Serum substance P: an indicator of disease activity and subclinical inflammation in rheumatoid arthritis

The aim of the is study is to examine the role of serum substance P (SP) levels as a simple biomarker for rheumatoid arthritis (RA) disease activity, its correlation with other markers of disease activity, and with selected clinical parameters. The study comprised 90 RA patients and 24 healthy controls. RA activity was assessed by means of the disease activity 28-C-reactive protein (DAS28-CRP) index and ultrasound power Doppler (USPD) by the German ultrasound score based on seven joints. SP serum values were obtained by means of an ELISA commercial kit. Statistics were achieved by the Student’s t test and Spearman correlation analysis with Bonferroni correction. As a group, RA patients had significantly increased levels of SP compared with healthy controls (p?<?0.0001). SP levels correlated with DAS28-CRP (r =?0.5050, p?<?0.0001), number of tender joints (NTJ, r =?0.4668, p?<?0.0001), number of swollen joints (NSJ, r?=?0.4439, p?<?0.0001), visual analogue scale (VAS, r?=?0.5131, p?<?0.0001). However, SP did not correlate with CRP levels (r?=?0.0468, p?=?0.6613), nor with the USPD (r?=?0.1740, p?=?0.1009). Elevated serum SP is a common feature of RA patients, which also appears to correlate with clinical measurements of disease activity and with subjective clinical data (NTJ and VAS). Thus, although SP is higher in RA patients with high disease activity, it also detects subtle RA disease activity even in patients in apparent remission, which suggests its usefulness for therapeutic decisions.     

Gadolinium-enhanced MRI features of acute gouty arthritis on top of chronic gouty involvement in different joints

The aims of the current study are to describe gadolinium-enhanced MRI features of an acute flare of established gouty arthritis in different joints and to examine a possible association between serum uric acid and MRI signs indicative of ongoing inflammation and/or structural joint damage as well as association with disease characteristics and laboratory findings. Twenty-seven male patients with established chronic gout agreed to participate, mean age 47.6 years, and mean disease duration in months 43.2 (±31.8). For all patients, detailed demographic, disease characteristics, and laboratory findings were obtained and correlated with MRI findings. In 27 patients with established gout, a total of 50 MRI studies were performed of the following joints: feet joints (n?=?23), ankles (n?=?18), knees (n?=?5), and hand and wrist joints (n?=?4). MRI revealed capsular thickening in 19 patients, bone marrow edema (BME) in 15, soft tissue edema (STE) in 20, joint effusion in 21, bone erosions in 17, cartilaginous erosions in 4, and tenosynovitis in 9 cases. In 17 cases, tophaceous lesions were found. Post contrast MRI showed synovial thickening in seven cases. Positive correlations were observed between serum uric acid levels and the following MRI findings: capsular thickening (r?=?0.552, p?=?0.003), BME (r?=?0.668, p?≤?0.0001), STE (r?=?0.559, p?=?0.002), and tenosynovitis (r?=?0.513, p?=?0.006). Using MRI in chronic gout, important features can be detected like BME, minute cartilaginous erosions, and hypertrophic synovial inflammation in post contrast MR images. Serum uric acid (SUA) was positively correlated with capsular thickening, BME, STE, and tenosynovitis.     

Calprotectin levels in patients with rheumatoid arthritis to assess and association with exercise treatment

