral arteries of 32 RA patients and 32 healthy volunteers were examined by ultrasonography. Peak systolic blood flow velocity (PSV), end-diastolic velocity, and resistance index (RI) of MCA were measured using Doppler ultrasound. Results were expressed as mean ± SD. No significant difference in peak systolic velocity was obtained between RA patients (52.44 ± 19.56 cm/s) and healthy volunteers (51.59 ± 16.83 cm/s, P > 0.05). End-diastolic velocity in RA patients was significantly lower (15.41 ± 5.44 cm/s vs 24.54 ± 8.45 cm/s, P < 0.01) and RI markedly higher (0.66 ± 0.10 vs 0.60 ± 0.06, P < 0.05) compared with control values. Resistance index in 32 RA patients increased with disease duration (2 months to 31 years), from a median value of 0.350 to 0.830; there was a strong correlation between RI and disease duration (r = 0.965, P < 0.05). A point of 0.64 in receiver operating characteristic curve was chosen as the cutoff point, and the area under the curve was 0.918. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 90.6%, 87.5%,87.9%, 90.3%, and 89.1%, respectively. Color Doppler ultrasound in RA patients with hemodynamic changes of MCAs could be a relatively sensitive tool for the detection of cerebral atherosclerotic lesions. This could enable timely intervention for early clinical reference.
28094757 Which joints and why do rheumatologists scan in rheumatoid arthritis by ultrasonography? A 2017 May OBJECTIVES: Ultrasonography (US) has been demonstrated to improve assessment of synovitis and disease activity in rheumatoid arthritis (RA). However, the utility and feasibility of US in RA in clinical practice in real life is not known. We aimed to investigate: i) the indications for performing US in RA in daily practice; and ii) whether the number of scanned joints varies according to the purpose. METHODS: Consecutive patients who had a US scan either for diagnosis or follow-up for RA from 5 centres were recruited. The sonographers were asked to mark the joints that had a US scan and grade their findings. Descriptive analysis was applied to find out the sites and the number of joints scanned and compared according to the indications of US. RESULTS: Two hundred consecutive patients were recruited. The most common indication was assessing disease activity (48.5%) followed by diagnosis (45.5 %). Wrists (66%) and MCPs (63.5) were the most frequently scanned joints followed by knees (26%), PIPs (20%). The number of joints scanned by US was significantly higher when performed for diagnostic purposes as compared to assessing disease activity and guidance for injections (p=0.001). CONCLUSIONS: The current data highlight differences between the numbers of joints for which that the clinician feels necessary to perform US in real life. This observation may be a guide when providing recommendations regarding which joints need to be scanned according to the indication.
28986097 Effects of lentivirus-mediated ornithine decarboxylase gene on the proliferation and apopt 2018 Feb 1 OBJECTIVE: This study aimed to explore the effects of lentivirus-mediated ornithine decarboxylase (ODC) gene on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) in rats with rheumatoid arthritis (RA). METHODS: Twenty Lewis rats were randomized into control group (ten rats without processing) and RA group (ten rats of adjuvant-induced arthritis). The third-generation FLSs were randomized into test, control and blank groups. MTT assay and flow cytometry were employed to detect cell proliferation and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), and interleukin-2 (IL-2). RESULTS: Lewis rats in the RA group became ill from 11days on and got seriously ill 18days after modeling. However, rats in the control group had no obvious change. MTT assay showed that the test group had higher cell proliferation than the blank and control groups (P(1)<0.001; P(2)<0.001). Flow cytometry revealed that the apoptosis of FLSs in the test group was significantly lower than that in the blank and control groups (P(1)<0.001; P(2)<0.001). ELISA showed that the test group had higher TNF-α, IFN-γ and IL-2 level than the control and blank groups (all P<0.001), but no significant difference was found between the control and blank groups (all P>0.05). CONCLUSION: The results indicated that overexpression of ODC gene promotes the proliferation while suppressing apoptosis of FLSs in rats with RA.
