Clinical Parameters Of Disease Activity Research Articles

Multimodal nature of pain syndrome in patients with rheumatoid arthritis in relation to the course of the disease and clinical characteristics

Purpose of the study. To evaluate the character of pain syndrome in patients with rheumatoid arthritis in correlation with the course of the disease and comorbid pathology.Material and methods. Sixty-six patients with a verified diagnosis of RA were examined. Of them 84.9% were women (n=56) and 15.1% men (n=10). The median age was 59 [52; 63] years. Disease activity was assessed by DAS28-CRP, with a median of 5.2 [4.54; 6.0]. Patients with moderate (31.8%) and high activity (57.5%) predominated. Disease duration averaged Me 156 [93; 246] months. Seropositive RA was suffered by 89.3% of patients. The distribution by radiological stage was as follows: 2 radiological stage – 36.3% (n=24), 3 radiological stage – 30.3% (n=20), 4 radiological stage – 33.4% (n=22). Baseline anti-inflammatory therapy was taken by 84.8% of patients (n=56), genetically engineered biological drugs were received by 28.7% (n=16). To assess the multicomponent nature of pain syndrome, the following were used: Pain Detect questionnaire — to verify neuropathic pain (NP), CSI questionnaire — to verify central sensitisation (CS). The EQ-5D-3L questionnaire was used to assess quality of life, and the Charlson index was used to assess comorbid pathology. Structural changes were assessed by modified Sharpe method on hand and foot radiographs, synovium vascularisation was assessed by joint ultrasound.Results. 84.8% of patients had pain syndrome of mixed nature. NP correlated with pain intensity by VAS (rSp=0.458, p<0.001), DAS28-CRP (rSp=0.509, p<0.001), number of peripheral arthritis (rSp=0, 414, p<0.001), number of comorbidities (rSp=0.337, p=0.006), Charlson index (rSp=0.323, p=0.009), EQ-5D-3L (rSp= –0.268, p=0.031). CS–with VAS pain intensity (rSp=0.250, p=0.045), DAS28-CRP (rSp=0.251, p=0.044), number of painful joints (rSp=0.353, p=0.004), number of comorbidities (rSp=0.368, p=0.003), BMI (rSp=0.266, p=0.032), systolic blood pressure level (rSp=0.403, p<0.001), number of erosions on hand and foot radiographs (rSp= –0.299, p=0.016), EQ-5D-3L (rCp= –0.408, p<0.001). Patients with the presence of synovial vascularization by ultrasound had three-component pain in more than half of cases, and the combination of inflammatory pain and CS did not occur in them.Conclusions. 84.8% of patients had multicomponent pain, with pain associated only with clinical parameters of disease activity. Associated pathology and local chronic inflammation in the joint potentiate the development of other types of pain and have a mutual negative influence.

Increased vascular inflammation on PET/CT in psoriatic arthritis patients in comparison with controls

BackgroundPatients with psoriatic arthritis (PsA) have an increased risk of cardiovascular disease, possibly due to a chronic inflammatory state.ObjectivesThe main objective of this study was to investigate the difference in...

Red cell distribution width and neutrophil-lymphocyte ratio as inflammatory markers in patients with rheumatoid arthritis.

The aim was to study the red cell distribution width (RDW) and neutrophil-lymphocyte ratio (NLR) as inflammatory markers and their correlation with clinical disease activity parameters in patients with rheumatoid arthritis (RA). This observational cross-sectional study included 100 randomly selected patients with RA. Disease Activity Score with 28-joint counts and erythrocyte sedimentation rate (DAS28-ESR) was taken as a marker of disease activity. The diagnostic value of NLR and RDW in RA was assessed. The majority (51%) of cases showed mild disease activity. The mean NLR in cases was 3.88 ±2.59. Mean RDW was 16.25 ±2.49%. Neutrophil-lymphocyte ratio significantly correlated with ESR (p = 0.026), severity of pain (p = 0.013), osteoporosis (p = 0.014) and radiographic joint erosions (p = 0.048), but not with DAS28-ESR (p > 0.05) and C-reactive protein (CRP) (p > 0.05). Red cell distribution width showed a significant correlation only with NLR (p = 0.009). The positive predictive values of NLR and RDW for disease activity were 93.3% and 90% and the negative predictive values were 20% and 16.7% respectively. For NLR, the area under the curve (AUC) was 0.78 (p = 0.001) and at a cut-off value of 1.63, the diagnostic sensitivity was 97.7% and specificity 50%. For RDW, the AUC was 0.43 (p = 0.40) and at a cut-off value of 14.52, the diagnostic sensitivity was 70.5% and specificity 41.7%. The sensitivity and specificity of NLR were higher than those of RDW. A significant difference was seen between the AUC of NLR and RDW (p = 0.02). Neutrophil-lymphocyte ratio is a valuable inflammatory marker in patients with RA, but RDW is not useful in this regard.

