Clinical Manifestations Of Rheumatoid Arthritis Research Articles

Jinwu Jiangu capsule attenuates rheumatoid arthritis via the SLC7A11/GSH/GPX4 pathway in M1 macrophages

JinWu JianGu capsule (JWJGC) is a Chinese herbal medicine that alleviates the clinical manifestations of rheumatoid arthritis (RA). However, the mechanism of action requires further investigation.. This study aimed to investigate the anti-inflammatory effects of JWJGC on RA via the regulation of reactive oxygen species (ROS) and ferroptosis. JWJGC was administered to rats with collagen-induced arthritis (CIA) via oral gavage for 28 days. In vitro, M1 macrophages were pre-treated with JWJGC-containing serum. After assessing joint swelling and physiologic, the M1/M2 macrophage ratio was detected in CIA rats. The levels of ROS markers were assessed in the serum and cell supernatants. Liquid chromatography-tandem mass spectrometry analyses were employed to check lipid metabolism, and changes in mitochondrial morphology during ferroptosis were detected by transmission electron microscopy. Western blotting, immunofluorescence, immunohistochemistry, and qRT-PCR were performed to validate these results. JWJGC ameliorated CIA by reducing ROS levels in rats. It also restored the balance of the M1/M2 macrophage ratio and reduced the levels of macrophage-related inflammatory markers. Additionally, JWJGC affected lipid metabolism to alleviate inflammation by downregulating lipids associated with ferroptosis. It attenuated ferroptosis by modulating glutathione (GSH)/ Glutathione peroxidase 4(GPX4) expression in CIA rats. In vitro, JWJGC targeted M1 macrophages via the solute carrier family 7a member 11 (SLC7A11)/GSH/GPX4 signaling pathway. This study showed that JWJGC improved RA, primarily through the integrated regulation of the SLC7A11/GSH/GPX4 pathway in M1 macrophages. These findings provide an innovative therapeutic basis for RA treatment and expanding the clinical applications of JWJGC.

Adjunctive Therapies in Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune pathology that follows a chronic course characterized by the involvement of the synovial membrane of joints all over the body. Clinically, the disease is characterized by persistent and painful immune-mediated inflammation, which culminates in bone deformations and joint movement limitation. Alternative therapies, such as garlic, ginger, curcumin, and resveratrol, are beneficial given their anti-inflammatory properties. These alternative therapies are a secondary option for treating the clinical manifestations of rheumatoid arthritis, helping to improve the patient’s quality of life further and preventing future complications.

Gamma-delta T-cell large granular lymphocytic leukemia in the setting of rheumatologic diseases.

T-cell leukemia originating from large granular lymphocytes (T-LGL leukemia) is a rare lymphoid neoplasia characterized by clonal proliferation of large granular T lymphocytes expressing αβ or γδ T-cell receptor (TCR) on the cell membrane. γδT-LGL leukemia, accounting for approximately 17% of all T-LGL leukemia cases, is associated with autoimmune diseases. However, the features of γδT-LGL leukemia in patients with rheumatologic diseases are still insufficiently characterized. In this retrospective study, 15 patients with rheumatologic disease-associated γδT-LGL leukemia were included. The patients were obtained from a single center from 2008 to 2023. Data related to clinical characteristics and rheumatologic diagnoses were collected. Immunophenotype evaluations as well as T-lymphocyte clonality (based on TCR-γ, TCR-β, and TCR-δ gene rearrangements), and signal transducer and activator of transcription (STAT) three and STAT5B mutation analyses (by next-generation sequencing) were performed on blood, bone marrow, and spleen samples. All but one patient had rheumatoid arthritis (RA). In 36% of patients, manifestations of γδT-LGL leukemia were present before or concurrently with clinical manifestations of RA. Splenomegaly was observed in 60% of patients and neutropenia (<1.5 × 109/L) was detected in 93% of cases. CD4-/CD8- and CD4-/CD8+ subtypes were detected in seven cases each. Mutations in STAT3 were detected in 80% of patients; however, STAT5B mutations were not detected. Evaluations of T-cell clonality and variant allele frequencies at STAT3 in the blood, bone marrow, and spleen tissue revealed an unusual variant of CD4-/CD8- γδT-LGL leukemia with predominant involvement of the spleen, involvement of the bone marrow to a less extent, and no tumor cells in peripheral blood. The mechanism by which γδT-LGL leukemia may induce the development of RA in some patients requires further investigation. Cases of RA-associated γδT-LGL leukemia with neutropenia and splenomegaly but no detectable tumor-associated lymphocytes in peripheral blood (the so-called splenic variant of T-LGL leukemia) are difficult to diagnose and may be misdiagnosed as Felty syndrome or hepatosplenic T-cell lymphoma.

