Browse

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

ID PMID Title PublicationDate abstract
24813051 Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and 2014 Sep Interleukin (IL)-17 plays a critical role in inflammation. Most studies to date have elucidated the inflammatory role of IL-17A, often referred to as IL-17. IL-17F is a member of the IL-17 family bearing 50% homology to IL-17A and can also be present as heterodimer IL-17AF. This study elucidates the distribution and contribution of IL-17A, F and AF in inflammatory arthritis. Neutralizing antibody to IL-17A alone or IL-17F alone or in combination was utilized in the mouse collagen-induced arthritis (CIA) model to elucidate the contribution of each subtype in mediating inflammation. IL-17A, F and AF were all increased during inflammatory arthritis. Neutralization of IL-17A reduced the severity of arthritis, neutralization of IL-17A+IL-17F had the same effect as neutralizing IL-17A, while neutralization of IL-17F had no effect. Moreover, significantly higher levels of IL-17A and IL-17F were detected in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA). IL-17A and AF were detected in synovial fluid mononuclear cells (SFMC) in RA and OA, with IL-17A being significantly higher in RA patients. Enriched CD3(+) T cells from RA PBMCs produced singnificantly high levels of IL-17A and IL-17AF in comparison to OA peripheral blood CD3(+) T cells. IL-17A, F and AF were undetectable in T cells from SFMCs from RA and OA. While IL-17A, F, and AF were all induced during CIA, IL-17A played a dominant role. Furthermore, production of IL-17A, and not IL-17F or IL-17AF, was elevated in PBMCs, SFMCs and enriched peripheral blood CD3(+) T in RA.
23327689 Gingival crevicular fluid, serum levels of receptor activator of nuclear factor-κB ligand 2013 Nov BACKGROUND: This study is performed to evaluate gingival crevicular fluid (GCF) and serum levels of soluble receptor activator of nuclear factor-κB ligand (sRANKL), interleukin (IL)-17A, IL-17E, IL-17F, IL-17A/F, and osteoprotegerin (OPG) in women with rheumatoid arthritis (RA), osteoporosis (OPR), and those who are systemically healthy (SH), all with periodontal disease. METHODS: GCF and serum samples were obtained before any periodontal intervention from 17 women with RA, 19 with OPR, and 13 who were SH with periodontitis. Full-mouth clinical periodontal measurements were recorded. sRANKL, OPG, and IL-17 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Clinical periodontal measurements were similar in the three study groups. Although the total amounts of GCF albumin, OPG, IL-17A, and IL-17A/F were similar in the study groups, there were statistically significant differences in GCF concentrations of sRANKL, OPG, IL-17A, IL-17E, IL-17F, and IL-17A/F. The sRANKL/OPG ratios were significantly higher in the RA group than in the OPR and SH groups (P <0.05). Serum sRANKL, sRANKL/OPG, and IL-17A/IL-17E ratios were significantly higher, whereas OPG concentrations were significantly lower in the RA group compared to other groups (P <0.05). Serum IL-17A concentrations were significantly higher in the RA and OPR groups than in the SH group (P <0.05). CONCLUSION: Increased inflammatory mediator levels in patients with RA, despite the long-term use of various anti-inflammatory drugs, suggest that these patients may have a propensity to overproduce these inflammatory mediators.
24671499 No overall increased risk of cancer in patients with rheumatoid arthritis: a nationwide dy 2014 Oct The association between rheumatoid arthritis (RA) and cancer is still controversial. This study aimed to estimate cancer incidence (both overall and site-specific) among patients with RA and to determine whether their cancer risk was higher than in the general population. We used the nationwide dynamic cohort from the National Health Insurance Research Database of Taiwan and obtained a total of 30,504 patients with no history of cancer who were newly diagnosed with RA between 1996 and 2008; they were followed up until 2010. Standardized incidence ratios (SIR) by age for various types of cancer were calculated in 5-year calendar periods by 5-year age intervals (quinquinquennium) to compare elevated risk of increasing age and increased cancer rate in later calendar years in Taiwan. During 225,432 person-years of follow-up, 1,595 cancers occurred, corresponding to 7.08 per 1,000 person-years. The SIR for all cancers was 0.93 (95 % CI 0.88-0.97). Most cancers were found in the first 2 years after diagnosis of RA, but the incidence decreased afterward. A significant excess of Hodgkin's lymphoma (SIR 3.31, 95 % CI 1.24-8.81) and non-Hodgkin's lymphoma (SIR 3.18, 95 % CI 2.64-3.83) was seen among patients with RA, whereas the risk of colorectal cancer was 29 % lower than the general population. In conclusion, this study showed that patients with RA do not have increased overall risk of cancers but have higher risk of hematologic malignancies and lower risk of colorectal cancer, than the general population.