28352114 Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 s 2017 Mar 28 BTK plays a critical role in the B cell receptor mediated inflammatory signaling in the rheumatoid arthritis (RA). Through a rational design approach we discovered a highly selective and potent BTK kinase inhibitor (CHMFL-BTK-11) which exerted its inhibitory efficacy through a covalent bond with BTK Cys481. CHMFL-BTK-11 potently blocked the anti-IgM stimulated BCR signaling in the Ramos cell lines and isolated human primary B cells. It significantly inhibited the LPS stimulated TNF-α production in the human PBMC cells but only weakly affecting the normal PBMC cell proliferation. In the adjuvant-induced arthritis rat model, CHMFL-BTK-11 ameliorated the inflammatory response through blockage of proliferation of activated B cells, inhibition of the secretion of the inflammatory factors such as IgG1, IgG2, IgM, IL-6 and PMΦ phagocytosis, stimulation of secretion of IL-10. The high specificity of CHMFL-BTK-11 makes it a useful pharmacological tool to further detect BTK mediated signaling in the pathology of RA.
28002151 Use of Biologic Therapy in Racial Minorities With Rheumatoid Arthritis From 2 US Health Ca 2017 Jan BACKGROUND: In the United States, there is racial/ethnic disparity in the care of rheumatoid arthritis (RA), yet there are limited data regarding the impact of varied health care systems on treatment outcomes. OBJECTIVE: The aim fo this study was to compare the frequencies of use of disease-modifying antirheumatic drugs and biologic agents in racial minorities with RA in a single-payer and variable-access health systems. METHODS: Rheumatoid arthritis disease status was examined in the Ethnic Minority Rheumatoid Arthritis Consortium (EMRAC) and Veterans Affairs Rheumatoid Arthritis Registry (VARA); frequencies of prednisone and disease-modifying antirheumatic drugs and biologic agent use at enrollment were documented. Comparisons in frequencies of RA therapies between RA cohorts and white and nonwhite racial subsets were evaluated. RESULTS: The combined cohorts provided 2899 subjects for analysis (EMRAC = 943, VARA = 1956). Routine Assessment of Patient Index Data 3 and Disease Activity Score in 28 Joints scores were equivalent (cohort, racial subsets), as was biologic agent use (26% vs. 28%) between whites and nonwhites. Disease-modifying antirheumatic drug use was greater in EMRAC nonwhites compared with their white counterparts, but similar to all VARA patients (33% vs. 22% [P < 0.001], 36%, 39%, respectively). However, biologic agent use was significantly greater in EMRAC versus VARA patients (37% vs. 22%, P < 0.001). In VARA patients, there was no difference in biologic agent use among racial subsets (22% vs. 21%). In EMRAC patients, biologic agent use was greater in whites than in nonwhites (EMRAC white 45% vs. EMRAC nonwhite 33%, P < 0.001; odds ratio, 1.66) and compared with all VARA subjects (EMRAC white 45% vs. all VARA 22%, P < 0.001; odds ratio, 2.91). Younger age, advanced education, longstanding disease, and severe disease were associated with biologic agent use. CONCLUSIONS: When compared with more variable-access systems, a VA system of care that includes a single-payer insurance may afford equality in use of biologic agents among different racial subsets.
28261973 Predictors of severe radiographic progression in patients with early rheumatoid arthritis: 2017 Oct AIM: To identify predictors of severe radiographic progression in patients with early rheumatoid arthritis (ERA). METHODS: A total of 374 patients with ERA were selected from a Korean prospective cohort. Based on their annual Sharp/Van der Heijde modified score changes (ΔSHS/year), patients were classified into severe and no progression groups. Predictors of severe progression were evaluated using a multivariable logistic regression. RESULTS: After a mean follow-up duration of 4.2 years, the median (interquartile range) ΔSHS/year were 6.3 (4.4-10.2) and 0 (0-0) in the severe and no progression groups, respectively. Multivariable regression model revealed that Health Assessment Questionnaire (HAQ) score (odds ratio [OR] = 2.17), anticyclic citrullinated peptide antibody (OR = 3.44), body mass index (BMI; OR = 0.88), 6-month cumulative erythrocyte sedimentation rate (OR = 1.01) and baseline SHS (OR = 1.07) were independent predictors of severe progression. A model incorporating all five predictors satisfactorily predicted severe progression, with an area under the curve of 0.80. Baseline SHS was the predictor with the highest contribution to the predictive power of the final model (38%). CONCLUSIONS: Our predictive model composed of five clinical predictors showed high discriminative ability between severe and no radiographic progression in patients with ERA. Among them, baseline SHS was the strongest predictor. Also, low BMI in Korean patients with ERA have a high risk of severe radiographic progression, as has previously been found for Caucasians.
