Higher DAS28 Scores Research Articles

Understanding Differences in Patient Descriptions of Rheumatoid Arthritis Flares Using OMERACT Core Domains.

Recently, there has been consensus on domains that constitute flares in rheumatoid arthritis (RA); however, variations in patients' flare descriptions continue to be observed. This study evaluates how demographic and clinical characteristics influence these differences. Participants enrolled in a prospective RA registry completed a qualitative survey that included the open-ended question "What does a flare mean to you?" Responses were categorized into Outcome Measures in Rheumatology (OMERACT) core and research domains. Univariate analyses evaluated demographic and clinical characteristics. Regression analyses determined independent variables associated with flare description variations. Among 645 participants, the median Disease Activity Score in 28 joints (DAS28) with C-reactive protein was 2.1 (IQR 1.6-2.9); 58% of the participants reported at least 1 flare in the past 6 months. Participants reported a median of 3 (IQR 2-5) OMERACT domains when describing flares. Fatigue was more commonly noted among females (odds ratio [OR] 6.12; P < 0.001). Older participants were less likely to report emotional distress (OR 0.97; P = 0.03), swollen joints (OR 0.99; P = 0.04), physical function decrease (OR 0.98; P = 0.02), and a general increase in RA symptoms (OR 0.98; P = 0.005). Participants with a higher DAS28 score were less likely to report symptoms of stiffness (OR 0.70; P = 0.009), and those who experienced a flare within the last 6 months were more likely to describe flares as pain (OR 2.53; P < 0.001) and fatigue (OR 2.00; P = 0.007). Variations in patients' flare descriptions can be driven by a patient's disease activity, the experience of a recent flare, as well as different demographic characteristics, such as age and gender. Understanding the interplay of these characteristics can guide a physician's approach to the management of patients' RA flares.

Изменения микробиоты кишечника у больных ювенильным идиопатическим артритом

Currently, the issue of the relationship between gut microbiota and juvenile idiopathic arthritis (JIA) is still relevant. The study was aimed to assess alterations in the gut microbiota taxonomic composition and estimate the relationship between these alterations and cortisol, melatonin, and TNFα at the genus level in patients with JIA. The comparative cross-sectional study involved 65 patients with JIA (index group) and 60 healthy children (control group). The gut microbiota taxonomic composition and plasma levels of cortisol, melatonin, and TNFα were assessed. The following alterations of the gut microbiota taxonomic composition were found in patients with JIA: the significantly decreased abundance of Anaerostipes (р = 0.042), Lachnospira (р = 0.034), Roseburia (р = 0.002), Coprococcus (р = 0.014), Dialister (р = 0.003) and the increase in the abundance of Ruminococcus (р = 0.012). There were significant correlations of cortisol levels with the abundance of Lachnospira (r = –0.44; p = 0.001), melatonin concentrations and the abundance of Coprococcus (r = –0.48; p = 0.023), the levels of TNFα and the abundance of Ruminococcus (r = 0.52; p = 0.001). The association of the Lachnospira, Roseburia, and Ruminococcus abundance with the higher DAS28 scores was discovered (r = –0.57; p = 0.002; r = –0.44; p = 0.002; r = 0.54; p = 0.032, respectively). The findings provide additional information about the features of gut microbiota alterations and their correlation with some hormone and inflammatory biomarkers associated with JIA, that could provide the basis for further research and possibly for new approaches to treatment of this disorder.

Prevalence of Vertebral Compression Fracture Among Rheumatoid Arthritis Patients in Sulaymaniyah