Dietary Sodium, Potassium, and Sodium to Potassium Ratio in Patients With Systemic Lupus Erythematosus.

Purpose: The aim of this study was to investigate the association between dietary sodium, potassium, and sodium:potassium ratio and clinical disease activity parameters, damage accrual, and cardiovascular disease risk factors in a population of patients with systemic lupus erythematous (SLE). Research design and study sample: A cross-sectional study including a total of 280 patients was conducted (90.4% females; mean age 46.9 ± 12.85years). Data collection: The SLE Disease Activity Index (SLEDAI-2K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. A 24-hour diet recall was used to estimate dietary intake of sodium and potassium. Results: Dietary sodium intake was significantly associated with anti-dsDNA (β = -.005; 95% CI [.002 .008]; p = .001) and complement C4 level (β = -.002; 95% CI [-.003, .000]; p = .039). Dietary potassium intake was also significantly associated with complement C3 level (β = -.004; 95% CI [-.007, -.001]; p = .021). Multiple logistic regression models revealed a positive association between dietary sodium intake and the risk of having hsCRP > 3 (p = .005) and an inverse association between dietary potassium intake and the risk of having hsCRP > 3 (p = .004). Conclusions: SLE patients with higher dietary sodium and lower dietary potassium intakes had an increased risk of higher hsCRP. Dietary sodium intake was significantly associated with anti-dsDNA and complement C4 level, while dietary potassium intake was associated with complement C3 level, supporting that dietary sodium and potassium intakes might play a key role in markers related to disease activity in SLE patients.

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price

ObjectiveTo assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. MethodsRetrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. Results320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). ConclusionThe annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.

The association between IL17, fatigue and quality of life in psoriatic arthritis patients

ABSTRACT Background: Psoriatic arthritis is a chronic inflammatory condition. It impacts patients both physically and psychologically. Fatigue may be an early symptom of PsA, which impairs quality of life. Objectives: To assess serum IL-17, fatigue, quality of life and function impairment in PsA patients and to correlate them with clinical disease activity. Methods: 80 consecutive PsA patients were included. Fatigue assessed by Functional Assessment of Chronic Illness Therapy-Fatigue. Quality of life assessed by Psoriatic Arthritis Quality of Life. Functional capacity assessed by health assessment questionnaire. Disease activity assessed by Disease Activity in Psoriatic Arthritis. Serum IL-17 measured by ELISA. Results: There was significant difference in FACIT-F, PsAQOL, and HAQ (p<0.001) in different disease activity subgroups. There was statistically significant correlation of disease duration with disease activity, fatigue, reduced function capacity, and quality of life impairment (p≤0.05), while no correlation with the patients' age. There was statistically significant correlation between FACIT-F, PsAQOL, HAQ, and DAPSA scores (p<0.001). Serum IL-17 was significantly correlated with clinical parameters of disease activity, fatigue, function, and quality of life impairment (p≤0.05). Conclusion: Fatigue is a common clinical symptom in psoriatic arthritis patients. It is significantly associated with IL17, quality of life, functional impairment and disease activity.

