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ID PMID Title PublicationDate abstract
34665703 Combined seronegativity in Sjögren's syndrome. 2021 Nov OBJECTIVES: To describe the clinical spectrum of Sjögren's syndrome (SS) patients with combined seronegativity. METHODS: From a multicentre study population of consecutive SS patients fulfilling the 2016 ACR-EULAR classification criteria, patients with triple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(+)] and quadruple seronegativity [anti-Ro/SSA(-), anti-La/SSB(-), RF(-) and ANA(-)] were identified retrospectively. Both groups were matched in an 1:1 ratio with 2 distinct control SS groups: i) classic anti-Ro/SSA seropositive patients [SS(+)] and ii) classic anti-Ro/SSA seropositive patients with negative rheumatoid factor [SS(+)/RF(-)] to explore their effect on disease expression. Clinical, laboratory and, histologic features were compared. A comparison between triple and quadruple seronegative SS patients was also performed. REESULTS: One hundred thirty-five SS patients (8.6%) were identified as triple seronegative patients and 72 (4.5%) as quadruple. Triple seronegative patients had lower frequency of peripheral nervous involvement (0% vs. 7.2% p=0.002) compared to SS(+) controls and lower frequency of interstitial renal disease and higher prevalence of dry mouth than SS(+)/RF(-) controls. Quadruple seronegative patients presented less frequently with persistent lymphadenopathy (1.5% vs. 16.9 p=0.004) and lymphoma (0% vs. 9.8% p=0.006) compared to SS(+) controls and with lower prevalence of persistent lymphadenopathy (1.5% vs. 15.3% p=0.008) and higher frequency of dry eyes (98.6% vs. 87.5% p=0.01) and autoimmune thyroiditis (44.1% vs. 17.1% p=0.02) compared to SS(+)/RF(-) SS controls. Study groups comparative analysis revealed that triple seronegative patients had higher frequency of persistent lymphadenopathy and lymphoma, higher focus score and later age of SS diagnosis compared to quadruple seronegative patients. CONCLUSIONS: Combined seronegativity accounts for almost 9% of total SS population and is associated with a milder clinical phenotype, partly attributed to the absence of rheumatoid factor.
35127719 Diverse Roles of F-BoxProtein3 in Regulation of Various Cellular Functions. 2021 Accumulated evidence shows that the F-box protein 3 (FBXO3) has multiple biological functions, including regulation of immune pathologies, neuropathic diseases and antiviral response. In this review article, we focus on the role of FBXO3 in inflammatory disorders and human malignancies. We also describe the substrates of FBXO3, which contribute to inflammatory disorders and cancers. We highlight that the high expression of FBXO3 is frequently observed in rheumatoid arthritis, leukemia, pituitary adenoma, and oral squamous cell carcinoma. Moreover, we discuss the regulation of FBXO3 by both carcinogens and cancer preventive agents. Our review provides a comprehensive understanding of the role of FBXO3 in various biological systems and elucidates how FBXO3 regulates substrate ubiquitination and degradation during various physiological and pathological processes. Therefore, FBXO3 can be a novel target in the treatment of human diseases including carcinomas.
34779998 Progress of Selenium Deficiency in the Pathogenesis of Arthropathies and Selenium Suppleme 2021 Nov 15 Selenium, an essential trace element for human health, exerts an indispensable effect in maintaining physiological homeostasis and functions in the body. Selenium deficiency is associated with arthropathies, such as Kashin-Beck disease, rheumatoid arthritis, osteoarthritis, and osteoporosis. Selenium deficiency mainly affects the normal physiological state of bone and cartilage through oxidative stress reaction and immune reaction. This review aims to explore the role of selenium deficiency and its mechanisms existed in the pathogenesis of arthropathies. Meanwhile, this review also summarized various experiments to highlight the crucial functions of selenium in maintaining the homeostasis of bone and cartilage.
34461260 Enhancing extracellular vesicles for therapeutic treatment of arthritic joints. 2021 Nov 1 Extracellular vesicles are small membrane-derived packages of information that are released from virtually all cell types. These nano-packages contain regulatory material including proteins, lipids, mRNA and microRNA and are a key mechanism of paracellular communication within a given microenvironment. Encompassed with a lipid bilayer, these organelles have been attributed numerous roles in regulating both physiological and pathological functions. Herein, we describe the role of EVs in the context of Rheumatoid and Osteoarthritis and explore how they could be harnessed to treat inflammatory and degenerative joint conditions. These structures offer a promising therapeutic strategy for treating musculoskeletal diseases due to their bioactive content, stability, small size and intrinsic ability to enter the avascular cartilage, a notoriously challenging tissue to target. We also discuss how EVs can be manipulated to load therapeutic cargo or present additional targeting moieties to enhance their beneficial actions and tissue regenerative properties.