Background: The risk of fractured vertebral increases in patients with rheumatoid arthritis as they are more likely to suffer from osteopenia, and osteoporosis. Objectives: This study aimed to investigating the rate and risk factors of vertebral fractures in patients with rheumatoid arthritis. Methods: We recruited 201 patients aged between 30 and 70 who attended the rheumatology department at Shahid Hemn Teaching Hospital in Sulaymaniyah, between January and September 2022. Medical records were reviewed for disease and treatment characteristics while also clinically evaluated by a rheumatologist. Spinal radiographs were assessed by two experienced radiologists blinded to patients’ clinical diagnosis and status. Compression fractures were classified by using the Genant semiquantitative method, and the type of fracture was classified as wedged fracture, biconcave fracture, or crushed fracture. Results: Of the 201 included participants, 151 were female, and 50 were male. The BMI of women was higher than men by nearly four points (P&lt;0.001). Most women were also illiterate (68/151, 45.0%) and unemployed (139/151, 92.1%). Hypertension (28.4%) and diabetes mellitus (14.4%) were the most reported comorbidities. Women were more likely to have higher DAS28 scores while men had more vertebral fractures (P=0.003). The probability of fractures increased with age, male sex, and illiteracy compared to primary school, osteopenia, and osteoporosis through simple and multiple logistic regression models. Conclusion: With at least one fracture affects females and males at a rate of 27.8% and 52.0%, respectively. Also reported that age, male sex, illiteracy, osteopenia, and osteoporosis significantly increase the risk of fractures.

The relationship between major dietary patterns and disease activity of rheumatoid arthritis.

Rheumatoid arthritis is an inflammatory illness characterized by persistent and systemic inflammation. There is just a little amount of research on nutrition and RA progression. The goal of this research is to see whether there's a link between main eating trends and RA activity. In Kermanshah, Iran, 183 individuals with RA were studied in cross-sectional research. The American College of Rheumatology's 2010 criteria were used to diagnose RA. The disease activity score 28 and nutritional information from a reliable 147-item food frequency questionnaire were used to assess RA activity. Factor analysis was used to extract dietary patterns. The researchers discovered three main eating trends, which they named. Individuals in the highest tertile of a high protein anti-inflammatory dietary pattern that emphasizes consumption of dairy products, red meats, white meats, vegetables oils, condiments, vegetables and fruits as well as low in salts and refined grain had lower DAS-28 scores than those in the first tertiles (T3=2.09±0.14 vs. T1=3.75±0.13; P-value = 0.001) after controlling for potential confounders. Patients in the top tertile of the low fiber dietary pattern had higher DAS-28 scores than those in the bottom tertile (T3=3.40±0.15 vs. T1=2.95±0.15; P-value=0.036) than those in the bottom tertile. This research found an inverse connection between RA activity and adopting a high-protein anti-inflammatory dietary pattern. Furthermore, adopting a low-fiber dietary pattern may be linked to increased RA disease activity. To confirm such a relationship, further research is needed in the future.

Geriatric syndromes among patients with rheumatoid arthritis: A comparison between young and elderly patients

In the general geriatric population, Geriatric syndromes (GSs) predict greater likelihood of hospitalization, increased health care use and cost. The present study aimed to compare GSs among young and elderly patients with rheumatoid arthritis (RA). In a cross-sectional study a total of 98 participants, including 65 elderly (≥60 years) and 33 young adult patients (<60 years) with RA who referred to the geriatric and rheumatologic clinic were enrolled. Patients were categorized into three groups (healthy elderly, n=27; elderly with RA, n=38; and young people with RA, n=33). GSs were assessed using mini-mental state exam (MMSE), five-item geriatric depression scale-15 (GDS-15), mini nutritional assessment (MNA), and asking patients about history of falls in the past year. The RA activity in patients was assessed using disease activity for rheumatoid arthritis score-28 (DAS-28) scale, serum ESR (mm/h) level. There was a statistically significant differences in terms of DAS-28 (2.23±1.01 vs. 0.64±0.97, P=0.025) and ESR (28.10±6.64 vs. 23.09±7.65 mm/h, P=0.042) between healthy elderly and RA elderly patients. Elderly patients with RA were significantly more prone to have cognitive impairment (P=0.002), fall (P=0.005), malnutrition (P<0.001), urinary incontinence (P<0.001), and functional disability (P=0.021) compared to healthy elderlies and young RA patients. The results of binary logistic regression revealed that in elderly RA patients, higher DAS-28 score [odds ratio (OR) = 1.96; 95% CI 1.03, 3.84; P=0.041] was an independent risk factors for the GSs. The prevalence of some features of GSs were higher in the elderly RA patients than healthy elderly and young RA patients.