Rheumatoid arthritis (RA) is a chronic, inflammatory, and autoimmune disease that can cause permanent joint damage. In our study, we aim to analyze the change in calprotectin levels following the low-density exercise levels applied to the patients with RA. Twenty-eight patients with RA and 30 healthy controls were included in this study. To evaluate the activity of disease in RA, scores of disease activity that has increased (DAS-28) are figured. Calprotectin, nitric oxide (NO), white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) levels are tested as the laboratory evaluation. Calprotectin, NO, CRP, ESR, WBC, and RF levels were significantly higher in the patient group compared to the control group (p?<?0.01, p?<?0.001, p?<?0.01, p?<?0.01, p?<?0.01, and p?<?0.05, respectively). In correlation analysis applied to the patient group with RA, there has been determined a positive relation with calprotectin, and DAS-28, CRP, NO, RF, and WBC (p?<?0.001, p?<?0.05, p?<?0.001, p?<?0.05, and p?<?0.05, respectively). In result of the low-density exercise treatment applied to patients with RA for 8 weeks, there has been determined a significant decrease in calprotectin, DAS-28, NO, CRP, ESR, and RF levels (p?<?0.05, p?<?0.001, p?<?0.01, p?<?0.05, p?<?0.05, and p?<?0.05, respectively). As a result, a significant relation is found between RA disease activity and calprotectin levels and other inflammatory parameters. At the same time, it shows that calprotectin which is a significant indicator of local inflammation can be used as a good identifier in following up exercise treatment.     

Disease activity,handgrip strengths,and hand dexterity in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the hand joints and leading to impairment in hand functions. Evaluation of functional impairment is necessary for assessing patient’s quality of life, disease activity, and treatment outcome. To date, many scientific studies assessed the disease activity of patients with RA, but little attention has been carried out to assess these patients’ hand functions and dexterity. The purposes of this study were to determine the clinical relevance of the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), hand dexterity with the Purdue Pegboard Test (PPT), and handgrip strength and pinch strengths of RA patients and to look into their relation between each other. A prospective trial was performed in women with RA who were followed at the physical medicine and rehabilitation department of our university hospital. Eighty-two women between the ages of 18 and 70, with a diagnosis of RA according to the 2010 American College of Rheumatology/the European League Against Rheumatism (ACR/EULAR) criterion, were recruited to the study. The Disease Activity Scores were determined by using Disease Activity Score-28 (DAS-28). Handgrip strength was measured with a Jamar dynamometer, and lateral, palmar, and tip pinch strengths were measured by a pinchmeter. Hand functions were evaluated with the PPT, and functional outcomes were assessed with the QuickDASH questionnaire. The mean age of the study group was 49.27 ± 10.69 years. The average values of DAS-28 and the QuickDASH values were found to be 4.22 ± 1.28 and 38.33 ± 19.78, consecutively. High correlation was observed between DAS-28 and the QuickDASH values (p < 0.001). The mean grip strengths in both hands were significantly correlated with the QuickDASH values (p < 0.001), and also, DAS-28 values were very significantly correlated with the mean grip strength in the dominant hand (p < 0.001) and in the nondominant hand (p < 0.01). The mean lateral pinch strengths in both hands were correlated statistically significantly with DAS-28 and the QuickDASH scores (p < 0.001). The mean tip pinch strengths in both hands were correlated with DAS-28 scores, but correlation with the QuickDASH scores was seen just in the dominant hand (p < 0.05). There was no correlation between palmar pinch strengths in both hands with the DAS-28 and QuickDASH scores (p > 0.05). DAS-28 was correlated with PPT performance on the dominant hand (p < 0.05), but there was no correlation with the nondominant hand, both hands, and assembly (p > 0.05). The QuickDASH values were not correlated with all PPT performances (p > 0.05). Handgrip strengths of both hands were positively correlated with the PPT performances (p < 0.05). In conclusion, we determined that handgrip strengths were significantly related to disability and disease activity in the RA patients in our study. The QuickDASH is practical to use in clinical practice, and positively correlates with the disease activity. Dexterity measurements with PPT in the RA patient group were found practical and effective in our study. As a result, we can suggest using QuickDASH questionnaire for functional outcomes, handgrip strength measurements for assessment of hand disability and functional impairments, and also dexterity measurements even in patients with low disease activity.     