Role of Myostatin in Rheumatoid Arthritis: A Review of the Clinical Impact.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1β, transforming growth factor-beta (TGF-β), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-β superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research.

Level of glial cell derived neurotrophic factor in the blood plasma of rheumatoid arthritis patients and its relationship with alexithymia.

Glial cell derived neurotrophic factor (GDNF) has an important role in the pathogenetic mechanisms and clinical manifestations of rheumatoid arthritis (RA). Alexithymia is associated with a severe clinical course and worse prognosis, while the relationship between alexithymia and GDNF in RA patients has not been investigated before. The aims of the study were to investigate the GDNF level in blood plasma in RA patients depending on the presence of alexithymia and to evaluate the relationship of GDNF level with clinical manifestation and quality of life. Fifteen men and 73 women with RA were examined using the Disease Activity Score with 28-joint count (DAS28) with erythrocyte sedimentation rate (ESR) index, the Simple Disease Activity Index (SDAI), the Rheumatoid Arthritis Clinical Disease Activity Index (CDAI), the Visual Analogue Scale (according to the assessment of the patient - VAS-P and the assessment of the doctor - VAS-D), the Health Assessment Questionnaire (HAQ), the Toronto Alexithymia Scale (TAS-20), the Disability Rating Index (DRI) and SF-36 indexes. Glial cell derived neurotrophic factor level in the blood plasma was determined by enzyme-linked immunosorbent assay (ELISA). Forty percent of RA patients had alexithymia. Glial cell derived neurotrophic factor level in the examined patients was 3.73 ±2.59 pg/ml, in patients with alexithymia 4.08 ±2.87 pg/ml, without alexithymia 3.48 ±2.37 pg/ml (p = 0.295). Patients with alexithymia had a higher erythrocyte sedimentation rate (ESR) and index scores than patients without alexithymia - ESR: 34.29 ±14.22 vs. 22.73 ±12.03 mm/h (p = 0.017), DAS28: 6.53 ±0.66 vs. 6.09 ±0.55 (p = 0.017), VAS-D: 7.19 ±0.81 vs. 6.53 ±0.83 (p = 0.020), HAQ: 1.78 ±0.58 vs. 1.51 ±0.54 (p = 0.040). Also they had worse SF-36 indicators - physical functioning: 39.52 ±13.78 vs. 51.00 ±14.90 (p = 0.019), role functioning due to physical condition: 30.95 ±20.77 vs. 46.67 ±24.76 (p = 0.041), physical component of health: 31.47 ±11.44 vs. 41.61 ±15.88 (p = 0.028). In patients with alexithymia, a correlation was found between the GDNF level and severity of pain according to VAS-P: rS = 0.338, p = 0.044, and VAS-D: rS = 0.446, p = 0.006. Alexithymia was found in 40% of RA patients. Rheumatoid arthritis patients with alexithymia had a nonsignificantly higher GDNF level compared to patients without alexithymia. In RA patients with alexithymia, an association of GDNF level in the blood plasma with RA activity, loss of functional capacity and reduced quality of life was established. Alexithymia in RA patients is an important factor in the clinical manifestation of RA and modification of the pathophysiological role of GDNF.