Efficacy of Tocilizumab Monotherapy Versus Tocilizumab and Methotrexate Combination Therapy in the Prevention of Radiographic Progression in Rheumatoid Arthritis: An Analysis Using Individual Patient Data From Multiple Clinical Trials

ObjectiveTo compare the effects of preventing radiographic progression (in its 3 components) of tocilizumab (TCZ) monotherapy with those of TCZ and methotrexate (MTX) in combination therapy (TCZ + MTX), and to evaluate possible effect modifiers in this model.MethodsRandomized trials that compared TCZ monotherapy to TCZ + MTX combination therapy for differences in radiographic progression were analyzed on an individual patient data level using mixed‐effects models, and data were collected from 820 subjects with either early rheumatoid arthritis (RA) or established RA. Outcomes were classified as the absence of radiographic progression after 2 years (i.e., preventing radiographic progression) as measured by total Sharp/van der Heijde score (SHS), erosion score, and joint space narrowing (JSN) score. Effect modification by baseline joint damage, disease duration, and Disease Activity Score in 28 joints (DAS28) was studied.ResultsOverall, TCZ + MTX combination therapy was more effective in preventing radiographic progression compared to TCZ monotherapy, which was measured by total SHS score. However, in patients with early RA who had more joint damage compared to those with less joint damage at baseline (relative risk [RR] 1.02 versus RR 0.91, respectively) or in patients with a lower DAS28 score compared to those with a higher DAS28 score (RR 1.04 versus RR 0.92, respectively) at baseline, this advantage disappeared. In patients with established RA, the advantage of TCZ + MTX versus TCZ alone in the prevention of radiographic progression disappeared with a longer disease duration at baseline (RR 1.04 versus 0.83). Results of erosion scores as an outcome were in line with these findings, though findings for JSN scores were less clear.ConclusionCombination therapy with TCZ + MTX is more effective in preventing radiographic progression compared to TCZ monotherapy, but the effectiveness of TCZ monotherapy may approximate the effectiveness of TCZ + MTX in patients with early RA who have more joint damage and/or a lower DAS28 at baseline and in patients with established RA who have longer disease duration.

Study of transforming growth factor beta 1 gene +869T/C polymorphism in Egyptian rheumatoid arthritis patients and its relation to disease activity

This study intended to explore the relationship between the +869T/C polymorphism of the transforming growth factor-β1 (TGF-β1) gene and rheumatoid arthritis (RA) predisposition and activity in Egyptian patients. The study involved 30 patients suffering from RA and 30 apparently healthy participants as the control group. The +869T/C polymorphism of the TGF-β1 gene was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) process. The TGF-β1 + 869 CT genotype and CT+TT genotypes in RA patients showed a significant increase than the control group (OR=3.782 and 3.824, CI=1.046-13.680 and 1.150-12.713, P=0.043 and 0.029, respectively). T allele showed a significant increase in patients than in controls (OR= 2.104, CI 1.015- 4.361, P = 0.046). The TGF-β1 +869 CT+TT genotypes were accompanied by higher DAS-28 scores which express higher disease activity, and increased levels of RF, Anti-CCP, ESR, and CRP. In conclusion, the TGF-β1 +869T/C gene polymorphism may be accompanied by an increased predisposition to RA and with its severity in Egyptian RA patients.

Morphological Parameters in Quadriceps Muscle Were Associated with Clinical Features and Muscle Strength of Women with Rheumatoid Arthritis: A Cross-Sectional Study.