Clinical experiences and predictors of success of treatment with vedolizumab in IBD patients: a cohort study

BackgroundVedolizumab has become a standard treatment for the inflammatory bowel diseases ulcerative colitis (UC) and Crohn’s disease (CD). However, there is an ongoing debate on the ideal individual treatment algorithms and means to predict treatment response are not routinely established.AimsWe aimed to describe our experiences with vedolizumab at a large German tertiary referral center and to identify clinical predictors of success of vedolizumab treatment.MethodsWe performed a retrospective single-center cohort study employing univariable and multivariable analyses as well as Kaplan–Meier analyses of persistence on treatment.Results36% and 35% of the patients with UC and CD, respectively, reached clinical remission after 17 weeks. Patients with lower clinical disease activity were more likely to achieve remission. The median persistence on treatment was 33 months for UC and 29 months for CD.ConclusionOur study confirms that vedolizumab is an efficient option for the treatment of UC and CD. Clinical parameters of disease activity may help to predict the success of treatment.

Metabolic Syndrome, Disease Activity, and Adipokines in Patients With Newly Diagnosed Inflammatory Joint Diseases.

To investigate metabolic syndrome (MetS), disease activity, and adipokine levels among patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA) at the time of diagnosis and after 1 year of follow-up. Patients with inflammatory joint diseases participating in the Northern Savo 2010 population-based longitudinal epidemiological study were evaluated for components of MetS (by National Cholesterol Education Program's Adult Treatment Panel III) and clinical parameters of disease activity. The adipokines adiponectin, adipsin, resistin, and leptin were measured at baseline and after 1 year of treatment with disease-modifying antirheumatic drugs. Among 176 patients, MetS was detected in 42% of RA, 36% of SpA, and 51% of UA patients. Metabolic syndrome was associated with higher disease activity as measured by patient global assessment in RA and UA patients and increased pain in RA patients. Leptin levels were increased in patients with MetS, showing a linearly increasing trend with the number of components of MetS in SpA and UA, but not in RA. In RA patients, decrease in disease activity correlated with decrease in leptin levels. Resistin did not associate with MetS, but a decrease in resistin correlated with decrease in disease activity in RA and UA. In SpA, increased adiponectin level correlated with relief in disease activity, but not with MetS. Metabolic syndrome was common in patients with newly diagnosed arthritides and associated with higher disease activity and increased leptin levels. Resistin responded to treatment of arthritis in RA and UA, leptin in RA, and adiponectin in SpA.

Improvement of conjunctival cytological grade and tear production in Ankylosing Spondylitis patients under TNF inhibitors: a long-term follow-up

Dry eye disease can compromise the patient’s quality of life. Few studies assessed the ocular surface (OS) in Ankylosing Spondylitis (AS) patients. This study aimed to evaluate the clinical and cytological findings of the OS in patients with AS, classify dry eye disease (DED) severity grade and conjunctival impression cytology (IC), and the effects of TNF inhibitors (TNFi) in a one-year follow-up. A baseline (BL) evaluation included 36 AS patients and 39 healthy controls. They fulfilled the Ocular Surface Index Disease questionnaire and underwent the Schirmer I test, break-up time, vital staining, and conjunctival IC. A DED severity grade, as well as IC rating, was applied. Fourteen of these patients received TNFi and analysis of ocular and systemic AS disease parameters occurred at BL and three months (3 M), and 12 months (12 M) after treatment. The AS patients presented a higher frequency of DED (p = 0.01), a worse score of severity (p = 0.001), and a higher frequency of altered IC (p = 0.007) when compared to controls. The 14 patients under TNFi presented an improvement in all the clinical disease activity parameters throughout the one-year treatment (p < 0.05) even as a concomitant increase in the Schirmer test (p = 0.04), and a significant amelioration in the altered IC to a normal IC (p = 0.006). DED is a frequent and under-diagnosed ocular disease in AS patients. The long-term parallel improvement of disease activity and OS parameters in AS patients receiving TNFi suggests that the OS can be an additional target of systemic inflammation in AS.

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price.

To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.

