Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
33178540 Posterior Fossa Progressive Multifocal Leukoencephalopathy Secondary to Rituximab. 2020 Oct 10 Progressive multifocal leukoencephalopathy (PML) is a rare fatal central nervous system disorder characterized by infection-induced demyelination of white matter due to the opportunistic reactivation of John Cunningham virus in an immunocompromised patient. PML is associated with many immune-mediated diseases, lymphoproliferative conditions, and immunosuppressive agents. In this case report, we present a 79-year-old female patient diagnosed with rheumatoid arthritis who developed posterior fossa PML while on rituximab. She presented with subacute cerebellar ataxia, dysarthria, and nystagmus, and her brain MRI showed right pontine and pontocerebellar lesion with diffusion restriction and heterogenous enhancement highly characteristic of PML. Though many cases of PML with rituximab were reported in the literature, our case describes a rare type of PML affecting the posterior fossa in an HIV-negative patient on rituximab.
32535834 Rheumatoid Arthritis: The Impact of Mental Health on Disease: A Narrative Review. 2020 Sep Over 60% of rheumatoid arthritis (RA) patients achieve a good response after 12 months of treatment when following the European league against rheumatism (EULAR) guidelines for treatment. However, almost half of patients still suffer from moderate to severe disease activity despite this. In addition, mental health problems may remain despite reduced measures of inflammation systemically and within joints. Depression is two times more common in RA patients than in the general population, and intriguingly a bi-directional relationship with RA has been shown in cross-sectional studies. Chronic inflammation impairs the physiological responses to stress including effective coping behaviours, resulting in depression, which leads to a worse long-term outcome in RA. In RA patients, the pain score is not always solely related to inflammatory arthritis and immunological disease activity by Bąk et al. (Patient Prefer Adherence 13:223-231, [1]). Non-inflammatory pain secondary to anxiety, depression, sleep disturbance and the psychosocial situation needs to be considered whilst fibromyalgia, mechanical pain and neuropathic pain can also contribute to overall pain scores by Chancay et al. (Women's Midlife Health 5:3, [2]). Hence, the UK National Institute for Health and Care Excellence (NICE) guideline for the management of RA included psychological interventions for fatigue, low mood and social well-being (NICE NG100, 2018) [3], and the NICE clinical guidelines (CG91) [4] suggest managing mental health and depression in chronic medical conditions to improve treatment outcomes. This is a narrative review of the impact of mental health on RA disease activity in terms of patient-reported outcomes (PROs).
33213075 Missing Diagnosis, Pain, and Loss of Function in Older Adults with Rheumatoid Arthritis an 2020 Nov 17 Rheumatoid arthritis (RA) is characterised by a chronic, progressive inflammation in the joints and leads to substantial pain, disability, and other morbidities. Few studies document the occurrence of insufficiency fractures, but no studies document the patient's perspective on incurring an insufficiency fracture. The aim of this qualitative study was to explore the patients' perspective on how insufficiency fractures influence their level of activity and to detect their need for rehabilitation. Two focus-group interviews were performed with 10 patients diagnosed with RA and insufficiency fractures. The data from the focus-group interviews were subjected to thematic analysis to provide a sense of the important themes. The 10 patients were all females, aged 57-88 years. Magnetic resonance imaging were performed at a mean of six months and seven days. All patients identified the delayed diagnosis of fracture as a significant burden. They experienced pain but did not receive a diagnosis. When the patients were immobilised, some of them were offered aids such as crutches, which they were unable to use due to their RA. The patients needed a focus on diagnosis and individually customised rehabilitation, taking into account RA and including guidance concerning daily activities, aids, and the regain of physical function.
33072778 Prediction of Self-Perception of Patient in Rheumatoid Arthritis With the Key RNAs Express 2020 Self-perception in patients is their self-response to sensory stimuli. It is an important aspect of the existence and quality of life among patients. However, the inherent relationship between self-perception and the cellular activity at the molecular level is elusive. In this study, we aimed to explore the association of self-perception with RNA expression profile in patients with rheumatoid arthritis (RA) through computational analysis. We recruited 30 patients clinically diagnosed with RA and to age- and sex-matched controls without previous clinical history. In total, 5 self-perception measures and 30 RNA expression measures were derived from RA patients and control groups. A correlation analysis based on Spearman correlation and Logistic-regression methods was adopted to assess the correlation between self-perception and RNA expression. Quantitative analysis revealed that RA patients with poor self-perception were closely associated with RNAs expression, In addition, 3 key molecules including AC019117.2, LINC00638, and hsa_circ_0003972 could be used to predict self-perception changes in RA patients. Herein, our results will provide new insights in RA diagnosis however, the underlying mechanisms need to be further explored.