34249008 Understanding Fatigue in Sjögren's Syndrome: Outcome Measures, Biomarkers and Possible In 2021 Sjögren's syndrome (SS) is an autoimmune disease affecting the salivary and lacrimal glands. Symptoms range from dryness to severe extra-glandular disease involving manifestations in the skin, lungs, nervous system, and kidney. Fatigue occurs in 70% of patients, characterizing primary SS (pSS) and significantly impacting the patient's quality of life. There are some generic and specific instruments used to measure fatigue in SS. The mechanisms involved with fatigue in SS are still poorly understood, but it appears fatigue signaling pathways are more associated with cell protection and defense than with pro-inflammatory pathways. There are no established pharmacological treatment options for fatigue in pSS. So far, exercise and neuromodulation techniques have shown positive effects on fatigue in pSS. This study briefly reviews fatigue in pSS, with special attention to outcome measures, biomarkers, and possible treatment options.
35340801 Evaluation of Ovarian Reserve in Women With Rheumatoid Arthritis. 2021 Dec Objective: Subfertility is commonly observed in patients with rheumatoid arthritis (RA). Although the causes are not well established, the alteration of the ovarian reserve is thought to contribute to the lower chances of pregnancy. This cross-sectional study aimed to evaluate the ovarian reserve in patients with RA. Materials and methods: Two parameters associated with ovarian reserves such as the antral follicle count (AFC) and the anti-müllerian hormone (AMH) were assessed in 38 patients with RA. We also analyzed the correlation of these parameters with the medication used to treat this pathology and with the illness severity. Results: The AMH levels in women with RA were comparable to those found on healthy individuals although the RA patients were more likely to have a low AFC. Ovarian reserve and RA were neither influenced by parameters of disease activity nor by the use of medication. Conclusion: The ovarian reserve in women with RA was similar to that found in healthy individuals.
34880942 Tocilizumab drug levels during pregnancy and lactation: A woman who discontinued tocilizum 2021 Dec The demand for tocilizumab is increasing in women who wish to bear children and who have active rheumatoid arthritis. Described here is a woman with rheumatoid arthritis who discontinued her tocilizumab therapy at the end of the first trimester and resumed it after delivery and where tocilizumab levels in maternal serum, infant serum, and the breast milk were measured. Tocilizumab was not detected in maternal serum just before delivery, or in umbilical cord blood or infant serum after birth. Tocilizumab levels in colostrum after intravenous injection were 0.57% of those in serum. Tocilizumab treatment in the first trimester was not associated with a significant drug level in the fetus at delivery and no fetal complications were noted .
34878205 The development and validation of a Patient-Perceived Methotrexate Intolerance Scale for u 2021 Dec 8 INTRODUCTION/OBJECTIVE: To develop a scale to measure methotrexate intolerance for use in adult rheumatoid arthritis (RA) patients and to describe its psychometric properties. METHODS: A three-phase study was conducted. During Phase 1, we conducted individual interviews with RA patients (n = 14) to inform our item development process. During Phase 2, we asked for RA patients' (n = 10) feedback on item readability, clarity and the scale's ability to measure methotrexate intolerance. During Phase 3, we had patients with RA (n = 204) complete the scale to develop a final version and to describe the scale's internal validity (Cronbach's alpha), test-retest reliability (intra-class correlation coefficients), construct validity and discriminant validity and the ability of the scale to discriminate between past and present methotrexate users. RESULTS: The newly developed, weighted scale (Patient-Perceived Methotrexate Intolerance Scale [PPMIS]) includes four subscales: Methotrexate Benefits, Methotrexate Risks-Side Effect Considerations, RA Risks and Methotrexate Risks-Willingness to Take Methotrexate Despite Risks. Cronbach's alpha ranged from 0.79 to 0.94. Test-retest reliability at 2 weeks was 0.73-0.88. Construct validity was supported with significant logical relationships between subscale scores and the existing methotrexate intolerance scale and past/present methotrexate use. The PPMIS was able to correctly classify RA patients as a past versus present methotrexate user 77% of the time. At the cut point of 3.29, the sensitivity of the PPMIS is 74% and specificity is 72% to correctly classify patients into past/present methotrexate use. CONCLUSION: This is the first known scale with favourable measurement properties to evaluate methotrexate intolerance using a patient-centred perspective.