Association of interleukin-17 with peripheral spondyloarthropathic changes detected by musculoskeletal ultrasound in psoriatic patients

Aim of the workTo evaluate potential role of musculoskeletal ultrasound (MSUS) in detection of early peripheral spondyloarthropathic changes in psoriatic patients correlating these changes with serum interleukin-17 (IL-17) level. Patients and methodsStudy included 52 psoriatic patients and 30 matched healthy controls. Patients were assessed by modified Ritchie articular index (mRAI) and modified health assessment questionnaire (MHAQ). Serum IL-17 was measured and joints assessed by MSUS. Enthesopathy was scored using Madrid Sonographic Enthesitis Index (MASEI). ResultsPatients were 22 females and 30 males with a mean age of 41.5 ± 7.1 years and the mean duration of psoriatic skin lesion of 11.4 ± 6.9 years. Ten patients (19.2%) had rheumatic complaint while 42 (80.8%) had not. Serum IL-17 was found to be significantly increased in psoriatic patients (122.3 ± 238.9 pg/ml) compared to the controls (16.5 ± 4.6 pg/ml) (p < 0.001), and also in patients with rheumatic complaint (465.8 ± 441.1 pg/ml) than those without (50.4 ± 41.1 pg/ml). IL-17 significantly correlated with clinical parameters of disease activity, but not with the acute phase reactants. Abnormal US findings documented enthesopathy in 86.5% of patients (which was clinically detected only in 17.3%) while arthritis was found in 38.5% of the patients. There was a significant correlation between serum IL-17 levels and MASEI (total, erosion and calcification scores). ConclusionMSUS proved valuable, simple and non-invasive tool in early detection of enthesopathy and subclinical arthritis in psoriatic patients. Association of elevated serum level of IL-17 with MSUS findings clarifies its potential role in developing musculoskeletal complaints in psoriatic patients.

Facilitating patient-centered care: the development of illustrated multidimensional patient-reported outcome measures for children/adolescents with juvenile idiopathic arthritis.

To assess the validity, reliability, comprehensibility, and responsiveness to change of an illustrated child/parent multidimensional patient-reported outcome measures (PROMs) questionnaire which can assess construct outcome measures of children with juvenile inflammatory arthritis. A total of 122 children with juvenile idiopathic arthritis were included in this work in a multicenter study. The questionnaire included seven categories: (1) functional ability; (2) health-related quality of life; (3) disease activity measures: pain, global assessment, fatigue, and morning stiffness; (4) self-reported joint tenderness; (5) current medication, side effects, and adherence to therapy; (6) comorbidities; and (7) patient motivation. All the items were supported by illustrations to provide children with a visual impression of what was meant by the questions. The questionnaire has parent and patient versions. The disease activity status was assessed using JADAS-27. The questionnaire was reliable as demonstrated by a high-standardized alpha (0.890-0.978). The questionnaire items correlated significantly (p < 0.01) with clinical parameters of disease activity. The patient-reported tender joints correlated significantly with the physician's scores (0.842). Changes in functional disability, quality of life, and the motivation score showed significant variation (p < 0.01) with disease activity status in response to therapy. The illustrated PROMs questionnaire showed also a high degree of comprehensibility (9.6). Integrating PROMs into standard clinical practice is feasible and applicable. The illustrated questionnaire was valid and reliable. It provides an informative, quantitative measure for the disease activity score set data, and in the meantime, facilitates the assessment of the children's adherence to therapy, comorbidities, and motivation on an individual basis.