33042992 Delivery of Long Non-coding RNA NEAT1 by Peripheral Blood Monouclear Cells-Derived Exosome 2020 Emerging evidence has pointed out the importance of long non-coding RNAs (lncRNAs) in multiple diseases, the knowledge of rheumatoid arthritis (RA)-associated lncRNAs remains limited. In this present study, we aimed to elucidate the mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) from peripheral blood monouclear cell (PBMC)-derived exosomes (exos) on RA development by modulating the microRNA-23a (miR-23a)/murine double minute-2 (MDM2)/Sirtuin 6 (SIRT6) axis. RA was modeled in vivo by collagen induction in mice and in vitro by exposing fibroblast-like synoviocytes (FLSs) to lipopolysaccharide. Exos were isolated from human or mouse PBMCs, which were then were co-cultured with FLSs. Based on gain- and loss-of-function experiments, the cell proliferation and secretion of inflammatory factors were measured. LncRNA NEAT1 was found to be highly expressed in RA, and PBMCs-derived exos contributed to RA development by delivering lncRNA NEAT1. In lipopolysaccharide-induced FLSs, miR-23a inhibited the expression of MDM2, and overexpression of MDM2 partially rescued the inhibitory effect of miR-23a on FLS proliferation and inflammatory response. Mechanistically, MDM2 ubiquitination degraded SIRT6 in RA. LncRNA NEAT1 shuttled by PBMC-derived exos promoted FLS proliferation and inflammation through regulating the MDM2/SIRT6 axis. Furthermore, in vivo experiments suggested that downregulated lncRNA NEAT1 shuttled by PBMC-derived exos or upregulated miR-23a impeded RA deterioration in mice. This study highlights that lncRNA NEAT1 shuttled by PBMC-derived exos contributes to RA development with the involvement of the miR-23a/MDM2/SIRT6 axis.
32158341 A Review on Chronic Pain in Rheumatoid Arthritis: A Focus on Activation of NR2B Subunit of 2020 Feb Chronic pain is a debilitating condition that occurs after tissue damage, which substantially affects the patient's emotional state and physical activity. The chronic pain in rheumatoid arthritis (RA) is the result of various autoimmune-induced inflammatory reactions in the joints. Both types of peripheral and central pain processing can lead to sensitisation. Non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) can result in potent anti-inflammatory effect. However, these drugs are not able to suppress the pain from RA for a prolonged period. For years, researchers have examined the role of the N-methyl-D-aspartic acid receptor 2B (NR2B) subunit of N-methyl-D-aspartate receptors (NMDAR) in chronic and neuropathic pain models. This NMDAR subtype can be found in at the peripheral and central nervous system and it represents an effective therapy for RA pain management. This review focuses on the NR2B subunit of NMDAR and the different pathways leading to its activation. Furthermore, specific attention is given to the possible involvement of NR2B subunit in the peripheral and central pathogenesis of RA.
32596007 The association Between Occupational Exposure to silica and Risk of Developing Rheumatoid 2020 Jun BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease with systemic inflammatory arthritis. This meta-analysis was conducted to examine the association between occupational exposure to silica and the risk of developing RA among different workers. METHODS: In this meta-analysis, we searched relevant published studies using major electronic databases including Scopus, PubMed, ISI Web of Science, and Google Scholar search engine up to October 2019, and the references of retrieved articles were also checked for further possible sources. A random-effects model was used to account for heterogeneity among the results of the studies using the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The Q-statistic and I(2) tests were calculated to assess heterogeneity between the studies. RESULTS: The pooled calculation of OR indicated a significant association between occupational exposure to silica and risk of developing RA among different workers (OR = 2.59, 95% CI = 1.73 to 3.45). In addition, the pooled estimates of OR in smokers were statistically significant (OR = 2.49, 95% CI = 1.13 to 3.86). CONCLUSIONS: The findings of the present study reveal that occupational exposure to silica may be associated with increased risk of developing RA.