Disease severity impacts the relationship of apelin with arterial function in patients with rheumatoid arthritis

Apelin can improve arterial function by enhancing the expression of endothelial nitric oxide synthase but this effect depends markedly on endothelial integrity. We hypothesized that inflammation influences the potential impact of apelin on arterial function in rheumatoid arthritis (RA). We assessed the associations of apelin concentrations with arterial stiffness (pulse wave velocity), wave reflection (augmentation index, reflected wave pressure, and reflection magnitude), and pressure pulsatility (central systolic pressure (CSP), central pulse pressure (CPP), peripheral pulse pressure (PPP), pulse pressure amplification (PPamp), and forward wave pressure (Pf)) among 170 RA patients without cardiovascular disease. In multivariable regression models, apelin concentrations were not independently associated with arterial function measures (p?≥?0.15) in all patients. Inflammation markers were not consistently associated with apelin levels but joint deformity counts, Disease Activity Score in 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) impacted apelin-pressure pulsatility relations (interaction p?≤?0.05). In stratified analysis, apelin was associated with CSP (partial r?=???0.33, p?=?0.01), CPP (partial r?=???0.26, p?=?0.04), PPamp (partial r?=?0.27, p?=?0.03), and Pf (partial r?=???0.33, p?=?0.01) in patients without but not with joint deformities; apelin was related to CSP (partial r?=???0.24, p?=?0.05) in those with a DAS28 joint <?2.8 (median value) (partial r?=???0.24, p?=?0.05) but not ≥?2.8, and to CSP (partial r?=???0.36, p?=?0.003) in those with an erythrocyte sedimentation rate <?13 mm/h (median value) but not ≥?13 mm/h. Apelin is associated with reduced pressure pulsatility in RA patients without but not with a high inflammatory burden. A loss of apelin protective effects on arterial function may contribute to the link between RA severity and cardiovascular risk.     

Evaluation of work disability in Japanese patients with rheumatoid arthritis: from the TOMORROW study

To evaluate work disability and associated factors in patients with rheumatoid arthritis (RA) who participated in the TOMORROW study, a 10-year cohort study in Japan. Subjects in this cross-sectional analysis comprised 191 RA patients and 191 age- and sex-matched non-RA individuals. Work-related outcomes were measured using the Work Productivity and Activity Impairment questionnaire by employment status (full-time worker (FTW), employed ≥ 35 h/week; part-time worker (PTW), < 35 h/week; home worker (HW), non-employed). In addition, we assessed the EuroQol-5 Dimensions (EQ-5D) and Health Assessment Questionnaire (HAQ) to evaluate quality of life and activities of daily living. No significant differences were evident between groups in percentages of participants in each employment status (p =?0.11), percentages of absenteeism (FTW, p?=?1.00; PTW, p?=?0.29), presenteeism (FTW, p?=?0.23; PTW, p?=?0.54), overall work impairment (FTW, p?=?0.23; PTW, p?=?0.73), or percentage of activity impairment (AI) (FTW, p?=?0.62; PTW, p?=?0.60). In the HW group, percentage of AI was higher in RA patients than that in non-RA patients (p?<?0.01). Among RA patients, HW showed lower EQ-5D and higher HAQ than FTW or PTW (p?<?0.001 each). Higher disease activity was observed in HW than FTW (p <?0.01). In terms of the effect of biological disease-modifying anti-rheumatic drugs, no significant differences in work-related outcomes, health status, or daily activity were evident between users and non-users. No significant differences in employment status or work impairment were seen between RA and non-RA groups among paid workers. HW with RA showed more impaired daily activity and higher disease activity compared to working RA patients. Trial registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000003876. Registered 1 Jun 2010.     