Matrix metalloproteinase-3 levels in relation to disease activity and radiological progression in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory and systemic disease of unknown etiology that primarily affects synovial joints and involves progressive destruction around the joints. Inflammation starting in the joint synovium causes the destruction of cartilage, bone and other adjacent tissues with pannus formation. The aim of this study was to evaluate serum matrix metalloproteinase-3 (MMP-3) levels and their clinical and radiological significance in patients with rheumatoid arthritis. The study included 59 patients with RA and 30 healthy controls. Serum MMP-3 levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Patients with a Disease Activity Score 28 (DAS28) ≤3.2 were categorized as having lower disease activity, while a DAS28 score >3.2 indicated patients with moderate/high disease activity. Additionally, the patients were divided into 2 groups in terms of disease duration: early RA (disease duration ≤2 years) and established RA (disease duration ≥2 years). Functional disability was evaluated using the Health Assessment Questionnaire (HAQ) and Nottingham Health Profile (NHP). Radiographs were scored using modified Larsen scoring. Serum MMP-3 levels in patients with RA were significantly higher than in controls (p = 0.001). Serum MMP-3 levels were correlated with laboratory and clinical parameters of disease activity, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), DAS28, and HAQ score; the exceptions were rheumatoid factor (RF) and cyclic citrullinated peptides (CCP). The serum MMP-3 levels of RA patients with moderate/high disease activity were found to be significantly higher than those of the patients with low disease activity (p < 0.001). However, MMP-3 levels were found to be similar in both established and early RA patients (p = 0.927). Additionally, the modified Larsen scores, which indicate structural damage, correlated significantly with serum MMP-3 levels (p = 0.001). These results indicate that serum MMP-3 levels may be used as an indicator for structural damage such as erosions in the early stages of the disease, and to monitor disease activity.

Decrease in 14-3-3η protein levels is correlated with improvement in disease activity in patients with rheumatoid arthritis treated with Tofacitinib

14-3-3η protein is a proinflammatory mediator that may represent a novel diagnostic and prognostic biomarker for rheumatoid arthritis (RA). We assessed the correlation between changes in serum 14-3-3η levels and changes in clinical disease activity measures in RA patients treated with Tofacitinib (TOF). Paired serum samples from 35 patients with RA were obtained at baseline and 5 months after the initiation of treatment with TOF. The levels of 14-3-3η were measured by JOINT stat 14-3-3η ELISA test kits (Augurex Life Sciences Corp.). The cut-off was defined as 0.19 ng/ml. 14-3-3η positivity was found in 57% of the patients at baseline and in 37% of the patients after 5 months of treatment. Mean ± SD baseline 14-3-3η levels [4.92 ± 8.86 ng/ml] were significantly higher (p < 0.005) than 14-3-3η levels following treatment [1.97 ± 4.59 ng/ml]. A statistically significant improvement (p < 0.001) of CDAI, SDAI, DAS4ESR and DAS4CRP was achieved after 5 month of treatment. Decrease in 14-3-3η protein levels was highly correlated with improvement in DAS4ESR (r = 0.50, p < 0.01), DAS4CRP (r = 0.46, p < 0.01) and ESR (r = 0.36, p = 0.03) and moderately correlated with improvement in CDAI (r = 0.32, p = 0.065) and SDAI (r = 0.33, p = 0.051). The correlation between decrease in 14-3-3η levels and improvement in DAS4ESR remained significant in a partial correlation analysis controlling for ESR (r = 0.39, p = 0.02). This study demonstrates that in RA patients who were treated with TOF, decrease in 14-3-3η levels is correlated with improvement in clinical disease activity parameters. The 14-3-3η protein may serve as an objective biomarker for monitoring of TOF therapy response.

Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota.

Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells

BackgroundThe peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).MethodsPB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy. Receptors for osteoclastogenic factors (CD115 and receptor activator of nuclear factor-κB [RANK]) and selected chemokines (CC chemokine receptor 1 [CCR1], CCR2, CCR4, CXC chemokine receptor 3 [CXCR3], CXCR4) were determined in an OCP-rich subpopulation (CD3−CD19−CD56−CD11b+CD14+) by flow cytometry. In parallel, levels of CC chemokine ligand 2 (CCL2), CCL3, CCL4, CCL5, CXC chemokine ligand 9 (CXCL9), CXCL10, and CXCL12 were measured using cytometric bead array or enzyme-linked immunosorbent assay. Sorted OCPs were stimulated in culture by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand, and they were differentiated into mature osteoclasts that resorb bone. Selected chemokines (CCL2, CCL5, CXCL10, and CXCL12) were tested for their osteoclastogenic and chemotactic effects on circulatory OCPs in vitro.ResultsThe OCP population was moderately enlarged among PB cells in RA and correlated with levels of tumor necrosis factor-α (TNF-α), rheumatoid factor, CCL2, and CCL5. Compared with PB, the RANK+ subpopulation was expanded in SF and correlated with the number of tender joints. Patients with PsA could be distinguished by increased RANK expression rather than total OCP population. OCPs from patients with arthritis had higher expression of CCR1, CCR2, CCR4, CXCR3, and CXCR4. In parallel, patients with RA had increased levels of CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10, with significant elevation in SF vs PB for CXCL10. The subset expressing CXCR4 positively correlated with TNF-α, bone resorption marker, and rheumatoid factor, and it was reduced in patients treated with disease-modifying antirheumatic drugs. The CCR4+ subset showed a significant negative trend during anti-TNF treatment. CCL2, CCL5, and CXCL10 had similar osteoclastogenic effects, with CCL5 showing the greatest chemotactic action on OCPs.ConclusionsIn our study, we identified distinct effects of selected chemokines on stimulation of OCP mobilization, tissue homing, and maturation. Novel insights into migratory behaviors and functional properties of circulatory OCPs in response to chemotactic signals could open ways to new therapeutic targets in RA.