32104275 Anti-CCL22 increases regulatory T cells in CD4(+) T cells of rheumatoid arthritis patients 2020 Mar Abnormality in the number and function of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) in peripheral blood has been linked to the initiation and progression of rheumatoid arthritis (RA). Effect of chemokine CCL22 on the number of Tregs in CD4(+) T cells and the underlying mechanism were investigated. Downregulation of peripheral Tregs were observed while upregulation of serum chemokine CCL22 in RA patients. Tregs count and the expression of FOXP3 (Tregs function-related maker) and phosphorylated-signal transducer and activator of transcription 5 (p-STAT5) in CD4(+) T cells from RA patients were increased while C-C chemokine receptor 4 (CCR4) was decreased by anti-CCL22 antibody, however, recombinant CCL22 resulted in the opposite effects in CD4(+) T cells from the healthy control. STAT5 inhibitor significantly reversed the effects of anti-CCL22 antibody. Similarly, sinomenine, an anti-arthritis drug, which decreased CCL22 and CCR4, showed the same trends as the above events, and was reversed by recombinant CCL22 or STAT5 inhibitor. Collectively, anti-CCL22 induced the number of Tregs via STAT5 pathway, leading to expansion of Tregs and subsequently to control of the autoimmune reaction in RA patients. Our study provides s novel strategy for RA treatment.
34046564 Change of ARASHI scores for large joints in rheumatoid arthritis patients treated with aba 2021 Mar OBJECTIVES: This study aims to investigate large joint damage progression using the assessment of rheumatoid arthritis by scoring of large joint destruction and healing in radiographic imaging (ARASHI) score in patients with rheumatoid arthritis (RA) treated with abatacept for three years. PATIENTS AND METHODS: A total of 71 consecutive patients with RA (7 males, 64 females; median age 68 years; range, 41 to 81 years) and joint lesions (141 shoulders, 139 elbows, 141 hips, 134 knees, and 142 ankles) treated with abatacept for three years were examined. Radiographic changes were assessed using the ARASHI score, and factors associated with radiographic progressive damage of large joints were analyzed using multivariate logistic regression. RESULTS: The three-year radiographic progressive damage rates for the upper and lower limb large joints were 18.3% and 22.5%, respectively. Rates for the shoulder and knee decreased significantly (p=0.025 and 0.039, respectively), whereas rate for the ankle increased significantly (p=0.043). Multivariate logistic regression analysis identified the baseline ARASHI status score as an independent predictor of progressive damage of upper limb large joints within three years (p=0.004; odds ratio, 1.17). The cutoff value of the ARASHI status score for the upper limb large joints was 4, as determined from the receiver operating characteristics curve. No significant predictors of progressive damage were identified in the lower limb large joints within three years. CONCLUSION: The greatest suppression of the radiographic progressive damage of large joints was achieved for the shoulders and knees. Meanwhile, ankle damage progressed. Therefore, ankle joint damage should be monitored even in patients treated with abatacept. In the upper limbs, prescribing abatacept to patients with RA depending on their state of upper limb large joint damage may suppress damage progression.
32244809 Increased Sensitivity of PBMCs Isolated from Patients with Rheumatoid Arthritis to DNA Dam 2020 Apr 1 Rheumatoid arthritis (RA) is a systemic, inflammatory disease of the joints and surrounding tissues. RA manifests itself with severe joint pain, articular inflammation, and oxidative stress. RA is associated with certain types of cancer. We have assumed that RA patients' increased susceptibility to cancer may be linked with genomic instability induced by impaired DNA repair and sensitivity to DNA damaging agents. The aim of this work was to analyze the sensitivity of peripheral blood mononuclear cells (PBMCs) isolated from RA patients to DNA damaging agents: tert-butyl hydroperoxide (TBH), bleomycin, ultraviolet (UV) radiation, and methyl methanesulfonate (MMS) and calculate the repair efficiency. TBH induce oxidative DNA lesions repaired mainly by base excision repair (BER). Bleomycin induced mainly DNA double-strand breaks repaired by non-homologous end joining (NHEJ) and homologous recombination repair (HRR). We included 20 rheumatoid arthritis patients and 20 healthy controls and used an alkaline version of the comet assay with modification to measure sensitivity to DNA damaging agents and DNA repair efficiency. We found an increased number of DNA breaks and alkali-labile sites in the RA patients compared to those in the controls. Exposure to DNA damaging agents evoked the same increased damage in both groups, but we observed statistically higher PMBC sensitivity to TBH, MMS, bleomycin as well as UV. Examination of the repair kinetics of both groups revealed that the DNA lesions induced by TBH and bleomycin were more efficiently repaired in the controls than in the patients. These data suggest impaired DNA repair in RA patients, which may accelerate PBMC aging and/or lead to higher cancer incidence among RA patients.