23253919 Next stage of RA treatment: is TNF inhibitor-free remission a possible treatment goal? 2013 Apr Biological agents targeting tumour necrosis factor (TNF) have revolutionised the treatment of rheumatoid arthritis (RA) and clinical remission has become a realistic treatment goal. Discontinuing anti-TNF therapy after sustained remission has emerged as an important area of investigation in rheumatology from the risk-benefit point of view, including health economic considerations. However, there is little information as to whether 'biologic-free remission' is possible after sustained remission following intensive treatment with TNF inhibitors in RA. European studies such as BeSt and OPTIMA in patients with early RA and Japanese studies such as remission induction by remicade in patients with RA and HONOR in patients with long-standing RA encountered during routine clinical practice have shown that, after a reduction in disease activity to clinical remission or low disease activity by infliximab or adalimumab in combination with methotrexate, patients can successfully remain in clinical remission without TNF inhibitors with no radiological and functional damage progression of articular destruction. Experimental findings in TNF-deficient mouse models suggest that TNF inhibitors may change the disease process of RA and bring about the potential of immunological remission, raising the possibility of a 'treatment holiday' of TNF inhibitors after intensive treatment.
24635802 Fibrosing cholestatic hepatitis after methotrexate and prednisone therapy for rheumatoid a 2014 Mar OBJECTIVES: Fibrosing cholestatic hepatitis is an aggressive and usually fatal form of viral hepatitis in immunosuppressed patients. We assessed the hepatotoxicity of methotrexate and prednisolone combination therapy in the background of hepatitis B virus infection. MATERIALS AND METHODS: We report the clinical course of a 55-year-old woman who underwent a deceased-donor liver transplant for fulminant liver failure. RESULTS: The patient's medical history was significant for hepatitis B virus infection and rheumatoid arthritis. Methotrexate and prednisolone combination therapy were started 5 months earlier. The patient was hospitalized because of an elevation in her liver enzymes and total bilirubin. Deterioration of liver functions and encephalopathy were developed 5 weeks after hospital admission. A deceased-donor liver transplant was performed, and pathological examination of recipient liver revealed fibrosing cholestatic hepatitis. The patient was reoperated on for bile leak and discharged 40 days after the deceased-donor liver transplant. CONCLUSIONS: The natural course of the current case was similar to previously reported cases with fibrosing cholestatic hepatitis. Clinicians should consider the potential hepatotoxicity of methotrexate and steroid therapy in hepatitis B virus infected patients.
24091294 Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of col 2014 Feb Current therapies for autoimmune chronic inflammatory diseases e.g. rheumatoid arthritis (RA) include inhibitors of inflammatory cytokines. However, these therapies can result in increased risk of infections. There is a need to explore alternate strategies that can control inflammation without compromising the innate ability to resolve infections. In this study, we examined the effect of small peptides derived from endogenous cathelicidin peptides in a murine model of collagen-induced arthritis (CIA). Cathelicidins are immunomodulatory peptides known to control infections. We demonstrate that the administration of the peptide IG-19, which represents an internal segment of the human cathelicidin LL-37, decreased disease severity and significantly reduced the serum levels of antibodies against collagen type II in the CIA model. IG-19 peptide reduced cellular infiltration in joints, prevented cartilage degradation and suppressed pro-inflammatory cytokines in the CIA mice. We also showed that not all cathelicidin-derived peptides exhibit similar functions. A bovine cathelicidin-derived peptide IDR-1018 did not exhibit the beneficial effects observed with the human cathelicidin LL-37-derived peptide IG-19, in the same murine model of CIA. This is the first study to provide evidence demonstrating the ability of a peptide derived from the human cathelicidin LL-37 to alleviate the arthritic disease process in a murine model of RA. Our results has lead us to propose a new approach for controlling autoimmune chronic inflammatory disorders such as RA, by using specific synthetic derivatives of endogenous host defence peptides. Cathelicidin-derived peptides are particularly attractive for their dual antimicrobial and anti-inflammatory actions.