Alterations of Gut Microbiome in Rheumatoid Arthritis

Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Recent studies have indicated that the pathogenesis of RA requires the interaction between genetic and environmental factors, such as gut microbiome. However, current evidence for the alterations of gut microbiome in RA is still limited. Thus, our study aimed to analyze the fecal samples from a cohort patient with RA and to identify the associated alterations in gut microbiome when compared to healthy controls. Methods: Fecal samples were obtained from treatment-naïve RA patients (n=50) and healthy controls (n=50). High-quality 16S rDNA V3–V4 sequences were extracted from fecal samples and further sequenced on a 454 Genome Sequencer platform for bioinformatics analysis, resulting in operational taxonomic units (OTUs) related to gut microbiota and phylogenetic tree. Clinical parameters of RA were correlated with specific microbial taxa by Correlation analysis. Results: A total of 121227 OTUs was clustered at 97 % sequence similarity and assigned taxonomic lineages by comparison with the Ribosomal Database Project database. The OTUs were classified into 35 phylums, 73 classes, 143 orders, 280 families, and 1165 genus. Intriguingly, our data revealed a lower alpha diversity, including richness, evenness and Shannon Index, as well as a lower Firmicutes / Bacteroidetes ratio in the gut microbiome of RA patients when compared with the healthy controls (Figure 1a, b). Moreover, at genus level, our taxonomic analysis identified 288 differentially abundant taxa (P< 0.05) (Figure 2a), among which 6 taxa, including Bacteroides, Parabacteroides, Paraprevotella, Porphyromonadaceae, Phascolarctobacterium and Carnobacterium, were significantly enriched in the gut microbiome of RA patients (Figure 2b, c). Conversely, a series of butyrate-producing taxa such as Faecalibacterium, Roseburia, Subdoligranulum, Ruminococcus and Pseudobutyrivibrio were depleted in RA patients but enriched in healthy controls (Figure 2b, c). Furthermore, we found a negative correlation (P<0.05) between the abundance of butyrate-producing Roseburia and the clinical parameters of disease status and activity such as erythrocyte sedimentation rate and the blood level of rheumatoid factors (IgM) (Figure 3). Conclusions: In the present study, we demonstrated that the composition of the gut microbiome in RA patients differed from that in healthy individuals. Our results revealed a decreased microbial diversity accompanied by altered microbial abundance in the gut microbiome of RA patients, which could be characterized as ‘dysbiosis’ and associated with the disease status and activity. The identified alterations in the gut microbiome might provide an updated overview for postulating molecular understandings and therapeutic strategy in RA.Figure 2. Differentially abundant gut microbiome in RA patients. (a) Data of phylogenetic tree analysis to identify differentially abundant taxa. (b) Percentage of 16S reads of major genus of the gut microbiota of RA patients and controls. (c) Quantification of differentially abundant genus of gut microbiome in RA and Control groups.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3. Abundance of Roseburia negatively correlated with the clinical parameters of disease activity in RA patients. Upper pannel: Correlation analysis of the 16S reads number of Roseburia and the erythrocyte sedimentation rate (ESR) in RA patients. Lower pannel: Correlation analysis of the 16S reads number of Roseburia and the blood level of rheumatoid factors (IgM) in RA patients. Note: Pearson rank correlation test was performed to determine correlations in the study variables.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The predictive value of serum S100A9 and response to etanercept is not confirmed in a large UK rheumatoid arthritis cohort.