Sensing the main health concerns in patients with established rheumatoid arthritis

The principle objective was to determine the spectrum of some health concerns that are likely to be present in patients with established rheumatoid arthritis (RA) in patients living in United Arab Emirates. One hundred and one RA patients and 82 with other arthropathies, predominantly Arab individuals, were interviewed for main health concerns while receiving antirheumatic drug therapy. All were requested to indicate and prioritize their first three concerns. Setting up the list of concerns was based on previous conclusions to the question of “What bothers you most with your disease?” Pain attributed to the disease was the predominant concern in both groups: 82% vs. 71%, p?=?NS. Pain was also prioritized by the RA patients in the first rank, n?=?52/82 patients, and surpassed its prioritization in the second and third ranks combined (63.5% vs. 36.5%, p?=?0.001). Fear of future disability came second in RA patients, 50% vs. 25.5% in the other group, p?=?0.001. Depressive feeling surprisingly was more dominant in patients with other arthropathies, 35.5% vs. 20% in RA patients, p?=?0.001. In the prioritization of concerns, the fear of disability was first ranked by 24% of RA patients compared to 8.5% by patients with other arthropathies (p?=?0.009) while the latter patients were significantly concerned about depressive feeling and fatigue compared to RA patients (7% vs. 0%, p?=?0.007 and 14.5% vs. 5%, p?=?0.04, respectively). Significant hand deformities was noticed in 25 RA patients (25%); however, only 11 of those (44.5%) indicated their fear of disability compared to the others who did not (p?=?NS, OR?=?0.73, and 95% CI 0.275–1.665). Therefore in this predominantly Arab cohort, pain is the main health concern for RA patients and patients with other arthropathies. Patients with RA are more concerned about becoming disabled, while other patients are more concerned with feeling depressed or fatigued. Those lived with phobia of disability in RA patients did that irrespective to the presence or absence of significant hand deformities.     

Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints and tendons should be assessed to predict unstable remission?

The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0–3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist–MCP–ankle–MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist–hand–ankle–MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.     

Analysis of PD-1 and Tim-3 expression on CD4<Superscript>+</Superscript> T cells of patients with rheumatoid arthritis; negative association with DAS28

Expression of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) and programmed cell death-1 (PD-1) was studied on CD4⁺ T cells of patients with rheumatoid arthritis (RA). Association of Tim-3 and PD-1 expression with disease activity of RA patients was also addressed. A total of 37 RA patients and 31 sex- and age-matched healthy controls were included in this study. Disease activity of RA patients was determined by Disease Activity Score of 28 joints scoring system (DAS28). A three-color flow cytometry method was applied to determine the frequency of Tim-3⁺/PD-1⁺/CD4⁺ T cells. To measure the cytokine production, peripheral blood mononuclear cells (PBMCs) were stimulated with PMA/ionomycin. Concentrations of IL-17, IL-10, IFN-γ, and TNF-α were measured in culture supernatants by ELISA. The frequency of PD-1⁺/CD4⁺ and Tim-3⁺/PD-1⁺/CD4⁺ T cells was significantly higher in patients with RA compared to that in controls (p?=?0.0013 and p?=?0.050, respectively). The percentage of Tim-3⁺/CD4⁺ T cells was similar in patients and controls (p?=?0.4498). The RA patients have produced significant higher levels of TNF-α, IL-17, and IFN-γ than those of healthy controls (p?=?0.0121, p?=?0.0417, and p?=?0.0478, respectively). Interestingly, an inverse correlation was found between the frequency of Tim-3⁺/CD4⁺ cells and DAS28 of RA patients (r?=???0.4696, p?=?0.0493). Similarly, the percentage of Tim-3⁺/PD-1⁺/CD4⁺ T cells was also revealed an inverse correlation with DAS28 (r?=???0.5268, p?=?0.0493). Moreover, significant positive correlations were detected between the concentrations of TNF-α (r?=?0.6418, p?=?0.0023) and IL-17 (r?=?0.4683, p?=?0.0373) with disease activity of RA patients. Our results indicate that Tim-3 and PD-1 are involved in immune dysregulation mechanisms of rheumatoid arthritis and could be considered as useful biomarkers for determination of disease activity and progression.     