Background: Rheumatoid arthritis (RA) is an autoimmune, inflammatory and chronic disease that may lead to loss of muscle mass, muscle strength and decreased functionality. Our objectives are to assess the quadriceps muscle morphology by ultrasound (MU) and verify its associations with clinical features, muscle strength and physical function in RA patients. Methods: In this cross-sectional study, RA women (≥18 years) were included. Morphological parameters in quadriceps muscle consisted of the muscle thickness and pennation angle of rectus femoris (RF), vastus intermedius (VI) and vastus lateralis (VL). RA activity was measured by a 28-joint disease activity score (DAS28), muscle strength by handgrip and chair stand tests, and physical function by health assessment questionnaire (HAQ), timed-up-and-go (TUG) test and short physical performance battery (SPPB). Results: Fifty-five patients were included (age: 56.73 ± 9.46 years; DAS28: 3.08 ± 1.29). Muscle thickness in RF, VI and VL were negatively associated with age (RF, p < 0.001; VI, p = 0.013; VL, p = 0.002) and disease duration (RF, p < 0.001; VI, p = 0.005; VL, p = 0.001), and were positively associated with handgrip strength (RF, p = 0.015; VI, p = 0.022; VL, p = 0.013). In addition, decreased muscle thickness in VI (p = 0.035) and a smaller pennation angle in RF (p = 0.030) were associated with higher DAS-28 scores. Conclusion: Quadriceps muscle morphology by ultrasound appears to be affected by age, disease duration, disease activity and muscle strength in patients with RA. MU can be a useful method to evaluate the impact of the disease on skeletal muscle.

Effects of MTHFR genetic polymorphism on inflammatory protein osteopontin in RA patients: A gender based study in North Indian population

BackgroundRheumatoid arthritis (RA) is a systemic chronic inflammatory disease that ultimately damages bone and cartilage of joints leading to disability. Genetic polymorphism in methylene tetrahydrofolate reductase (MTHFR) gene has been identified as potential marker of susceptibility or disease severity in RA. Risk of RA is three times higher in women than men. Several cytokines and proteins play significant role in synovitis of RA patients. Osteopontin (OPN) is the pro-inflammatory cytokine reported to be associated with synovitis in RA, as it generates T-helper-1 (TH1)-mediated cellular immune response. ObjectiveTo study the impact of MTHFR gene polymorphism on the serum levels of OPN in RA patients and to investigate the cause of greater disease severity in women than men. Patients and methodsThe study included sixty RA patients (eleven men and forty-nine women) from different regions of Uttar Pradesh, North India. OPN was estimated by using enzyme-linked immunosorbent assay and other serological parameters such as Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), C-reactive protein (CRP), triglycerides (TGA), cholesterol, uric acid, albumin and total protein were estimated using commercially available kits. MTHFR A1298C and C677T polymorphism was genotyped using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) based assays. Disease activity score and health questionnaire was assessed in all patients. ResultsMean age of patients was 44.53 ± 1.59 in women and 46.27 ± 4.22 in men with greater duration of morning stiffness in women than men. There were differences in TJC, SJC and DAS-28 score between men and women. OPN levels were found significantly higher in women than men. Other serological parameters were insignificantly higher in women than men. Genotypic study revealed that MTHFR genotypes are not associated with serum OPN levels. However, the disease activity scores (DAS-28), total joint count (TJC) and swollen joint count (SJC) were significantly associated with 1298CC genotype. Frequency distribution of MTHFR gene between men and women indicates that 1298CC genotype was more frequent in women than men and hence it might be one of the factors to cause disease severity more in women than men. ConclusionA1298C polymorphism is a predictor to the disease severity in RA patients. Patients with homozygous mutant CC genotype have a higher DAS-28 score along with TJC and SJC. The significantly higher OPN levels in female subjects suggest that disease severity is more in women than men. However, other parameters such as SGOT, SGPT, CRP, TGA, creatinine, uric acid, albumin and total protein were higher in women but the change was insignificant.