32993091 Environment and Lifestyle: Their Influence on the Risk of RA. 2020 Sep 26 BACKGROUND: Rheumatoid arthritis (RA) is a complex disease in which environmental agents are thought to interact with genetic factors that lead to triggering of autoimmunity. METHODS: We reviewed environmental, hormonal, and dietary factors that have been suggested to be associated with the risk of RA. RESULTS: Smoking is the most robust factor associated with the risk of RA, with a clear gene-environment interaction. Among other inhalants, silica may increase the risk of RA in men. There is less evidence for pesticides, pollution, and other occupational inhalants. Regarding female hormonal exposures, there is some epidemiological evidence, although not consistent in the literature, to suggest a link between hormonal factors and the risk of RA. Regarding dietary factors, available evidence is conflicting. A high consumption of coffee seems to be associated with an increased risk of RA, whereas a moderate consumption of alcohol is inversely associated with the risk of RA, and there is less evidence regarding other food groups. Dietary pattern analyses (Mediterranean diet, the inflammatory potential of the diet, or diet quality) suggested a potential benefit of dietary modifications for individuals at high risk of RA. CONCLUSION: To date, smoking and silica exposure have been reproducibly demonstrated to trigger the emergence of RA. However, many other environmental factors have been studied, mostly with a case-control design. Results were conflicting and studies rarely considered potential gene-environment interactions. There is a need for large scale prospective studies and studies in predisposed individuals to better understand and prevent the disease and its course.
32676573 Treating to Target in Clinical Practice: The Results of a Questionnaire Completed by Greek 2020 Jun BACKGROUND: The Treat-To-Target (TTT) approach is an important part of clinical practice in rheumatology. Although this approach is well structured in rheumatoid arthritis (RA) and data are accumulating in psoriatic arthritis (PsA) and axial spondyloarthritides (AxSpA), the systematic application of this process in clinical practice can be further improved to achieve better treatment outcomes. OBJECTIVE: The aim of this study was to present the perspective of clinical rheumatologists on how they evaluate disease activity, in what patient groups they regularly use treatment targets, and how they prioritize treatment targets in spondyloarthritides. METHODS: A questionnaire consisting of eight questions on the management of RA, PsA and AxSpA (4 focusing on the use of indexes when setting treatment targets, 2 on the frequency and the patient groups to which these are being applied, and 2 on the physician's priorities in managing different manifestations of the SpA spectrum) was completed by private practice and hospital-based rheumatologists. RESULTS: 160 rheumatologists completed the questionnaire. The majority use the formal composite indexes in clinical practice, certain items from these indexes, and patients' evaluation of the treatment intervention. Indexes are applied frequently in most patient groups, and the priorities of rheumatologists include both musculoskeletal manifestations, as well as the other clinical aspects of the SpA spectrum. CONCLUSION: The results can contribute to the understanding of the adherence of rheumatologists to this TTT strategy.
32853994 Latent Factor Modeling of scRNA-Seq Data Uncovers Dysregulated Pathways in Autoimmune Dise 2020 Aug 12 Latent factor modeling applied to single-cell RNA sequencing (scRNA-seq) data is a useful approach to discover gene signatures. However, it is often unclear what methods are best suited for specific tasks and how latent factors should be interpreted. Here, we compare four state-of-the-art methods and propose an approach to assign derived latent factors to pathway activities and specific cell subsets. By applying this framework to scRNA-seq datasets from biopsies of patients with rheumatoid arthritis and systemic lupus erythematosus, we discover disease-relevant gene signatures in specific cellular subsets. In rheumatoid arthritis, we identify an inflammatory OSMR signaling signature active in a subset of synovial fibroblasts and an efferocytic signature in a subset of synovial monocytes. Overall, we provide insights into latent factors models for the analysis of scRNA-seq data, develop a framework to identify cell subtypes in a phenotype-driven way, and use it to identify novel pathways dysregulated in rheumatoid arthritis.