Arterial stiffness is associated with left ventricular dysfunction in patients with rheumatoid arthritis

Arterial stiffness (AS) has a detrimental effect on cardiovascular system particularly on left ventricle (LV). The aim of the study was to evaluate the impact of AS on LV functions in patients with rheumatoid arthritis (RA). Forty patients with RA and 25 age-sex matched control subjects (mean age 48.5?±?6.3 vs. 45.1?±?6.9 years, respectively, p?=?0.06) were enrolled in study. AS was assessed by carotid-femoral pulse wave velocity (CF-PWV) and heart rate corrected augmentation index (AIx@75) measured by applanation tonometry (SphygmoCor). LV function was evaluated using tissue Doppler-derived myocardial performance index (MPI) from lateral mitral annulus. CF-PWV (28.3?±?10.3 vs. 21.8?±?9.3 m/s, p?=?0.03), AIx@75 (10.2?±?2.3 vs. 9.2?±?1, %, p?=?0.01) and MPI (0.46?±?0.12 vs. 0.36?±?0.1, p?<?0.001) were significantly higher in patients with RA than in controls. LV MPI was found to be significantly positive correlated with CF-PWV, AIx@75, and ESR (r?=?0.360, p?=?0.005; r?=?0.334, p?=?0.009; r?=?0.293, p?=?0.023, respectively). Arterial stiffness parameters including CF-PWV and AIx@75 are associated with subclinical left ventricular dysfunction in patients with RA.     

No predictive effect of body mass index on clinical response in patients with rheumatoid arthritis after 24 weeks of biological disease-modifying antirheumatic drugs: a single-center study

The aim of this study was to determine whether body mass index (BMI) is associated with clinical response to biologics in patients with rheumatoid arthritis (RA). We enrolled 68 patients with RA who were treated with biological disease-modifying antirheumatic drugs (bDMARDs). Biologics included abatacept, tocilizumab, and tumor necrosis factor-α (TNF-α) blockers (etanercept and adalimumab). Baseline BMI (kg/m²) was classified as normal (BMI?<?23.0), overweight (23.0?≤?BMI?<?25.0), or obese (BMI?≥?25.0). Improvement of disease activity score 28 (DAS28) and achievement of the European League Against Rheumatism (EULAR) remission and responses between baseline and 24 weeks were our measures of clinical improvement. Mean baseline BMI before treatment with bDMARDs in patients with RA was 22.2 (SD 3.6). DAS28-ESR and DAS28-CRP were significantly reduced from baseline after 24 weeks of treatment with bDMARDs (p?<?0.001 of both). ?DAS28-ESR and ?DAS28-CRP were not found among patients with normal, overweight, or obese BMI (p?=?0.133 and p?=?0.255, respectively) nor were EULAR responses or EULAR remission (p?=?0.540 and p?=?0.957, respectively). Logistic regression analysis showed no relationship of BMI with EULAR clinical responses (p?=?0.093 for good response and p?=?0.878 for EULAR remission). This study reveals that BMI is not a predictive factor of clinical response to bDMARDs in patients with RA.     

Ultrasound assessment of enthesis thickening in psoriatic arthritis patients treated with adalimumab compared to methotrexate

The objective of the study was to combine ultrasonographic (US) with clinical findings for comparing the effect of adalimumab (ADA) to methotrexate (MTX) on the thickness of tendons and enthesis in psoriatic arthritis (PsA) patients. Forty-three consecutive PsA patients were examined at baseline and after 6 and 12 weeks of treatment with ADA or MTX. The US assessment included thickness measurement of the extensor (ET) and flexor tendons (FT) of the second and third finger of both hands, plantar aponeurosis (PA) and the Achilles tendon (AT) bilaterally. Disease activity (DA) was assessed by the number of tender (TJ) and swollen joints (SJ), the number of inflamed enthesis (IE), pain assessment (PAI), and patient (PDAI) and physician (PHDAI) disease activity evaluations by visual activity score (VAS). Nineteen patients received MTX and 24 patients received ADA. All DA parameters improved in both groups. A decrease in thickness of tendons and enthesis was observed only in the ADA group, reaching a level of significance for the left AT (p?=?0.01), left PA (p?=?0.007), the second left FT (p?=?0.04) and the third ET (p?=?0.04). ADA patients showed a trend towards a better response to treatment compared to MTX patients that reach significance at week 6 of treatment for the thickness of left AT (p?=?0.04), left PA (p?=?0.03), the number of TJ (p?=?0.0136), PAI (p?=?0.0028), and PDAI (p?=?0.029). ADA treatment for PsA compared to MTX significantly improved signs of DA and several US parameters. US assessment of enthesis can be an additional useful tool in the monitoring of psoriatic enthesopathy.     