Emerging Role of Interleukin-38 (IL-38) in the Development of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an incurable autoimmune disease. The role of interleukin-38 (IL-38), an anti-inflammatory cytokine, in RA is not fully understood, and its clinical relevance in RA remains unclear. This study aims to investigate the correlation of IL-38 with disease activity and the clinical manifestation of RA. In this cross-sectional study, patients with treatment-naïve RA (n = 63) and healthy controls (HC) (n = 60) were consecutively enrolled over a 15-month period. Patients with RA were categorized into three subgroups-low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)-using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Circulating levels of IL-38, tumour necrosis factor (TNF), IL-6, IL-17, IL-1β, and 25(OH)D were assessed using enzyme-linked immunosorbent assay (ELISA). Clinical data, including duration, tender joints count (TJC), swollen joints count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), bone mineral density (BMD), clinical disease activity index (CDAI), simplified disease activity index (SDAI), DAS28-CRP, joint musculoskeletal ultrasound (MSUS), and serological indicators were recorded. We determined the correlation between IL-38 and disease activity, as well as clinical manifestation in RA. At the macroscopic level, musculoskeletal ultrasonography of joints in different stages of disease activity in RA suggests that, as the disease progresses, arthritis in the hand becomes more severe, accompanied by synovial thickening and pronounced blood flow signals in the joint area. The expression of IL-38, TNF, IL-6, IL-17 and IL-1β significantly increased in patients with RA compared to HC. Noteworthy differences were observed in the blood flow signal score, synovial signal score, IL-38, TNF, IL-6, IL-17 and IL-1β among the three subgroups (LDA, MDA and HDA). As disease activity increased in patients with RA, the blood flow signal score, synovial signal score and expression of TNF, IL-6, IL-17 and IL-1β exhibited a gradual increase, while the expression of IL-38 showed the opposite pattern. Inverse correlations were identified between IL-38 and pro-inflammatory cytokines (IL-6, IL-17), as well as key clinical parameters, including disease duration, SJC, TJC and DAS28-CRP score. IL-38, intricately linked to the pathogenesis of RA, emerges as a promising therapeutic target for the management of this debilitating disease.

Comprehensive Review Of Rheumatoid Arthritis: Insights, Challenges, And Prospects

This comprehensive review explores the multifaceted landscape of rheumatoid arthritis (RA), encompassing its epidemiology, pathophysiology, clinical manifestations, diagnosis, treatment approaches, and the impact on patients' quality of life. The review delves into the global prevalence of RA, demographic patterns, and associated risk factors, shedding light on the complex interplay of genetics, immunology, and environmental triggers in disease development. The pathophysiological mechanisms involving immunological dysregulation, genetic factors, and environmental triggers are elucidated, providing a foundation for understanding the intricate processes driving RA. Detailed insights into the clinical manifestations of RA, including joint involvement, extra-articular manifestations, and the progression of the disease, are provided. The diagnostic landscape is explored, covering the ACR/EULAR classification criteria, diagnostic imaging, and laboratory tests that facilitate accurate and timely identification of RA. Treatment approaches, from pharmacological therapies like DMARDs and biologics to non-pharmacological interventions such as physical and occupational therapy, emphasizing a holistic management strategy. The economic burden of RA, its impact on healthcare utilization, and the broader societal implications are scrutinized, providing valuable insights into the challenges faced by both individuals and healthcare systems. Prevention and disease management strategies are highlighted, emphasizing the importance of early intervention, patient education, and public health initiatives in mitigating the impact of RA. Current challenges in RA management are outlined, with proposed future research directions aimed at advancing understanding and treatment.