34778324 Factors Determining Retreatment Time Interval of Rituximab in Korean Patients With Rheumat 2021 Unlike other biologic agents for rheumatoid arthritis (RA) that are administered at regular intervals even without flare, rituximab can be administered according to the timing of retreatment determined by the physician. Recently, there has been a tendency to prefer on-demand administration for disease flares rather than regular retreatment. We aimed to investigate the retreatment patterns of rituximab in patients with RA and to identify factors associated with extension of the time interval between retreatment courses. This study included RA patients on rituximab treatment who were enrolled in the Korean Rheumatology Biologics registry (KOBIO) or treated at Ajou University Hospital. Previous or current concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), corticosteroids, number of previous biologic agents, withdrawal, and time intervals of rituximab retreatment were collected. In case of treatment failure, the reasons such as lack of efficacy, adverse events, and others, were also identified. A total of 82 patients were enrolled. The mean follow-up period from the first cycle of rituximab was 46.1 months, and the mean interval between the retreatment courses was 16.3 months. The persistent rates of rituximab after 5 years was 72.4%. Concomitant use of at least two csDMARDs (β = 4.672; 95% CI: 0.089-9.255, p = 0.046) and concomitant use of corticosteroids (β = 7.602; 95% CI: 0.924-14.28, p = 0.026) were independent factors for extending the time interval between the retreatment courses. In conclusion, RA patients treated with rituximab in Korea show high persistence rates. Concomitant use of two or more csDMARDs and concomitant use of corticosteroids with rituximab are associating factors of extending the retreatment time interval. These findings should be considered when selecting rituximab as a treatment for patients with RA.
34760835 Emergent Vertebral Artery Embolization during C12 Screw Fixation for Rheumatoid Arthritis. 2021 Oct The subaxial screw fixation technique is commonly used for fixation in a wide range of cervical diseases, including traumatic, degenerative, and neoplastic diseases, rheumatoid arthritis (RA), and spondyloarthropathy. Although it is regarded as a relatively safe procedure, several complications may be encountered during surgery, such as vertebral artery (VA) and nerve root injuries, facet violation, and mass fracture. We report a case of endovascular embolization after VA injury during a high cervical spinal surgery. A 48-year-old woman was scheduled for C-1-2-3 posterior fixation. Plain radiography of the cervical spine revealed a severely unstable state. During dissection around the C1 lateral mass on the right side, sudden brisk arterial bleeding was observed. On vertebral angiography, flow voiding was noted above the right V3 portion. After checking patent collateral flow from the contralateral VA, routine coil embolization was performed to pack the V3 segment. Iatrogenic vascular injuries due to spinal surgery are rare but serious complications. For patients with RA, we recommend careful preoperative evaluation before a high cervical surgical procedure to avoid iatrogenic VA injury and endovascular interventions that are safe and effective in the diagnosis and treatment of such vascular injuries.
34209074 Anti-Inflammatory Effects of Low-Dose Glucocorticoids Compensate for Their Detrimental Eff 2021 Jun 30 OBJECTIVES: This study aimed to provide reliable information on the impact of low-dose glucocorticoids (GCs) on the bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: This retrospective study enrolled 933 patients with RA who continued the consumption of GCs (GC group) and 100 patients who had discontinued consumption for >1 year (no-GC group). The BMD values were measured at baseline and follow-up, and the annual rate of change in BMD between the groups was compared using dual-energy X-ray absorptiometry. We used multiple linear regression analysis to identify the factors associated with changes in BMD. RESULTS: The demographic characteristics and use of medical treatments affecting bone metabolism were similar between the two groups. Furthermore, there were no significant differences in the annual rate of changes in BMD and incidence of newly developed osteoporosis and incidental fractures between the two groups. Multiple linear regression analysis revealed that the disease activity score for 28 joints with erythrocyte sedimentation rate was the only factor affecting the annual rate of changes in BMD, and it was inversely proportional to changes in BMD. CONCLUSION: The benefits of GC therapy in attenuating inflammation compensate for the risk of osteoporosis if adequate measures to prevent bone loss are implemented in patients with RA.