24461738 [New therapies for rheumatoid arthritis]. 2014 Nov 18 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage and bone. Advances in the knowledge of disease pathogenesis allowed the identification of novel therapeutic targets such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6 or the system JAK/STAT phosphorylation. At present there are 5 TNF antagonists approved for RA. Tocilizumab blocks the pathway of IL-6 and is the only biological with proven efficacy in monotherapy. Rituximab modulates B cell response in RA. Abatacept provided new data on T cell involvement in the pathogenesis of RA. Tofacitinib is the first kinase inhibitor approved for this disease. Biologic drugs have proven efficacy, almost always in combination with methotrexate, and even halt radiographic progression. Monitoring infection is the main precaution in handling these patients.
23624939 Development and validation of a new radiographic scoring system to evaluate bone and carti 2013 Nov OBJECTIVE: To assess the reliability and sensitivity of a novel scoring method to evaluate the radiographic appearance of and longitudinal changes including joint remodeling in large joints with early and established rheumatoid arthritis (RA). METHODS: The ARASHI study group devised new radiographic scoring systems (Status score; range 0-16 points, and Change score; range -11 to 12 points) for evaluation of large joints with RA. Radiographs showing anterior/posterior views of large joints (shoulder, elbow, hip, knee, and ankle joints) taken at two time points (mean interval 2.3 years) were collected from 25 patients with established RA (5 patients for each of the 5 joints, 50 films in total), and an additional 5 films of each joint with severe joint destruction were collected from 5 different sets of RA patients. After consensus on the definition of each component and reader training, images were evaluated using the Larsen's grading system and the ARASHI Status and Change score by 9 independent senior orthopedic surgeons. The reliability was estimated by intra-class correlation coefficients (ICCs) and measurement error by 95% confidence intervals of minimum detectable change (MDC95). RESULTS: ARASHI Status score and Change score significantly correlated with Larsen's grade (r = 0.89, P < 0.0001) and follow-up-baseline differences in Larsen's grade (r = 0.83, P < 0.0001), respectively. Inter-reader ICCs were very high for both Status score (0.88, 95% confidence interval [CI], 0.83-0.92, P < 0.001) and Change score (0.92, 95% CI, 0.87-0.96, P < 0.001). Intra-reader ICCs were also very high for both Status score (0.92, 95% CI, 0.71-0.98, P < 0.001) and Change score (0.97, 95% CI, 0.91-0.99, P < 0.001). The MDC95 for inter-reader agreement were 4.18 (25% of maximum obtainable score, MOS) and 4.99 (21% of MOS) for Status score and Change score, respectively. The MDC95 for intra-reader agreement was acceptable with 2.82 (17% of MOS) and 3.02 (13% of MOS) for Status score and Change score, respectively. CONCLUSION: The ARASHI scoring method showed good inter-/intra-reader reliability with high ICCs and acceptable MDC95 with respect to each large joint and the components of both Status and Change scores. The results suggest that the ARASHI scoring method might be useful for the assessment of status, as well as longitudinal monitoring of destruction and remodeling of large joints with RA.
23434511 Disease-association analysis of an inflammation-related feedback loop. 2013 Mar 28 The IL-6-triggered positive feedback loop for NFκB signaling (or the IL-6 amplifier/Inflammation amplifier) was originally discovered as a synergistic-activation signal that follows IL-17/IL-6 stimulation in nonimmune cells. Subsequent results from animal models have shown that the amplifier is activated by stimulation of NFκB and STAT3 and induces chemokines and inflammation via an NFκB loop. However, its role in human diseases is unclear. Here, we combined two genome-wide mouse screens with SNP-based disease association studies, revealing 1,700 genes related to the IL-6 amplifier, 202 of which showed 492 indications of association with ailments beyond autoimmune diseases. We followed up on ErbB1 from our list. Blocking ErbB1 signaling suppressed the IL-6 amplifier, whereas the expression of epiregulin, an ErbB1 ligand, was higher in patients with inflammatory diseases. These results indicate that the IL-6 amplifier is indeed associated with human diseases and disorders and that the identified genes may make for potential therapeutic targets.
23266136 Custom intramedullary intercalating device for treatment of supracondylar fracture between 2014 Mar Management of periprosthetic fractures between ipsilateral total knee arthroplasty (TKA) and total hip arthroplasty (THA) is difficult, and is further complicated in the setting of poor femoral bone stock. We present a case of supracondylar fracture between THA and long-stemmed TKA femoral components in a patient with rheumatoid arthritis, deficient metaphyseal bone stock, and recurrent fractures. A long custom intramedullary intercalating component was devised to link the well-fixed existing THA stem to a revision distal femoral component. The resulting construct was stable and allowed for full weight-bearing ambulation, representing a useful treatment option in the management of periprosthetic fractures between revision TKA and well-fixed THA.