Ankle Joint in Active Rheumatoid Arthritis

Background: Ultrasonography (US) is a useful tool for imaging, which can be used for assessment of joints and per articular structures in all rheumatologic disorders. Ankle and foot sonography requires a linear high-frequency transducer; a 7.5 to 15 MHz probe is commonly used. The aim of this study was to evaluate ankle joint affection in active Rheumatoid arthritis and its value in assessment of disease activity by using US, and its correlation to disease duration, sex and age.Methods: A total of 63 patients with Rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria. 20 age and sex matched control volunteers were included. Evaluation of disease activirty by DAS-28. US examination of both ankles were done for patients and controls. High frequency US with 12 MHZ linear probe was used.Results: Our results show that ankle synovitis was found significantly higher among RA patients (18.3%) compared to controls (2.5%); p value = 0.013. although tenosynovitis and erosions were higher among cases (27% and 8.7%; respectively) than controls (15% and 0%; respectively); the differences were non-significant. We found that ankle affection as seen by US was significantly related to the activity of RA. Patients with higher DAS-28 score were more like to have ankle affection and also to have bilateral ankle affection; both with significant differences.Conclusion: It can be stated that ankle evaluation by US should be considered more in RA assessment, and further studies should be done to uncover the under-etsimation of ankle involvement in RA patients.

Detection of Some Genetic Polymorphism and Serological Factors Associated with Rheumatoid Arthritis in Egyptian Patients

Background: Rheumatoid arthritis is a chronic inflammatory autoimmune disease thatis characterized by destruction of cartilage and bone. PADI4 gene encoding the peptidyl arginine deiminase 4 citrullinating enzyme that has been found to be over expressed in rheumatoid arthritis patients. Objective: To investigate relation between PADI4 gene polymorphisms and anti–cyclic citrullinated peptide (Anti-CCP) autoantibody levels in sera of Egyptian rheumatoid arthritis patients, and to find its relevance to the disease activity(DAS28 score) and other inflammatory markers as Rheumatoid factor (RF). Methods: PADI4-89 andPADI4 -92 single nucleotide polymorphisms (SNPs) were analyzed in thirty RA patients and twenty healthy controls by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Serum anti-CCP levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: PADI4-89 genotype A/G was present in RA patients at higher frequency compared to controls (P = 0.024). (G) allele frequency was significantly higher in RA patients than in controls (P= 0.047). Level of Anti – CCP was significantly higher in RA patients serum than in controls (P= 0.000).PADI4-89 A/G + G/G genotype and PADI4-92 C/G+GG genotype were associated with higher DAS28 score, Rheumatoid factor (RF), and anti-cyclic citrullinated protein (Anti – CCP). Significant positive correlation was found between serum level of Anti– CCP and DAS28 score (P= 0.023). Conclusion: The SNPs A/G and G/G of PADI4-89 were associated with RA susceptibility. Relation was found between both PADI4 polymorphism and anti-CCP levels.

SERUM FETUIN-A LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is the second most common rheumatic disease. In recent decades, there has been an active search for and study of biologically active substances involved in the pathogenesis of RA, which can serve as a starting point in designing new drugs for targeted therapy of this disease. The hepatokine fetuin-A (FA) is one of these substances.Objective: to investigate serum FA levels in patients with RA.Subjects and methods. The investigation enrolled 110 patients with RA. All the patients underwent the following set of studies: general blood test and determination of the serum levels of C-reactive protein (CRP), serum FA, rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies, cartilage degradation products (CartiLaps), and urine creatinine. A control group consisted of 30 apparently healthy individuals whose serum FA level was determined in order to obtain reference values.Results and discussion. The normal FA level varied from 653.55 to 972.19 μg/ml. All the patients with RA were divided into two groups: 1) 23 patients with a low FA level (&lt;653.55 μg/ml) and 2) 87 patients with a normal FA levels (≥653.55 μg/ml). The groups differed significantly in anti-CCP antibody concentrations, disease activity, radiological stages, functional classes, and the presence of complications. Patients with lower FA levels were noted to have increased CRP concentrations, erythrocyte sedimentation rate, and CartiLaps/urine creatinine ratio. The mean FA concentration was considerably and significantly lower in patients with higher DAS28 scores. Conclusion. Our investigation has revealed that there is a relationship between the levels of FA and the individual clinical manifestations of RA. The lower FA level is associated with higher disease activity and the aggressive phenotype of RA (the presence of anti-CCP antibodies, radiological stages III and IV, extra-articular manifestations and complications).