34179140 Sex-Specific Association of Left Ventricular Hypertrophy With Rheumatoid Arthritis. 2021 Objectives: Clinical expression of rheumatoid arthritis (RA) varies by gender, but whether cardiovascular disease (CVD) is gender related in RA is unknown. Left ventricular (LV) hypertrophy (LVH) is a hallmark of CVD in RA patients. We investigated whether the association of LVH with RA is gender driven. Methods: Consecutive outpatients with established RA underwent echocardiography with measurement of LVH at baseline and one follow-up. All participants had no prior history of CVD or diabetes mellitus. We assessed CVD risk factors associated with LVH at follow-up, including sex, age, arterial blood pressure, and body mass index (BMI). We also evaluated inflammatory markers, autoimmunity, disease activity, and the use of RA medications as predictors of LVH. Results: We recruited 145 RA patients (121 females, 83%) and reassessed them after a median (interquartile range) of 36 months (24-50). At baseline, women were more dyslipidemic but otherwise had fewer CVD risk factors than men, including less prevalent smoking habit and hypertension, and smaller waist circumference. At follow-up, we detected LVH in 42/145 (44%) RA patients. LV mass significantly increased only in women. In multiple Cox regression analysis, women with RA had the strongest association with LVH, independently from the presence of CVD risk factors (OR, 6.56; 95% CI, 1.34-30.96) or RA-specific characteristics (OR, 5.14; 95% CI, 1.24-21.34). BMI was also significantly and independently associated with LVH. Conclusion: Among established RA patients, women carry the highest predisposition for LVH.
34041071 Evaluation of prescription practices in rheumatoid arthritis at the rheumatology clinic in 2021 Feb OBJECTIVE: This study was aimed to analyze the prescription pattern of disease modifying anti-rheumatic drug (DMARD) therapy in patients with rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. METHODOLOGY: This cross-sectional study was conducted in 150 RA patients who were given DMARD therapy. Patient's demographic details, drugs prescribed with their dosage and administration routes and the usage of complementary and alternative medicine (CAM) therapy were recorded to study the prescription pattern. RESULTS: Overall, 4 DMARDs were prescribed in all the studied patients: Methotrexate (n = 150), hydroxychloroquine (n = 35), leflunomide (n = 5), and adalimumab (n = 1). Single DMARD therapy with methotrexate was prescribed to 110 (73.3%) followed by double therapy with methotrexate + hydroxychloroquine in 35 (23.3%), triple therapy (methotrexate + hydroxychloroquine + leflunomide) in 4 (2.7%) and triple therapy with biological DMARD (methotrexate + hydroxychloroquine + leflunomide + adalimumab) in 1 (0.7%) patient. Adjuvant therapy drugs included: Prednisolone (n = 150), folic acid (n = 150), naproxen (n = 150), calcium (n = 150), vitamin D (n = 150) and indomethacin (n = 40). Of the total, 61.4% patients also took complimentary alternative medicine (CAM) therapy. CONCLUSION: Our study concludes that the most commonly prescribed DMARDs in our setting, to patients of RA, in descending order of frequency were methotrexate, followed by hydroxychloroquine, leflunomide and lastly adalimumab. A total of five adjuvant medications were commonly prescribed to all patients. There was a high prevalence of self-medicated CAM therapy in the majority of these patients.
33928006 Tocilizumab: Another medication related to osteonecrosis of the jaws? A case report and li 2021 Introduction: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication in patients receiving antiresorptive medication, such as bisphosphonates and denosumab, for different oncologic and non-oncologic diseases. Here, we report a case of MRONJ in a patient treated with tocilizumab, a humanized anti-interleukin-6 receptor antibody that effectively treats moderate to severe rheumatoid arthritis in adults. Case description: A 45-year-old female patient diagnosed with severe rheumatoid arthritis, who had been undergoing intravenous tocilizumab therapy for three years without history of bisphosphonate use, was referred to our department. Four weeks previously, several teeth in the maxilla and mandible were removed under local anesthesia by her dentist. Two weeks after the extractions, she felt pain in both jaws. We diagnosed wound dehiscence and delayed healing of the alveolar bone after the tooth extractions. Digital volume tomography showed persistent dry alveolar sockets. The patient underwent surgical debridement of necrotic bone, and intravenous antibiotics were administered in hospital. Five months later, wound dehiscence reoccurred in the same regions. Histopathological analysis of bone biopsies revealed a diagnosis of MRONJ. Four months later, wound dehiscence occurred in the left maxillary alveolar ridge, and local bone resection was performed under antibiotic treatment. Twenty-four months after the last surgery, wound dehiscence had healed completely without signs of recurrence. Discussion: Osteomyelitis of the jaw in patients treated with tocilizumab has not been reported often. This case confirms the potential role of this interleukin-6 receptor inhibitor in the pathogenesis of MRONJ and shows that patients who receive tocilizumab with MRONJ-like symptoms should be closely monitored. The pathomechanism of MRONJ under tocilizumab therapy remains unclear, so dental practitioners, maxillofacial surgeons, and rheumatologists should look for signs of MRONJ in patients receiving tocilizumab to prevent MRONJ onset.