Antifibrotic Agents in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular clinical manifestation of rheumatoid arthritis (RA) that has negative impacts on morbidity and mortality. In addition, there has been no proven treatment for RA-ILD to date. Thus, we planned a meta-analysis of a literature search to confirm the clinical effects of antifibrotic agents in RA-ILD patients. We conducted the literature search in Ovid MEDLIVE® databases, Cochrane Library databases, EMBASE, and KoreaMed and identified references elucidating the role of nintedanib or pirfenidone in adult patients with RA-ILD. Among the identified studies, those with comparative interventions, complete results of clinical trials, and available full text were included in the analysis. The primary outcome was the effect of the antifibrotic agent on disease progression in RA-ILD patients assessed with a mean difference in the change of forced vital capacity (FVC) and the proportion of patients with an increase in percent predicted FVC of 10% or more over 52 weeks. Analysis for heterogeneity was assessed through I2 statistics. Meta-analysis with a fixed effect model was performed on changes in FVC. A total of 153 articles were identified through database searches, of which 28 were excluded because of duplication. After additional screening, 109 studies were selected with full text and two articles qualified for analysis according to the set inclusion and exclusion criteria. As a result, two randomized controlled studies were selected, comparing nintedanib and pirfenidone to placebo, respectively. The meta-analysis revealed that antifibrotic agents showed a significant reduction in FVC decline compared to placebo in patients with RA-ILD (mean difference, 88.30; 95% CI, 37.10-139.50). Additionally, there were significantly fewer patients experienced an increase in percent predicted FVC of 10% or more in the antifibrotic agent group compared to the placebo group (Odds ratio 0.42; 95% CI 0.19-0.95, p = 0.04). There was no significant heterogeneity between the two included studies (χ2 = 0.35, p = 0.0007, I2 = 0%). The meta-analysis suggests that nintedanib and pirfenidone may have clinical utility in reducing disease progression in patients with RA-ILD. Further research is needed to confirm the clinical benefits of antifibrotic agents in RA-ILD.

Symposium 7

Pre-clinical rheumatoid arthritis (RA) is a phase of the disease that occurs before the characteristic symptoms and clinical manifestations of RA become evident. One key aspect of pre-clinical RA research has been the identification of biomarkers that can predict the development of RA in individuals who are at risk. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are often detectable in the pre-clinical phase, sometimes years before clinical onset. These biomarkers, along with genetic and environmental factors contribute to the risk profile for RA development. Synovial biopsy, serum and peripheral blood cell characterization, magnetic resonance imaging (MRI) and ultrasound, have allowed researchers to capture subclinical joint inflammation in individuals who do not yet exhibit clinical symptoms. This has provided valuable insights into the progression of RA, as well as the potential for early intervention to prevent irreversible joint damage. Understanding the pathogenesis of pre-clinical RA has revealed the role of several initial pathways that are relevant for the onset of the disease, paving the way for new treatment intervention and new very early diagnostic strategies. Ongoing research will continue to refine our understanding of this phase of the disease and optimize strategies for its management.

Features of clinical manifestations of rheumatoid arthritis in patients after failure of conventional synthetic disease-modifying antirheumatic drugs therapy depending on the signs of central sensitization

Central sensitization (CS) is a condition characterised by (associated with) neuroplastic changes in nociceptive neurons, sub-threshold afferent input, pain hypersensitivity and development widespread pain. Insufficient response to disease-modifying antirheumatic drugs (DMARDs) can be caused by CS.Objective – to evaluate the features of clinical manifestations of RA in patients with ineffective antirheumatic therapy, depending on the presence of signs of CS.Material and methods. The study group included 509 patients diagnosed with RA (according to ACR/EULAR classification criteria, 2010) with moderate or high disease activity (DAS28-CRP≥3.2) and ineffectiveness or intolerance of conventional synthetic DMARDs, biological DMARDs and JAK inhibitors. Disease activity in patient with RA was assessed by DAS28-CRP. Our study did not include an examination by a neurologist to detect signs of CS, so the Central Sensitization Inventory (CSI) (part one) was used. The BPI questionnaire was used for assessing clinical pain intensity. The PainDETECT, FSS, FIRST, HAQ questionnaires were used for screening neuropathic pain symptoms (NPS), fatigue, fibromyalgia signs and functional impairment, respectively. The HADS questionnaire was recommended for early diagnosis anxiety and depression disorders.Results. Signs of CS (CSI≥40), with a median of 42 [32; 53], were found in 57.2% of the examined patient. Patients with signs of CS were established to have poorer health measure (PGA – 64.6±13.5 and 53.5±16.8; p=0.001), higher pain intensity in all BPI scales, longer morning stiffness – 90 [30; 180] and 60 [20; 120] minutes (p=0.001), more painful joints – 8 [5; 12] and 7 [4; 10] (p=0.005), worse functional status in HAQ (1.65±0.7 and 1.08±0.5; p=0.001) and higher disease activity in DAS28-CRP (4.9±1.0 and 4.6±0.9; p=0.001) compared to patients without signs of CS. There was also direct correlation between CS and a high frequency of having an NPS (PainDETECT&gt;18) – 34.5% and 10.3% (p=0.001), significant anxiety and depression (HADS&gt;11) – 29,0% and 5.1% (p=0.001) and 26.3% and 4.2% (p=0.001) respectively, fatigue (FSS) – 96.5% and 70.4% (p=0.001), signs of fibromyalgia (FIRST≥5) – 38.4% and 6.1% (p=0.001).Conclusion. The presence of signs of CS in patient with RA significantly enhance many symptoms of disease, being associated with higher pain intensity, fatigue, impaired function, higher incidence of NPS, depression and anxiety, and fibromyalgia.