Objective. The aim was to correlate protein concentrations of S100A9 in pretreatment serum samples with response to the tumour-necrosis factor (TNF) inhibitor drugs etanercept in a large UK replication cohort. Methods. Pretreatment serum samples from patients with RA (n = 236) about to commence treatment with etanercept had S100A9 serum concentration measured using an ELISA. Following the experimental procedure, S100A9 concentrations were analysed with respect to EULAR response. Results. No evidence of association between S100A9 concentration and EULAR response to the TNF-inhibitor biologic drug etanercept was observed following multinomial logistic regression analysis (non-responder vs moderate responder, P = 0.957; and non-responder vs good responder, P = 0.316). Furthermore, no significant associations were observed when correlating pretreatment S100A9 concentrations with clinical parameters of disease activity (P > 0.05). Conclusion. In the largest replication cohort conducted to date, no evidence for association was observed to support the use of S100A9 as a clinical biomarker predictive of response to the TNF-inhibitor biologic drug etanercept.

Lipocalin 2 as a clinical significance in rheumatoid arthritis

Aim of the studyIn this study, serum lipokalin 2 (LCN-2) levels and its clinical and radiological significance in patients with rheumatoid arthritis was evaluated.Material and methodsThe study enrolled 37 patients with RA and 34 healthy controls. Serum LCN-2 level was measured using ELISA method. Patients with DAS 28 scores ≤ 3.2, and > 3.2 were allocated into lower and high/moderate disease activity groups, respectively. Additionally patients were divided into 2 groups as early RA (disease duration ≤ 2 years) and established RA (duration of the disease ≥ 2 years). Functional disability was evaluated using Health Assessment Questionnaire (HAQ). Radiographs were scored using the modified Larsen score.ResultsSerum LCN-2 (p = 0.029) levels were significantly higher in patients with RA than in the controls. Serum LCN-2 level did not correlate with laboratory and clinical parameters of disease activity like erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), DAS 28, Health Assessment Questionnaire Score (HAQ) and Nottingham Health Profile (NHP). Similarly, any correlation could not be found between structural joint damage and serum LCN2 levels.ConclusionsThese results indicate that serum LCN-2 levels may be used as an indicator for structural damage like erosions in the early stage of the disease but do not able to be used to monitor disease activity.

Is 4-Hydroxynonenal a Predictive Parameter for the Development of Joint Erosion in Patients With Rheumatoid Arthritis?

This study aims to evaluate serum 4-hydroxynonenal (4-HNE) levels and its clinical and radiological significance in patients with rheumatoid arthritis (RA). The study included 40 patients (8 males, 32 females; mean age 51.4±11.2 years; range 24 to 72 years) with RA and 30 healthy controls (8 males, 32 females; mean age 53.0±11.7 years; range 24 to 72 years. Serum 4-HNE levels were measured using sandwich enzyme-linked immunosorbent assay method. Patients with disease activity score 28 ≤3.2 and >3.2 were allocated into low and high/moderate disease activity groups, respectively. Additionally, patients were divided into two groups as early RA (disease duration ≤2 years) and established RA (disease duration ≥2 years). Functional disability was evaluated using health assessment questionnaire. Radiographs were scored using the modified Larsen scoring. Serum 4-HNE levels in patients with RA were significantly higher than controls (p=0.001). Serum 4-HNE levels did not correlate with laboratory or clinical parameters of disease activity including erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, and health assessment questionnaire. Serum 4-HNE levels were higher in patients with established RA than patients with early RA (r=0.487, p=0.001). Besides, modified Larsen score which indicates structural damage correlated significantly with serum 4-HNE levels (p=0.001). These results indicate that serum 4-HNE levels may be used as an indicator for structural damage such as erosions in the early stage of RA; however, they are not efficient to monitor disease activity.