33777988 Dietary Fibers (Gum Arabic) Supplementation Modulates Hepatic and Renal Profile Among Rheu 2021 Background: Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects the synovial joints with systemic manifestations. RA has a major impact on liver and kidney functions as part of the disease pathogenesis or as a sequel of disease medications or, mostly, both of them. The kidney and liver involvement increases the RA morbidity and mortality. Nowadays, dietary interventions are proposed as potential modifiers for disease severity. Gum Arabic (GA) is acacia senegal exudates; it is soluble fiber with prebiotic properties. GA has been discovered to be protective against experimental nephrotoxicity and hepatotoxicity, with comparable findings in human studies. This article addresses the effect of GA on hepatic and renal profile among RA patients. Methods: Forty patients aged 18-70 received GA daily for 12 weeks as a single dose of 30 g. The liver enzymes, total protein level, serum albumin, serum globulin level, urea, creatinine, and serum electrolytes have been measured as a baseline after 4 weeks and by the end of the study. Cobas C311 (Roche, Germany) automated chemistry analyzer directly determined the values for total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine. The study ethically has been approved by the Ethical Committee of the National Medicines and Poisons Board. Trial Registration Identifier: NCT02804581. Results: Regarding the liver enzymes, GA has significantly decreased the liver enzymes apart from alkaline phosphatase, which showed no significant change. In contrast, GA has increased the serum albumin level with a minor impact on the serum globulin level. Furthermore, GA has also significantly decreased the level of urea (P = 0.0001) and level of Sodium (P = 0.002) with nonsignificant change on creatinine and potassium concentrations. Conclusion: GA presents hepatic and renal protective effects among RA patients, evidenced by the significant reduction of urea and liver enzymes. Thus, it can be recommended as a dietary supplement for RA patients. Nonetheless, we recommend further investigation to support our findings.
33553167 Regulatory Role of the RNA N(6)-Methyladenosine Modification in Immunoregulatory Cells and 2020 Rheumatoid arthritis (RA) is a systemic autoimmune disease for which the etiology has not been fully elucidated. Previous studies have shown that the development of RA has genetic and epigenetic components. As one of the most highly abundant RNA modifications, the N(6)-methyladenosine (m(6)A) modification is necessary for the biogenesis and functioning of RNA, and modification aberrancies are associated with various diseases. However, the specific functions of m(6)A in the cellular processes of RA remain unclear. Recent studies have revealed the relationship between m(6)A modification and immune cells associated with RA. Therefore, in this review, we focused on discussing the functions of m(6)A modification in the regulation of immune cells and immune-related bone homeostasis associated with RA. In addition, to gain a better understanding of the progress in this field of study and provide the proper direction and suggestions for further study, clinical application studies of m(6)A modification were also summarized.
34117886 Current and emerging biological therapy in adult-onset Still's disease. 2021 Sep 1 Adult-onset Still's disease (AOSD) is a rare, but characteristic non-familial, multi-genic systemic auto-inflammatory disorder, characterized by high spiking fever, salmon-like evanescent skin rash, polyarthritis, sore throat, hyperferritinemia and leucocytosis. The hallmark of AOSD is a cytokine storm triggered by dysregulation of inflammation. Nowadays, with advances in anti-cytokine biologic agents, the treatment of AOSD is no longer limited to NSAIDs, glucocorticoids or conventional synthetic DMARDs. In this review, we focussed on the roles of these cytokines in the pathogenesis of AOSD and summarized the current and emerging biological therapy.