Serum Levels of IFABP2 and Differences in Lactobacillus and Porphyromonas gingivalis Abundance on Gut Microbiota Are Associated with Poor Therapeutic Response in Rheumatoid Arthritis: A Pilot Study.

Intestinal dysbiosis is related to the physiopathology and clinical manifestation of rheumatoid arthritis (RA) and the response to pharmacologic treatment. The objectives of this study were (1) to analyze the effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the abundance of gut microbiota's bacteria; (2) to evaluate the relationship between the differences in microbial abundance with the serum levels of intestinal fatty-acid binding protein 2 (IFABP2), cytokines, and the response phenotype to csDMARDs therapy in RA. A cross-sectional study was conducted on 23 women diagnosed with RA. The abundance of bacteria in gut microbiota was determined with qPCR. The ELISA technique determined serum levels of IFABP2, TNF-α, IL-10, and IL-17A. We found that the accumulated dose of methotrexate or prednisone is negatively associated with the abundance of Lactobacillus but positively associated with the abundance of Bacteroides fragilis. The Lactobacillus/Porphyromonas gingivalis ratio was associated with the Disease Activity Score-28 for RA with Erythrocyte Sedimentation Rate (DAS28-ESR) (r = 0.778, p = 0.030) and with the levels of IL-17A (r = 0.785, p = 0.027) in the group treated with csDMARD. Moreover, a relation between the serum levels of IFABP2 and TNF-α (r = 0.593, p = 0.035) was observed in the group treated with csDMARD. The serum levels of IFABP2 were higher in patients with secondary non-response to csDMARDs therapy. In conclusion, our results suggest that the ratios of gut microbiota's bacteria and intestinal permeability seems to establish the preamble for therapeutic secondary non-response in RA.

Chinese registry of rheumatoid arthritis (CREDIT) V: sex impacts rheumatoid arthritis in Chinese patients.

The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients. Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits. A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0 vs . 6.7 mg/L), pain visual analogue scale (4.8 vs . 4.5), patient's and physician's global assessment (4.9 vs . 4.5 and 4.9 vs . 4.5), 28-joint disease activity score using DAS28-CRP (4.3 vs . 4.0) simplified disease activity index (21.9 vs . 19.9), and clinical disease activity index (19.3 vs . 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4% vs . 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women. In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.