21240669 Cardiovascular risk in rheumatoid arthritis and systemic autoimmune rheumatic disorders: a 2013 Feb The pathogenesis of accelerated cardiovascular damage commonly characterizing patients affected by systemic chronic inflammatory and autoimmune rheumatic disorders is quite complex and still not fully clarified. However, it is well accepted that a strong relationship between multiple factors, including both traditional cardiovascular risk factors and disease-related inflammatory and autoimmune mechanisms, may in part explain the precocious atherosclerotic vessel damage and the increased incidence of cardiovascular events. Nevertheless, although several recent studies focused their attention on the investigation of these complex mechanisms, data regarding possible preventive strategies aimed to reduce long-term cardiovascular risk in these subjects are still lacking and not conclusive. In this setting, the early introduction of evidence-based preventive measures for the correct management of patients with systemic autoimmune disorders would be of extreme importance to reduce subclinical atherosclerosis incidence and possible major cardiovascular events.
25304517 Factors influencing rheumatologists' prescription of biological treatment in rheumatoid ar 2014 Oct 11 BACKGROUND: The introduction of biological drugs involved a fundamental change in the treatment of rheumatoid arthritis (RA). The extent to which biological drugs are prescribed to RA patients in different regions in Sweden varies greatly. Previous research has indicated that differences in health care practice at the regional level might obscure differences at the individual level. The objective of this study is to explore what influences individual rheumatologists' decisions when prescribing biological drugs. METHOD: Semi-structured interviews, utilizing closed- and open-ended questions, were conducted with senior rheumatologists, selected through a mix of random and purposive sampling. The interview questions consisted of two parts, with a "parallel mixed method" approach. In the first and main part, open-ended exploratory questions were posed about factors influencing prescription. In the second part, the rheumatologists were asked to rate predefined factors that might influence their prescription decisions. The Consolidated Framework for Implementation Research (CFIR) was used as a conceptual framework for data collection and analysis. RESULTS: Twenty-six rheumatologists were interviewed. A constellation of various factors and their interaction influenced rheumatologists' prescribing decisions, including the individual rheumatologist's experiences and perceptions of the evidence, the structure of the department including responsibility for costs, peer pressure, political and administrative influences, and participation in clinical trials. The patient as an actor emerged as an important factor. Hence, factors both at organizational and individual levels influenced the prescribing of biological drugs. The factors should not be seen as individual influences but were described as influencing prescription in an interactive, nonlinear way. CONCLUSIONS: Potential factors explaining differences in prescription practice are experience and perception of the evidence on the individual level and the structure of the department and participation in clinical trials on the organizational level. The influence of patient attitudes and preferences and interpretation of scientific evidence seemed to be somewhat contradictory in the qualitative responses as compared to the quantitative rating, and this needs further exploration. An implication of the present study is that in addition to scientific knowledge, attempts to influence prescription behavior need to be multifactorial and account for interactions of factors between different actors.
25367672 Intra-individual assessment of inflammatory severity and cartilage composition of finger j 2015 Apr OBJECTIVE: To intra-individually assess the association of inflammation severity and cartilage composition measured by RAMRIS synovitis sub-score and delayed gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC) of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA). METHODS: Forty-three patients with RA according to ACR/EULAR classification criteria (age 52.9 ± 14.5 years, range, 18-77 years) were included in this study. All study participants received 3-T MRI scans of the metacarpophalangeal joints of the second and third finger (MCP 2 and 3). The severity of synovitis was scored according to the RAMRIS synovitis sub-score by two readers in consensus. In the cases with identical synovitis sub-scores, two radiologists decided in consensus on the joint with more severe synovitis. Cartilage composition was assessed with dGEMRIC. To test the association of inflammation severity and cartilage damage and in order to eliminate inter-patient confounders, each patient's MCP 2 and 3 were dichotomized into the joint with more severe synovitis versus the joint with less severe synovitis for a paired Wilcoxon test of dGEMRIC value. RESULTS: There was a significant difference of dGEMRIC value (median of difference: 47.12, CI [16.6; 62.76]) between the dichotomized MCPs (p = 0.0001). There was a significant correlation between dGEMRIC value and RAMRIS synovitis grading of the joint with more severe synovitis (r = 0.5; p < 0.05) and the joint with less severe synovitis (r = 0.33; p < 0.05). CONCLUSIONS: Our data concur with the concept that synovitis severity is associated with cartilage damage. The local inflammatory status on a joint level correlated significantly with the extent of cartilage degradation in biochemical MRI.