Fear of falling and foot pain,impairment and disability in rheumatoid arthritis: a case-control study

Fear of falling, foot pain, impairment and disability are commonly reported in rheumatoid arthritis (RA). However, the relationship between fear of falling and foot pain, impairment and disability has not been investigated in established RA. The aim of the study was to evaluate the relationship between fear of falling and foot pain, walking velocity and foot impairment and disability in women with established RA. A secondary aim was to evaluate differences between fear of falling, foot pain, walking velocity and foot impairment and disability in women with established RA and age- and sex-matched control participants. Twenty-one women with established RA and twenty-one age- and sex-matched controls were assessed for fear of falling, foot pain, foot impairment and disability and walking velocity. Pearson’s r-correlations were used to examine relationships between fear of falling and the foot measures. Independent samples t tests evaluated the differences in fear of falling and foot measures between the two groups. In people with RA, significant correlations were found between fear of falling and foot impairment (r?=?0.53, p?=?0.015), foot disability (r?=?0.77, p <0.001) and walking velocity (r?=?0.56, p?<?0.001). No correlation was found between fear of falling and foot pain (r?=?0.36; p?=?0.11). Significant differences between cases and control participants were found between fear of falling (p?=?0.001), foot impairment (p?=?0.004) and foot disability (p?<?0.001). Foot impairment and disability relates to fear of falling in women with established RA. A better understanding of fear of falling in people with established RA may contribute to more efficient falls assessments in order to identify at risk individuals.     

Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis

The goal of this prospective study was to assess non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) by means of non-invasive wireless capsule enteroscopy. A total of 143 patients (74 with RA, 69 with OA) treated with NSAIDs (>1 month) and 42 healthy volunteers were included. All subjects underwent capsule endoscopy, laboratory tests and filled in questionnaires. The severity of small bowel injury was graded as: mild (red spots or sporadic erosions), moderate (10–20 erosions) or severe (>20 erosions or ulcers). Capsule endoscopy identified small bowel lesions in 44.8 % of patients (mild 36.4 %, moderate 3.5 % and severe in 4.9 %). Mild non-specific lesions were found in 11.9 % healthy volunteers. There was a significantly higher prevalence of enteropathy in RA (56.8 %) compared to OA (31.9 %, p < 0.01). A significant difference between NSAID users (RA and OA) with and without enteropathy was observed in erythrocytes (p < 0.01), the leucocyte count (p < 0.05), haemoglobin (p < 0.05), haematocrit (p < 0.05), serum albumin (p < 0.01) and erythrocyte sedimentation rate (p < 0.05). No relationship was found between enteropathy and dyspepsia, gender or age. NSAID therapy is associated with a significant risk of small bowel injury. The risk is significantly higher in RA patients suggesting a possible influence of the underlying disease. Trial registration number: DRKS00004940.     

The functional <Emphasis Type="Italic">PTPN22</Emphasis> C1858T polymorphism confers risk for rheumatoid arthritis in patients from Central Mexico