Interleukin-6 inhibitors: from the therapy of immuno-inflammatory rheumatic diseases to use in COVID-19

The key role in the development of chronic autoimmune inflammation is played by pro-inflammatory cytokines, in particular, interleukin 6 (IL-6). The introduction into clinical practice of monoclonal antibodies inhibiting IL-6 is a significant event in rheumatology and is currently considered as a promising direction in the treatment of immuno-inflammatory rheumatic diseases. The first inhibitor of IL-6 (IL-6), which entered the practice of rheumatologists, was tocilizumab (TCZ), the second – sarilumab (SAR). Numerous studies have shown the high effectiveness of iIL-6: the use of drugs leads to a rapid decrease in the clinical manifestations of rheumatoid arthritis (RA) and a decrease in laboratory signs of inflammation, contributing to the achievement of low activity or remission, improves the quality of life of patients, and also slows down the X-ray progression of the disease. At the same time, iIL-6 has a satisfactory safety profile. The universal problem of our time – the pandemic of a new coronavirus infection – has led to attempts to use IL-6 in patients with severe and critical disease, since IL-6 plays an important role in the pathogenesis of COVID-19, which is confirmed by the results of numerous studies. However, data on the efficacy and safety of these drugs in COVID-19 are contradictory, which requires conducting larger-scale controlled studies. This review examines the issues of the effectiveness and safety of TCZ and SAR in rheumatological patients and in patients with COVID-19. The review is illustrated with examples from real clinical practice.

Rheumatoid arthritis and DVT risk.

Studies show that patients with rheumatoid arthritis (RA) have an increased risk for deep vein thrombosis (DVT) compared with the general population. This article discusses the pathophysiology and clinical manifestations of RA, explores the DVT risk in patients with RA, and outlines critical nursing actions to care for these patients.

Comparison of clinical manifestations of rheumatoid arthritis in patients with moderate or high disease activity depending on the presence or absence of symptoms of neuropathic pain

Objective: to study the effect of neuropathic pain symptoms (SNP) on the clinical manifestations of rheumatoid arthritis (RA) in patients with moderate or high disease activity.Patients and methods.The 1st (main) group included 58 RA patients (84.5% of women, age 53.0±11.9 years), in whom SNP were identified using the DN4 (≥4) and PainDETECT (≥13) questionnaires. The 2nd (control) group included 43 patients with RA (79.1% women, age 48.8±14.4 years) who did not have SNP (DN4 ≤4 and PainDETECT ≤13). All patients received disease-modifying antirheumatic drugs (mainly methotrexate and leflunomide), 20% – biologic disease-modifying antirheumatic drugs. We compared groups 1 and 2 for RA activity (DAS28, CDAI, SDAI), pain intensity on a visual analogue scale (VAS, 0–100 mm), functional impairment (HAQ), patient global assessment (PGA, VAS), number of painful and swollen joints, quality of life (EQ-5D), signs of anxiety and depression (HADS), CRP level.Results and discussion. The RA activity in patients of the 1st and 2nd groups did not differ statistically significantly. Patients of the 1st group showed significantly higher indicators of the severity of pain, PGA and anxiety than patients of the control group: 71.0±12.5 and 54.7±17.5 mm, respectively (p&lt;0.001); 61.0±13.1 and 53.7±15.3 mm (p=0.045); 62.1 and 28.6% (HADS ≥7; p&lt;0.001), respectively.Conclusion.SNP are associated with higher rates of pain intensity, PGA, and anxiety in RA patients with moderate to high disease activity.

Osteoporosis risk factors analysis in rheumatoid arthritis patients: data from real practice