35069829 Silencing CoREST inhibits the viability and migration of fibroblast-like synoviocytes in T 2022 Feb Fibroblast-like synoviocytes (FLSs) have functions in the pathogenesis of rheumatoid arthritis (RA) through the onset of synovitis, the growth of pannus and the destruction of cartilage and bone. The significant increase in the proliferation, migration and invasion of FLSs induces the onset and advancement of RA. To date, the exact function of corepressor element-1 silencing transcription factor (CoREST) in RA remains unclear, but its expression has been determined in RA synovial tissues. In this study, the effects of CoREST were investigated in a TNF-α-induced FLS activation model. Following the silencing of CoREST expression with small interfering (si)RNA, the viability and migration of FLSs were evaluated. Furthermore, the possible molecular mechanisms were explored by detecting the expression of key factors, including matrix metalloproteinases (MMPs), lysine-specific histone demethylase 1 (LSD1) and associated cytokines, via reverse transcription-quantitative PCR and western blotting. CoREST expression increased not only in the RA synovial tissues, but also in the TNF-α-induced FLS activation model. Following the silencing of CoREST in the FLSs treated with TNF-α, cell viability was inhibited, and the migratory capacity of FLSs was suppressed, which was accompanied by the reduced expression of MMP-3 and MMP-9. The expression of LSD1 was also downregulated. There was a notable decrease in the synthesis of interferon-γ and interleukin (IL)-17, while IL-10 expression was increased. The knockdown of CoREST inhibited the viability and migration of FLSs stimulated with TNF-α. Thus, the suppression of CoREST may have crucial roles in the occurrence and development of RA.
34659493 The role of upadacitinib in the treatment of moderate-to-severe active rheumatoid arthriti 2021 Despite recent promising developments in the treatment of rheumatoid arthritis (RA), a substantial proportion of patients still cannot achieve the treatment targets: low disease activity and remission. Janus kinase (JAK) inhibitors have the potential to fill this important gap with their high efficiency, rapid onset of action, and acceptable safety profile. The fact that the previously approved two JAK inhibitors, tofacitinib and baricitinib, inhibit more than one JAK molecule raised the question whether a safer profile can be possible by inhibiting fewer JAK molecules. Upadacitinib, a JAK 1 selective molecule developed in this context has been evaluated in the SELECT phase-III study program and demonstrated a high and rapid efficacy in monotherapy as well as in combination with csDMARDs both in csDMARD-naive RA patients and in patients refractory to csDMARD and bDMARD treatments. Upadacitinib 15 mg once daily displayed a similar safety profile except for increased creatine phosphokinase (CPK) levels and herpes zoster (HZ) risk compared to its active comparators methotrexate (MTX) and adalimumab. Most of the CPK elevations were asymptomatic, and most of the HZ cases were not serious. Along with the randomized-controlled studies and meta-analysis results, upadacitinib 15 mg once daily has a favorable efficacy/safety profile. Long-term extensions of current studies and real-world data will be important to fully appreciate its potential in the treatment of RA.
34447918 B-cell Activating Factor Polymorphisms in Rheumatoid Arthritis-Associated Atherosclerosis. 2021 Jun Rheumatoid Arthritis (RA) is a common chronic inflammatory disorder affecting 0,5-1% of the population, characterised by intense cellular activation and inflammation in the affected joints ultimately leading to bone and cartilage destruction. Cardiovascular disease is the leading cause of death among patients suffering from RA, with chronic inflammation and genetic background emerging as major predisposing factors. Although the pathogenetic events leading to an increased rate of atherosclerosis in the affected group are not precisely described, several genetic variations have been suggested as possible mediators of this process. The aim of the current research proposal is to investigate the role of B-cell activating factor (BAFF) variants in the pathogenesis of RA-related atherosclerosis. Stored DNA samples from the Biobank in the Department of Physiology of the Medical School of the University of Athens from RA individuals and healthy controls will be analysed for polymorphisms of B-cell activating factor (BAFF) by polymeric chain reaction (PCR) based assays. Detection of plaque formation and calculation of the mean intima media thickness (mIMT) of the vessel wall will be performed in RA patients by using carotid and femoral artery ultrasonography. Complete personal and family history, biochemical and serological markers will be obtained from the RA group and associated with the genetic and IMT data. The results will be compared across the different subgroups in order to determine whether any particular genetic variants can act as prognostic markers for RA-related cardiovascular disease giving eventually new insights to atherosclerotic processes in the context of chronic inflammatory diseases. Such a result would invariably lead to a possible new treatment approach and/or prevention method to benefit this group of patients.