IL-37 gene variant (rs3811047): A marker of disease activity in rheumatoid arthritis: A pilot study

Background: Rheumatoid arthritis (RA) is a joint destructive disorder with great morbidity. Unraveling genetic determinants causing the disease would pave the road towards early detection and precise medicine. Interleukin 37 (IL-37), a natural inhibitor of innate immunity, was shown to be a key modulator in RA. Plasma levels were deregulated and correlated with disease activity. Therefore, we hypothesized the IL-37 gene variants could influence the clinical characteristics of RA patients.Objective: This is a pilot study to assess the association of rs3811047 variant of IL-37 gene with RA development and disease activity in an Egyptian population.Methods: A total of 100 individuals (50 RA patients and 50 healthy individuals) were enrolled in the study. Disease activity score of 28 joints (DAS28) was estimated for RA patients. Genotyping was performed using Real-Time PCR technology.Results: There was no statistically significant association between genotype frequencies of rs3811047 and RA risk. However, there was a significant relationship between the studied single nucleotide polymorphism (SNP) and disease activity. Patients carrying the GG genotype had higher DAS28 score than patients with AA or AG genotypes (p = .041).Conclusion: IL-37 gene rs3811047 SNP was associated with more severe RA disease activity in the current population. Larger epidemiological study is warranted to validate our results.

The association of obesity with disease activity, functional ability and quality of life in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Study/Early Rheumatoid Arthritis Network UK prospective cohorts.

To examine associations between BMI and disease activity, functional ability and quality of life in RA. Data from two consecutive, similarly designed UK multicentre RA inception cohorts were used: the Early RA Study (ERAS) and the Early RA Network (ERAN). Recruitment figures/median follow-up for the ERAS and ERAN were 1465/10 years (maximum 25 years), and 1236/6 years (maximum 10 years), respectively. Standard demographic and clinical variables were recorded at baseline and annually. Multilevel piecewise longitudinal models with a change point at 2 years were used with the 28-joint DAS (DAS28), ESR, HAQ and 36-item Short Form Health Survey (SF-36) physical (PCS) and mental (MCS) components as dependent variables. BMI was examined in separate models as both continuous and categorical variables (based on World Health Organization definitions) and up to 5 years from disease onset. BMI data from 2386 newly diagnosed RA patients (11 348 measures) showed an increase in BMI of 0.27 U annually (95% CI 0.21, 0.33). Baseline obesity was associated with a significant reduction in the odds of achieving a low year 2 DAS28 [OR 0.52 (95% CI 0.41, 0.650)]. At year 2, HAQ and SF-36 PCS scores were significantly worse but not at year 5 in patients obese at baseline. Obesity at year 2 was associated with higher DAS28 scores at year 2, but not at year 5, and also associated with significantly higher HAQ and SF-36 PCS scores at years 2 and 5. Obesity prevalence is rising in early RA and associates with worse disease activity, function and health-related quality of life, with a significant negative impact on achieving a low DAS28. The data argue strongly for obesity management to become central to treatment strategies in RA.

The Relationship Between Focal and Generalized Bone Loss in Rheumatoid Arthritis.

To determine if there is an association between focal and systemic bone loss in patients with RA. Bone loss is a hallmark finding in rheumatoid arthritis (RA) and manifests as localized, periarticular and systemic bone loss. RA patients were selected from the Consortium of Rheumatology Researchers of North America (CORRONA) database. Multiple logistic regression models were constructed to assess the association between the presence or absence of erosions and T-scores at the lumbar spine (LS) and total hips and adjusted for age, gender, body mass index (BMI), medications and disease activity indices. Data on erosions and T-scores were available in 3,898 and 5,099 subjects, respectively. Patients with erosions had a significantly lower LS T-scores (-0.9) compared to RA patients without erosions (p=0.0002). Similarly, the mean total hip T-scores were significantly lower in patients with (-1.4) compared to subjects without erosions (-1.0) (p<0.01). The odds of having no erosion increased by 21% for each 1-unit increase in LS T-score and 46% for each 1 unit increase in hip Tscore. Patients with erosions were significantly younger (p<0.01) had a lower BMI (p<0.01) and higher DAS28 scores than those without erosions. More patients with erosions were on anti-TNF therapy, disease modifying drugs and osteoporosis medications than patients without erosions (p<0.01, 0.003 and 0.0003). RA patients with bone erosions have significantly lower T-scores at the LS and hips compared with RA patients without erosions. These data suggest a relationship between localized and generalized bone loss in RA.