Background. Osteoporosis (OP) and its consequences is a pivotal medical and social problem. Rheumatic diseases especially rheumatoid arthritis (RA) is considered a key factor in the development of secondary OP. At the same time, patients with RA also have traditional risk factors (RF) for OP, as well as the adverse effects of drugs on bone metabolism. Consideration of the full spectrum in each patient with RA plays an important role in the individualized assessment of the risk of OP and the rational management.The aim. To analyze the most significant RF of OP in a cohort of patients with verified RA observed by primary care specialists.Materials and methods. Medical cards of 100 patients with determined RA (ACR / EULAR criteria) who were observed at out-patient clinics were studied. Along with the analysis of the clinical manifestations of RA, the registration of OP RF, both traditional and disease-related, was carried out with an analysis of the prevalence of RF in the investigated cohort.Results. The RA cohort under study was dominated by patients with erosive arthritis, disease duration of more than 5 years, RF and/or ACCP positivity, moderate activity, functional class 2–3. Based on the available instrumental data, systemic OP was diagnosed in 33% of patients, while DXA-densitometry was performed only in 5% of patients with osteoporotic fractures. Among the traditional RF, the most significant were female sex, age higher than 50 years, BMI less than 20 kg/m2 . The frequency of registration of these RF was significantly higher in the subgroup of patients with confirmed OP. Of the disease-associated RF, the most common were the following: duration of RA more than 5 years, activity of 2–3 degrees, high titer of RF and ACCP, X-ray stage II and higher, long term systemic GC use.Conclusions. In real practice, the diagnosis of OP in primary care in patients with RA is based on the available instrumental methods, preferably on standard radiography of bones and joints, which leads to underestimation and/or late diagnosis of OP. Patients with RA have a wide range of traditional and specific OP RFs, the assessment of which is important for determining the risk of fractures and timely prevention of OP complications.

Novel Nano Carriers for the Treatment of Progressive Auto Immune Disease Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is the most commonly occurring, progressive, autoimmune disease, affecting 1% of the population and the ratio of affected women is three times as compared to men in most developing countries. Clinical manifestations of RA are the presence of anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) in blood, tendered joints and soreness of the muscles. Some other factors which may lead to chronic inflammation are genetic and environmental factors as well as adaptive immune response. Several conventional drugs are available for the treatment of RA but have their own drawbacks which can be overcome by the use of novel drug delivery systems. The objective of the present review is to focus on the molecular pathogenesis of the disease and its current conventional treatment with special reference to the role of novel drug delivery systems encapsulating anti-rheumatic drugs and herbal drugs in passive and receptor-mediated active targeting against RA. On reviewing the conventional and current therapeutics against RA, we conclude that although the current therapy for the treatment of RA is capable enough, yet more advances in the field of targeted drug delivery will sanguinely result in effective and appropriate treatment of this autoimmune disease.

PADI2 Polymorphisms Are Significantly Associated With Rheumatoid Arthritis, Autoantibodies Serologic Status and Joint Damage in Women from Southern Mexico.

The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (β= -3.26; p = 0.03 and β = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (β= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.

Influence of Seasonal Vitamin D Changes on Clinical Manifestations of Rheumatoid Arthritis and Systemic Sclerosis.

Vitamin D [1,25(OH)2D—calcitriol] is basically a steroid hormone with pleiotropic biologic effects, and its impact on the regulation of immune system may influence several clinical conditions. Calcidiol (25OHD), as precursor of calcitriol, derives, for the most part (80%), from cutaneous cholesterol (7-dehydrocholesterol) under the action of UV-B (sunlight). Consequently, serum concentrations fluctuate during the year following the circannual rhythm of sun exposition. We will update about the available evidence regarding the complex influence of seasonal vitamin D changes on two different chronic connective tissue diseases, namely rheumatoid arthritis (RA) and systemic sclerosis (SSc). Notably, RA is an emblematic model of autoimmune disease with prevalent joint inflammatory features, while SSc is mainly an autoimmune progressive pro-fibrotic disease. However, in both conditions, low serum concentrations of 25OHD are involved in the pathogenesis of the diseases, and emerging data report their impact on clinical manifestations.

POS0381 PATIENTS AT RISK FOR RA SHOW THE SAME AMOUNT OF ACUTE SOLUBLE CARTILAGE DEGRADATION MARKERS AFTER PHYSICAL ACTIVITY COMPARED TO PATIENTS WITH ESTABLISHED RA