23604731 Frequency and predictors for falls in the ambulatory patients with rheumatoid arthritis: a 2013 Oct The aim of this multicentre study is to investigate the incidence and risk factors for falls in ambulatory rheumatoid arthritis (RA) patients. One hundred and eighty-five ambulatory RA patients who have been followed up in 3 different centres were included in study. Patients were a part of Turkish League Against Rheumatism-Follow-up Program. All patients were evaluated at the baseline in terms of demographic features, falls history in the last year, disease-specific characteristics and co-morbidities. Functional status was evaluated by chair stand test with five repetitions and heel-toe walking. Erythrocyte sedimentation rate and CRP values were measured. Study patients were followed by the three monthly visits during a year. Patients were asked to fill the fall diary and/or call the doctor when a fall happens. The features of falls were recorded to the files at the time of the fall. The mean age was 56.7 ± 11.4 years. Four patients were drop out the study. Thirty-four patients fell and 2 had fractures during 1 year. Falls were found to be correlated with age, visual analogue score for pain, previous falls, use of assistive devices for ambulation, use of two or more medications and ability to do heel-toe walking. In the multivariate regression analysis, previous falls and use of assistive device for ambulation were found to be independent risk factors for falls (p = 0.004 OR 3.3 95 % CI 1.5-7.4, p = 0.001 OR 6.2 95 % CI 2-19.1). Fall history in the last year and using an assistive ambulation device are the predictors of the falls.
24028567 Predicting persistent inflammatory arthritis amongst early arthritis clinic patients in th 2013 INTRODUCTION: Analyses of large clinical datasets from early arthritis cohorts permit the development of algorithms that may be used for outcome prediction in individual patients. The value added by routine use of musculoskeletal ultrasound (MSUS) in an early arthritis setting, as a component of such predictive algorithms, remains to be determined. METHODS: The authors undertook a retrospective analysis of a large, true-to-life, observational inception cohort of early arthritis patients in Newcastle upon Tyne, UK, which included patients with inflammatory arthralgia but no clinically swollen joints. A pragmatic, 10-minute MSUS assessment protocol was developed, and applied to each of these patients at baseline. Logistic regression was used to develop two "risk metrics" that predicted the development of a persistent inflammatory arthritis (PIA), with or without the inclusion of MSUS parameters. RESULTS: A total of 379 enrolled patients were assigned definitive diagnoses after ≥12 months follow-up (median 28 months), of whom 162 (42%) developed a persistent inflammatory arthritis. A risk metric derived from 12 baseline clinical and serological parameters alone had an excellent discriminatory utility with respect to an outcome of PIA (area under receiver operator characteristic (ROC) curve 0.91; 95% CI 0.88 to 0.94). The discriminatory utility of a similar metric, which incorporated MSUS parameters, was not significantly superior (area under ROC curve 0.91; 95% CI 0.89 to 0.94). Neither did this approach identify an added value of MSUS over the use of routine clinical parameters in an algorithm for discriminating PIA patients whose outcome diagnosis was rheumatoid arthritis (RA). CONCLUSIONS: MSUS use as a routine component of assessment in an early arthritis clinic did not add substantial discriminatory value to a risk metric for predicting PIA.