Heightened autoantibody immune response to citrullinated calreticulin in bronchiectasis: Implications for rheumatoid arthritis

Calreticulin (CRT) and citrullinated (citCRT) are implicated in rheumatoid arthritis (RA) pathology. citCRT binds to RA shared epitopes (SE) on HLA-DR molecules with high affinity and triggers pro-inflammatory events in adjacent cells. The aim of the study was to detect the presence of citCRT prior to developing RA and evaluate if citCT is a target for autoantibodies in RA cohorts with and without lung disease. Antibodies were assessed by ELISA against native CRT, citCRT and general protein citrullination, in sera from 50 RA patients without lung disease, 122 bronchiectasis (BR) patients, 52 bronchiectasis patients with RA (BRRA), 87 asthma patients and 77 healthy controls (HC). Serum citCRT was detected by immunoblotting and mass spectrometry. Genomic DNA was genotyped for HLA-DRB1 alleles. Patients were assessed for DAS28, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies. Extracellular citCRT was detected in BR patients sera prior to them developing RA. A citCRT SE binding peptide GEWKPR261citQIDNPDYK was identified. Anti-CRT antibodies were observed in 18% of BR patients with or without RA. Anti-citCRT antibodies were observed in ∼35% of BR or RA patients, increasing to 58% in BRRA patients. In the RA alone patients 7/20 (35%) who were negative for RF and anti-CCP were anti-CRT antibody positive and had higher DAS28 scores than triple negative RA alone patients. Three of the four BR patients who developed RA over 18 months were anti-citCRT+ve SE+ve. The detection of citCRT in BR and development of anti-citCRT in BR patients suggests citCRT antigens are early targets of antigenicity in these patients, especially in SE+ve patients prior to the onset of RA.

Predict Triangular Fibrocartilage Complex (TFCC) Tear in Severe Rheumatoid Arthritis by PD Ultrasound

The Triangular Fibrocartilage Complex (TFCC) is the main biomechanical stabilizer of the distal radioulnar joint, TFCC tear frequent occurred in patients with wrist pain. This study aimed to predict tear of the triangular fibrocartilage complex using high-resolution ultrasound in severe rheumatoid arthritis. We evaluated severe rheumatoid arthritis who received biological therapy. Ultrasound and magnetic resonance imaging (MRI) were performed before and one year after biological therapy. Those with TFCC were recorded. Logistical regression was used to search for the possible factors to predict TFCC tear. 54 patients were enrolled. There were 42 females and 12 males. 21(38.9%) developed TFCC tear after follow up one years. The mean age were 55.14±9.54 at TFCC tear group, compared with 56.45±14.04(p=0.596). The body mass index were 22.81±2.59 kg/m2 at TFCC tear group, compared with 23.61±2.76 kg/m2 (p=0.136). The tear group had higher power Dopper ultrasound score at dorsal radio-carpal joint (1.90±1.30 vs 1.33±0.99, p=0.011), higher DAS28 score (6.36±0.47 vs 5.58±0.65, p=0.011) than non tear group. In logistical regression analysis, the higher pretreatment PD score had a significantly higher risk of TFCC tear (p=0.010, OR=1.987, 95% CI 1.180-3.344), while high DAS28 also had a significantly higher risk of TFCC tear (p=0.004, OR=5.924, 95% CI 1.781-19.706). These results show higher wrist PD score predict future TFCC tear in severe rheumatoid arthritis. So we recommended using PD score before biological therapy to early monitor of possible future TFCC tear.