32477578 Testicular vasculitis: a diagnostic conundrum. 2020 Apr Vasculitis is rare in the context of testicular lesions but, when found, can be classified as a single organ vasculitis or part of a multi-organ inflammatory process. In the context of a patient with a pre-existing autoimmune disorder, this finding might cause diagnostic confusion and preferentially bias a physician towards attributing the condition to the known diagnosis or its treatment. This diagnostic bias can interfere with patient care and lead to over caution, resulting in a worse outcome for the patient involved. We describe such a patient with rheumatoid arthritis on biologic therapy.
32051038 Innate lymphoid cells in inflammatory arthritis. 2020 Feb 12 Aberrant activation and dysregulation of immune system is a common feature of many forms of inflammatory arthritis. Since their identification as a distinctive population of leukocytes, innate lymphoid cells (ILCs) have been considered crucial in maintaining tissue homeostasis and bridges between innate and adaptive immune system. Altered ILCs' subset distribution and function have been observed in a variety of autoimmune and chronic inflammatory diseases and suggest a subset-specific role of ILCs in the pathogenesis of immune-mediated inflammation. In this review, we focus on the current knowledge of ILC subset and their role in inflammatory arthritis, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), enteropathic arthritis, and other seronegative spondyloarthritis. By better understanding the biology and function of ILC subset in different disease settings, new therapeutic interventions can be anticipated by modulating dysregulated ILC responses toward promoting resolution of inflammation.
33375851 Current Management of Trigger Digit in Rheumatoid Arthritis Patients: A Survey of ASSH Mem 2020 Dec 29 BACKGROUND: Traditional dogma regarding management of rheumatoid arthritis (RA) patients with trigger digit symptoms holds that A1 pulley release should be avoided. Surgical release was thought to further destabilize the metacarpophalangeal joint. Biologic disease modifying anti-rheumatic drugs (DMARDs) have limited the development of hand deformities. Despite advances in RA treatment, many textbooks continue to discourage release of the A1 pulley in RA patients. The aim of this study was to determine if this belief is consistent with current trends in surgical management of trigger digits in patients with RA. METHODS: Active Members of the American Society for Surgery of the Hand (ASSH) were surveyed on their training and current practices as related to RA patients with trigger digits. RESULTS: Five hundred three surveys were completed (16% response rate). During training, 55% of ASSH Members were taught to avoid releasing the A1 pulley in RA patients. Seventy-one percent of respondents currently release the A1 pulley in RA patients with no preexisting deformities, no tenosynovial thickening, or if tenosynovectomy and flexor digitorum superficialis slip excision fail to relieve triggering. Forty percent reported that their practice has evolved toward more frequent release of the A1 pulley in RA patients. CONCLUSION: The majority of ASSH Active Members were taught during training to avoid surgical release of the A1 pulley in RA patients to prevent acceleration of finger deformities. Indications and contraindications for A1 pulley release are evolving along with the improved natural history of RA associated with the use of biologic DMARDs.
33374292 Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and C 2020 Dec 24 Fibroblasts, the most abundant cells in the connective tissue, are key modulators of the extracellular matrix (ECM) composition. These spindle-shaped cells are capable of synthesizing various extracellular matrix proteins and collagen. They also provide the structural framework (stroma) for tissues and play a pivotal role in the wound healing process. While they are maintainers of the ECM turnover and regulate several physiological processes, they can also undergo transformations responding to certain stimuli and display aggressive phenotypes that contribute to disease pathophysiology. In this review, we focus on the metabolic pathways of glucose and highlight metabolic reprogramming as a critical event that contributes to the transition of fibroblasts from quiescent to activated and aggressive cells. We also cover the emerging evidence that allows us to draw parallels between fibroblasts in autoimmune disorders and more specifically in rheumatoid arthritis and cancer. We link the metabolic changes of fibroblasts to the toxic environment created by the disease condition and discuss how targeting of metabolic reprogramming could be employed in the treatment of such diseases. Lastly, we discuss Systems Biology approaches, and more specifically, computational modeling, as a means to elucidate pathogenetic mechanisms and accelerate the identification of novel therapeutic targets.