Rheumatoid arthritis (RA) is a complex genetic disease. Human leukocyte antigen (HLA) and non-HLA genes are reportedly associated with an increased risk of RA. The protein tyrosine phosphatase non-receptor 22 gene (PTPN22), which encodes the lymphoid tyrosine phosphatase (LYP) protein, is one of the best examples of a non-HLA gene associated with a risk for RA in several populations. The functional PTPN22 C1858T (R620W) non-synonymous polymorphism is widely associated with an increased risk for RA in Europeans and non-Europeans. The aim of this study was to determine if the PTPN22 C1858T polymorphism confers susceptibility to RA in a sample of patients from Mexico. This study included 364 RA patients and 387 non-related controls from Central Mexico. Genotyping of the PTPN22 C1858T (rs2476601) polymorphism was performed using allelic discrimination assays with TaqMan probes. The functional PTPN22 C1858T polymorphism was associated with an increased risk for RA in our study population. The CC vs CT genotype in RA patients versus healthy controls had an odds ratio (OR) of 4.17 (95 % CI 1.79–9.74, p?=?0.00036), while T allele had an OR of 4.06 (95 % CI 1.75–9.41, p?=?0.00043). PTPN22 is a genetic risk factor for developing RA in the Mexican population.     

Association between susceptibility to rheumatoid arthritis and <Emphasis Type="Italic">PADI4</Emphasis> polymorphisms: a meta-analysis

The objective of the study was to determine by meta-analysis whether polymorphisms of the gene encoding peptidylarginine deiminase 4 (PADI4) are associated with susceptibility to rheumatoid arthritis (RA). A literature review was conducted to identify data sets that described analyses of genetic association between PADI4 polymorphisms and RA. Data sets were collated and a meta-analysis was performed, with a specific focus on associations within Caucasian and Asian populations. A total of 15,947 RA cases and 22,696 controls that were taken from 28 studies in 24 papers were included in this study. Meta-analysis showed a significant association between allele 2 of the PADI4_94 polymorphism and RA in the overall population (odds ratio [OR]?=?1.155, 95 % confidence interval [CI]?=?1.069–1.249, p?=?2.7?×?10^?5). Stratification by ethnicity revealed an association between PADI4_94 allele 2 and RA in Asians (OR?=?1.273, 95 % CI?=?1.193–1.359, p?<?1.0?×?10^?9), but not in Caucasians (OR?=?1.024, 95 % CI?=?0.973–1.078, p?=?0.358). However, meta-analysis using homozygote contrast showed an association between PADI4_94 allele 2 and RA in both Asians (OR?=?2.311, 95 % CI?=?1.1.858–2.875, p?<?1.0?×?10^?9) and Caucasians (OR?=?1.523, 95 % CI?=?1.157–2.004, p?=?0.008). Meta-analysis also revealed an association between allele 2 of the PADI4_104 polymorphism and RA in both Asians (OR?=?1.547, 95 % CI?=?1.247–1.919, p?=?7.1?×?10^?6) and Caucasians (OR?=?1.096, 95 % CI?=?1.025–1.172, p?=?0.008). Finally, meta-analysis showed an association between allele 2 of the PADI4_92 polymorphism and RA in Asians (OR?=?1.263, 95 % CI?=?1.153–1.384, p?=?5.8?×?10^?8), but not in Caucasians (OR?=?1.123, 95 % CI?=?0.980–1.287, p?=?0.095). Meta-analysis indicated no association between allele 2 of either the PADI4_90 or PADI4_89 polymorphisms and RA in Asians. This meta-analysis revealed that the PADI4_94 and PADI_104 polymorphisms are associated with susceptibility to RA in Asians and Caucasians, and that the PADI4_92 polymorphism is associated with susceptibility to RA in Asians, but not in Caucasians.     

Ultrasound-detected joint inflammation and B cell count: related variables for rituximab-treated RA patients?

This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0–3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28 < 2.6 = 34.53, DAS28 > 2.6 = 49.45, p = 0.52) and PDI score (PDI < 1 = 49.48, PDI > 1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = ?0.151, p = 0.371; r = ?0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count.     

Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens from <Emphasis Type="Italic">Proteus mirabilis</Emphasis>

Patients with rheumatoid arthritis (RA) from different ethnic groups present elevated levels of antibodies against Proteus mirabilis. This finding implicates P. mirabilis in the development of RA. The aim of this study was to investigate the importance of P. mirabilis in the etiopathogenesis of RA in Greek RA patients. In this study, 63 patients with RA and 38 healthy controls were included. Class-specific antibodies IgM, IgG, and IgA against three human cross-reactive and non-cross-reactive synthetic peptides from P. mirabilis—hemolysin (HpmB), urease C (UreC), and urease F (UreF)—were performed in all subjects, using the ELISA method. RA patients had elevated levels of IgM, IgG, and IgA antibodies against HpmB and UreC Proteus peptide which are significantly different compared to healthy controls: p = 0.005, p < 0.001, and p = 0.003 and p = 0.007, p = 0.002, and p < 0.001, correspondingly. Also, elevated levels of IgM, IgG, and IgA antibodies against the UreF Proteus peptide—which are non-cross-reactive with human tissue antigens—were observed and their significant difference compared to healthy controls (p = 0.007, p < 0.001, p < 0.001). Anti-peptide antibodies in RA patients showed a significant correlation with rheumatoid factors (Rf), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), especially when patients were divided into subgroups according to the receiving treatment. Greek RA patients present elevated levels of antibodies against P. mirabilis antigenic epitopes, such as in North European populations, albeit Greek RA patients presenting the cross-reaction antigen in a low percentage. These results indicate that P. mirabilis through the molecular mimicry mechanism leads to inflammation and damage of the joints in RA.     

Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial

Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) possesses anti-inflammatory effects, attributed to the main constituent andrographolide proposed as alternative in the treatment of autoimmune disease. A prospective, randomized, double blind, and placebo-controlled study in patients with rheumatoid arthritis (RA) was performed. Tablets (Paractin®) made of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks, after a 2-week washout period to 60 patients with active RA. The primary outcomes were pain intensity measured using a horizontal visual analog pain scale (VAPS). In addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity of joint pain decreased in the active vs placebo group at the end of treatment, although these differences were not statistically significant. A significant diminishing for week in tender joint ?0.13 95% confidence interval (CI; ?0.22 to 0.06; p?=?0.001), number of swollen joints ?0.15 95%CI (?0.29 to ?0.02; p?=?0.02), total grade of swollen joint ?0.27 95%CI (?0.48 to ?0.07; p?=?0.010), number of tender joints ?0.25 95%CI (?0.48 to ?0.02; p?=?0.033), total grade of swollen joints ?0.27 95%CI (?0.48 to ?0.07; p?=?0.01), total grade of tender joints ?0.47 95%CI (?0.77 to ?0.17; p?=?0.002) and HAQ ?0.52 95%CI (?0.82 to ?0.21; p?p?A. paniculata could be a useful “natural complement” in the treatment of AR; however, a larger trial and a more extended period of treatment is necessary in order to corroborate these results.     

Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR remission criteria: an analysis of 967 patients from two databases of early and established rheumatoid arthritis patients

The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a strict cutoff for patient global assessment (PGA, value ≤?1/10). Near-remission corresponds to remission for joint counts and C-reactive protein but with PGA?>?1. The objective was to explore whether the contribution of PGA to remission and near-remission varied according to the wording of the PGA and in relation to disease duration. In patients with early arthritis (N?=?731, French ESPOIR cohort) or established RA (N?=?236 patients from across Europe), frequency of remission versus near-remission was assessed according to the phrasing used for PGA (global health versus disease activity). In 967 patients (mean [standard deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range 12.9–16.7% (according to wording of PGA) in early RA and 6.8–7.2% in established RA. Near-remission was more frequent: 13.0–16.8% in early RA and 13.1–13.6% in established RA. The ratio of remission to near-remission was higher in the early arthritis cohort (0.8–1.3 versus 0.5–0.5 in established RA). Using the disease activity PGA led to more remission and less near-remission than the global health PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p?=?0.047) but not in established RA. The proportion of patients who can be classified as remission or near-remission differs in early RA compared to establish RA and depends upon the formulation of the PGA question. PGA referring to disease activity and not global health may be preferred in early disease, if the objective is more alignment with inflammation assessment.