Anti-CCP is Associated with Greater Disease Burden in Kashmiri Population with Rheumatoid Arthritis

Aim: To analyse the diagnostic value of anti-cyclic Citrullinated Peptide (anti-CCP) and to associate it with disease severity in patients with rheumatoid arthritis in Kashmiri population. Methods: The serum levels of anti-CCP levels were measured in 150 RA patients and 30 healthy controls by ELISA technique. Result: 118 (78.66%) patients were positive for anti-CCP while none of the healthy controls were positive for the test. The mean ± SD serum anti-CCP levels were significantly (p 20 mm/h (p = 0.01), RF positivity (p = 0.0001) and High DAS28 Score (p = 0.0001). Conclusion: Serum anti-CCP is a very accurate marker for RA diagnosis and the patients with higher levels of anti-CCP have more aggressive form of disease. Therefore, its early detection may help clinicians in early diagnosis and appropriate management of the disease.

TNF-Α, IL-1β and IL-6 Cytokine Gene Expression in Synovial Fluid of Rheumatoid Arthritis and Osteoarthritis Patients and Their Relationship with Gene Polymorphisms

Objective: To analyse and compare TNF-α, IL-1β and IL-6 mRNA expression of rheumatoid arthritis (RA) and osteoarthritis patients (OA) and to study the relationship between mRNA expression and promoter polymorphisms of these genes in RA patients. Method: A total of 20 RA, 10 OA and 10 healthy controls were taken in this study. The mRNA expression was quantified by qRT-PCR method and polymorphic analysis done by PCR-RFLP method. Result: TNF-α, IL-1β and IL-6 mRNA expression was significantly increased in the synovial fluid of both RA and OA patients as compared to healthy controls but with a higher fold change in RA than OA with TNF-α: 10.70 fold in RA vs 3.58 fold in OA; IL-1β: 5.61 fold in RA vs 2.42 fold in OA and IL-6: 2.58 fold in RA vs 1.70 fold in OA. The TNF-α and IL-1β mRNA expression was higher in RA patients with higher DAS28 Score (p = 0.02 and p = 0.009 respectively). TNF-α and IL-1β mRNA expression was significantly higher in the carriers of TNF-α -238 GG (p = 0.04) and IL-1β-511 TT (p = 0.03) genotypes respectively. Conclusion: We conclude that TNF-α, IL-1β and IL-6 cytokines play an important role in the pathogenesis and disease severity of RA. Also, the difference in cytokine gene expression between RA and OA is more quantitative than qualitative. Therefore, suggesting a more intense inflammatory nature of RA than OA. Moreover, the TNF- α-238 GG and IL-1β-511 TT genotypes are associated with higher mRNA expression, therefore are susceptibility markers to RA.

Increased disease activity, severity and autoantibody positivity in rheumatoid arthritis patients with co-existent bronchiectasis.

Patients with rheumatoid arthritis (RA) and co-existent bronchiectasis (BRRA) have a five-fold increased mortality compared to rheumatoid arthritis alone. Yet previous studies have found no difference in clinical and serological markers of RA disease severity between BRRA patients and RA alone. However, RA disease activity measures such as Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and anti-cyclic citrullinated peptide antibodies (anti-CCP) have not been studied, so we assessed these parameters in patients with BRRA and RA alone. BRRA patients (n=53) had high-resolution computed tomography proven bronchiectasis without any interstitial lung disease and ≥2 respiratory infections/year. RA alone patients (n=50) had no clinical or radiological evidence of lung disease. DAS28-CRP, rheumatoid factor (immunoglobulin M) and anti-CCP were measured in all patients, together with detailed clinical and radiology records. In BRRA, bronchiectasis predated RA in 58% of patients. BRRA patients had higher DAS28 scores (3.51 vs. 2.59), higher levels of anti-CCP (89% vs. 46%) and rheumatoid factor (79% vs. 52%) (P=0.003) compared to RA alone. Where hand and foot radiology findings were recorded, 29/37 BRRA (78%) and 13/30 (43%) RA alone had evidence of erosive change (P=0.003). There were no significant differences between groups in smoking history or disease-modifying anti-rheumatic drug/biologic therapy. Increased levels of RA disease activity, severity and RA autoantibodies are demonstrated in patients with RA and co-existent bronchiectasis compared to patients with RA alone, despite lower tobacco exposure. This study demonstrates that BRRA is a more severe systemic disease than RA alone.