33262784 Identification of Common Differentially Expressed Genes and Potential Therapeutic Targets 2020 Ulcerative colitis (UC) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases (IMIDs) with similar symptoms and common genomics. However, the relationship between UC and RA has not been investigated thoroughly. Therefore, this study aimed to establish the differentially expressed genes (DEGs) and potential therapeutic targets in UC and RA. Three microarray datasets (GSE38713, GSE1919, and GSE12251) were selected from the Gene Expression Omnibus (GEO) database for analysis. We used R software to identify the DEGs and performed enrichment analyses. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software were used to construct the protein-protein interaction (PPI) network and identify the hub genes. A regulatory network based on the constructed PPI was generated using StarBase and PROMO databases. We identified a total of 1542 and 261 DEGs in UC and RA. There were 169 common DEGs identified in both UC and RA, including 63 upregulated genes (DEGs1) and nine downregulated genes (DEGs2). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs1 and DEGs2 in the PPI network revealed that the genes enriched were involved in immunity. A total of 45 hub genes were selected based on high scores of correlation; three hub genes (SRGN, PLEK, and FCGR3B) were found to be upregulated in UC and RA, and downregulated in UC patients with response to infliximab treatment. The identification of novel DEGs and hub genes in the current study contributes to a novel perception for latent functional mechanisms and presents potential prognostic indicators and therapeutic targets in UC and RA.
33196006 Mental Health and Psychological Wellbeing in Rheumatoid Arthritis during COVID-19 - Can Ph 2020 Sep In response to the COVID-19 pandemic, many countries have adopted community containment to manage COVID-19. These measures to reduce human contact, such as social distancing, are deemed necessary to contain the spread of the virus and protect those at increased risk of developing complications following infection with COVID-19. People with rheumatoid arthritis (RA) are advised to adhere to even more stringent restrictions compared to the general population, and avoid any social contact with people outside their household. This social isolation combined with the anxiety and stress associated with the pandemic, is likely to particularly have an impact on mental health and psychological wellbeing in people with RA. Increasing physical activity and reducing sedentary behaviour can improve mental health and psychological wellbeing in RA. However, COVID-19 restrictions make it more difficult for people with RA to be physically active and facilitate a more sedentary lifestyle. Therefore, guidance is necessary for people with RA to adopt a healthy lifestyle within the constraints of COVID-19 restrictions to support their mental health and psychological wellbeing during and after the COVID-19 pandemic.
32967340 Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthr 2020 Sep 21 Paraoxonase 1 (PON1) is the high density lipoprotein-associated esterase which inhibits the development of atherosclerosis by metabolizing lipid peroxidation products as well as hydrolyzing proatherogenic metabolite of homocysteine (Hcy), Hcy thiolactone, which otherwise reacts with lysine groups of proteins, thus forming N-Hcy-protein in a process referred to as protein N-homocysteinylation. Rheumatoid arthritis (RA) is the chronic inflammatory autoimmune disease associated with increased risk of cardiovascular complications, but the underlying mechanisms are incompletely understood. We examined PON1 status and N-homocysteinylation of serum proteins in patients with RA. Blood was collected from 74 RA patients and 70 control subjects. PON1 activity was measured toward synthetic (paraoxon, phenyl acetate) and natural (Hcy thiolactone) substrates. PON1 protein concentration was measured by ELISA. Total Hcy as well as N-Hcy-protein were measured in serum as well. PON1 activity toward Hcy thiolactone was lower in RA patients than in control subjects which was accompanied by increased concentration of N-Hcy-protein despite normal total Hcy concentration. PON1 protein concentration was unchanged in the RA group, but the specific enzyme activity was reduced. When RA patients were categorized according to the DAS28-ESR score, PON1 concentration and enzymatic activity were lower whereas N-Hcy-protein was higher in those with high disease activity. PON1 activity and Hcy thiolactone were correlated with DAS28-ESR score and myeloperoxidase concentration. In conclusion, RA is associated with deficiency of PON1 activity and increased protein N-homocyseinylation which may contribute to accelerated development of cardiovascular diseases.