Background:Serum concentration of cartilage oligomeric matrix protein (COMP) is related to the degree of cartilage destruction in patients with rheumatoid arthritis (RA) and shows a mechanosensitive response to ambulatory loads. We showed previously, that individuals with positive for anti-citrullinated protein antibody (ACPA+) status already show bone loss. It is unclear if these individuals experience cartilage deterioration and how this is related to physical activity.Objectives:To test whether soluble COMP levels in ACPA+ display the same response as RA patients after a walking exercise and explore the association between overall serum COMP levels and physical activity.Methods:RA patients and ACPA+ individuals (IRACE cohort: Individuals at Risk for Arthritis Cohort Erlangen; Ethics approval 334_16B) were enrolled in the study after written informed consent. Inclusion criteria were age between 18 and 69 years, RA (by 2010 ACR/EULAR criteria) or ACPA+ (without clinical manifestation of RA and prior treatment with glucocorticoids, DMARDs and biologics). The study comprised three visits (baseline (Visit 1), 6 (Visit 2), and 12 months (Visit 3). During each visit, serum samples were collected after 30 minutes rest (pre) and at 0, 30, 60, and 120 minutes after a 30-minute walking exercise. Serum COMP concentration was analyzed by commercial ELISA. Physical activity duration (hours) was measured using an activity monitor for 7 consecutive days, and physical activity level (metabolic equivalent of the task (MET)) was quantified using the International Physical Activity Questionnaire (IPAQ). The reponse of COMP levels to the walking exercise was modelled using linear mixed-effects regression models. The association between physical activity and overall serum COMP concentrations was analyzed using a mixed-effects regression model (Random effects: individuals, visits and COMP measurement time points).Results:28 RA and 22 ACPA+ patients participated in this prospective study. Table 1 summarizes patient demographics and outcome measures. Serum COMP levels increased in response to the walking exercise in both groups but the acute response was not different in RA patients compared to ACPA+ individuals. Higher physical activity level by IPAQ was associated with higher overall COMP concentration. Doubling of total physical activity is associated with an increase in serum concentration of 0.32 U/L (95%CI 0.09 to 0.54, p=0.006). ACPA+ individuals but not RA patients show an association between serum COMP concentration and physical activity duration (Figure 1).Table 1.Summary of subject characteristics and outcome measures.DescriptivesMeasureACPA+RAindividuals, number (%)22 (44.0)28 (56.0)Age, years (mean (SD))47.6 (12.8)57.0 (9.1)Female, number (%)14 (28.0)19 (38.0)BMI, kg/m2, mean (SD)25.1 (5.6)27.2 (5.8)Anti-CCP positive (N)1714DAS28-score, mean (SD)2.5 (1.2)2.7 (1.4)Cartilage Oligomeric Matrix Protein (U/l)Visit 1Visit 2Visit 3ACPA+RAACPA+RAACPA+RApre-walking exercise9.4 (2.8)9.7 (3.8)10.8 (2.2)11.3 (4.5)10.2 (2.5)10.5 (3.9)09.5 (2.6)10.4 (3.9)11.8 (1.8)12.2 (4.0)10.1 (2.0)11.1 (4.6)309.2 (2.2)9.9 (3.6)10.8 (1.9)11.4 (4.4)9.2 (2.2)10.6 (4.2)609.2 (2.0)9.4 (4.0)10.4 (2.1)10.9 (4.5)8.6 (2.9)10.0 (4.0)1209.2 (2.1)9.5 (4.0)9.6 (1.8)10.9 (4.4)8.0 (2.4)9.9 (3.9)Figure 1.Estimated marginal mean COMP by physical activity duration for RA and ACPA+.Conclusion:Pre-exercise serum COMP concentration is similar in ACPA+ and RA and shows a similar increase in response to walking in both groups. Physical activity duration appears to influence serum COMP concentration in ACPA+. Given that acute COMP release was not different between ACPA+ and RA while overall COMP values are associated with physical activity level, the discrepancy between ACPA+ and RA for this association can be explained by reduced vigor or qualitative differences in physical activity.Disclosure of Interests:Lisa Bleckwedel-Rolack: None declared, Koray Tascilar: None declared, Veronika Nees: None declared, Julia Hühne: None declared, Axel Hueber: None declared, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Georg Schett Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Arnd Kleyer Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Anna-Maria Liphardt Speakers bureau: Mylan, Paid instructor for: Abbvie, Consultant of: MEDA Pharma, Grant/research support from: Novartis