28992382 Arterial Inflammation Detected With (18) F-Fluorodeoxyglucose-Positron Emission Tomography 2018 Jan OBJECTIVE: In addition to traditional risk factors, excess cardiovascular disease (CVD) in rheumatoid arthritis (RA) is attributed to enhanced vascular and/or systemic inflammation. In several small studies using (18) F-fluorodeoxyglucose-positron emission tomography/computed tomography ((18) F-FDG-PET/CT) to directly assess vascular inflammation, FDG uptake was higher in RA patients than in controls. Using a substantially larger sample of RA patients, we sought to identify RA disease characteristics independently associated with vascular FDG uptake. METHODS: RA patients underwent cardiac FDG-PET/CT, with aortic inflammation assessed by quantification of FDG uptake in the ascending aorta, calculated as the mean and maximum (max) standardized uptake value (SUV) of the entire ascending aorta and of its most diseased segment (SUV MDS). Univariate and multivariable regression models were constructed to model the associations of patient characteristics with aortic FDG uptake. RESULTS: Ninety-one RA patients were scanned. In multivariable models, in addition to the independent associations of hypertension and body mass index with increased aortic FDG uptake, the prevalence of rheumatoid nodules correlated with the SUV mean and SUV MDS mean measures, while anti-cyclic citrullinated peptide (anti-CCP) antibodies correlated inversely with these measures and with the SUV max and SUV MDS max (P < 0.05). A significant association of RA disease activity with aortic FDG uptake was observed but was restricted to anti-CCP seropositivity. CONCLUSION: Traditional CV risk factors and RA disease characteristics (rheumatoid nodules and the Disease Activity Score in 28 joints using the C-reactive protein level in anti-CCP antibody-positive individuals) were independently associated with ascending aortic FDG uptake in RA patients without clinical CVD.
29191820 Monocyte alterations in rheumatoid arthritis are dominated by preterm release from bone ma 2018 Feb 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.
29166919 Similar short-term clinical response to high-dose versus low-dose methotrexate in monother 2017 Nov 22 BACKGROUND: Aiming at rapid decrease of disease activity, there has been a trend to start with higher doses of methotrexate (MTX) in patients newly diagnosed with rheumatoid arthritis (RA), both as monotherapy and in combination with other antirheumatic drugs. We aimed to study the relationship between clinical response and MTX dose as monotherapy or combination therapy in patients with early RA. METHODS: Disease-modifying anti-rheumatic drug (DMARD)-naive patients with early RA, from a large international observational database, the METEOR database, were selected if MTX was part of their initial treatment. Patients were divided into four groups: MTX monotherapy, MTX + convention synthetic (cs)DMARDs, MTX + glucocorticoids or MTX + biologic (b)DMARDs. MTX dose was dichotomized: low dose ≤10 mg/week; high dose ≥15 mg/week. Linear mixed model analyses for the Disease Activity Score (DAS), DAS in 28 joints (DAS28) and Health Assessment Questionnaire (HAQ) were performed in each medication group, with MTX dose and time as covariates. Outcomes were assessed from baseline until 3-6 months follow up. Associations were adjusted for potential confounding by indication using propensity score (PS) modelling. RESULTS: For patients starting MTX monotherapy (n = 523), MTX + csDMARDs (n = 266) or MTX + glucocorticoids (n = 615), the PS-adjusted effects of MTX dose (high versus low) on the DAS, DAS28 and HAQ were small and not clinically meaningful. Patients starting MTX + bDMARDs were disregarded due to low numbers (n =11). CONCLUSIONS: In patients newly diagnosed with RA, no clinical benefit of high compared to low initial MTX doses was found for MTX monotherapy or for MTX combination therapy with csDMARDs or glucocorticoids.