25005327 Efficacy of golimumab plus methotrexate in methotrexate-naïve patients with severe active 2014 Sep The purpose of this study was to assess the treatment benefit of golimumab + methotrexate (MTX) vs. MTX monotherapy in MTX-naïve patients with severe active rheumatoid arthritis (RA). This was a post hoc analysis of MTX-naïve RA patients in the GO-BEFORE trial who were randomized to receive placebo + MTX (n = 160), golimumab 50 mg + MTX (n = 159), or golimumab 100 mg + MTX (n = 159). Subsets of patients with severe disease were identified using these baseline criteria: C-reactive protein (CRP) ≥1.5 mg/dL, CRP ≥3.0 mg/dL, swollen joint count (SJC) ≥10 and tender joint count (TJC) ≥12, SJC ≥ 20/TJC ≥ 12, 28-joint count Disease Activity Score using CRP (DAS28-CRP) >5.1, and anti-cyclic citrullinated peptide antibody-positive status. The treatment effect of golimumab + MTX vs. MTX alone was evaluated for these outcomes: the proportions of patients achieving ≥20, 50, and 70 % improvement in the American College of Rheumatology criteria; DAS28-CRP European League Against Rheumatism response; DAS28-CRP <2.6, clinically meaningful improvement in physical function; and change in van der Heijde-Sharp score ≤0 at week 52. Clinical response was greater in the golimumab + MTX groups vs. placebo + MTX for all of the outcomes evaluated. Furthermore, the treatment effect of golimumab + MTX was consistently greater among patients in the severe disease subsets when compared with the overall GO-BEFORE trial population. The treatment benefit of golimumab + MTX vs. MTX monotherapy was most pronounced within the subsets of patients with CRP ≥3.0 mg/dL and SJC ≥ 20/TJC ≥ 12. Following treatment with golimumab + MTX, improvements in RA signs/symptoms and in progression of structural damage were evident for the overall GO-BEFORE population, with the treatment effect more pronounced among patients with severe active disease.
23452206 Cigarette smoke condensate extracts induce IL-1-beta production from rheumatoid arthritis 2013 Jun Cigarette smoking is a major established environmental risk factor for rheumatoid arthritis (RA), and synoviocyte-derived proinflammatory cytokines are implicated in the pathogenesis of RA. We have reported that aryl hydrocarbon or cigarette smoke condensate (CSC) is able to upregulate the production of proinflammatory cytokines from an RA patient-derived synovial fibroblast cell line MH7A. In this study, we compared the effect of CSC on induction of interleukin-1β (IL-1β) from RA or osteoarthritis (OA) patient-derived synovial fibroblasts, and studied the mechanism of the effect of CSC. CSC induced IL-1β mRNA from RA patient-derived synoviocytes and MH7A, but not from OA patient-derived synoviocytes. CSC induced the mRNA and both precursor and mature forms of IL-1β, and caspase-1 activity in MH7A. The mechanism of CSC-induced IL-1β mRNA expression was investigated in MH7A. Reporter gene analyses and promoter pull-down assay indicated that 3 novel NF-κB sites at -3771 to -3762 bp, -3105 to -3096 bp, and -2787 to -2778 bp in the promoter region of the IL-1β gene, especially the far distal NF-κB site and NF-κB activation, are critical for the gene activation by CSC. CSC-induced NF-κB activation, IL-1β promoter activity, IL-1β mRNA upregulation, and CYP1A1 mRNA induction were all inhibited by an aryl hydrocarbon receptor (AhR) antagonist α-naphthoflavone. These results indicate that CSC induced IL-1β production from RA patient-derived synoviocytes, but not OA patient-derived synoviocytes, through AhR-dependent NF-κB activation and novel NF-κB sites.
25240430 Sense of coherence and self-sacrificing defense style as predictors of psychological distr 2015 Apr Individual differences in adjustment during a disease's course determine psychological response and outcome. This study aimed to investigate prospectively whether coping with health stressors and self-sacrificing defense style could predict psychological adjustment and health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA). Seventy-four consecutive RA patients attending a rheumatology clinic were assessed for psychological distress (SCL-90-R), sense of coherence (SOC scale), self-sacrificing defense style (Defense Style Questionnaire-88), disease activity (DAS-28), pain, disability (Health Assessment Questionnaire) and HRQoL (World Health Organization Quality of Life Instrument, Short Form) at baseline and 5 years later. Multiple regression and moderator analyses were carried out. The results showed that disease activity (p < .001), pain (p = .005), psychological distress (p = .031), social relations HRQoL (p = .042) and environment HRQoL (p = .020) significantly improved over time. SOC was found an independent predictor of improvement in psychological distress (p = .003), overall general health (p = .002) and social relations HRQoL (p = .004); self-sacrificing independently predicted environment HRQoL (p = .042). The self-sacrificing defense style moderated the relationships between improvement in pain and improvement in overall general health (p = .024) and between improvement in pain and improvement in social relations HRQoL (p = .006). These findings indicate that, in RA, SOC predicts improvement in psychological distress and HRQoL over time, while a self-sacrificing defense style moderates the relationship of pain with HRQoL in the long term. These variables may partly explain inter-individual differences in adaptation to RA. Therefore, the design of psychotherapeutic trials targeting the patients' defensive profiles and coping with health stressors capacities is an important research perspective.
23582631 Pathway analysis of genome-wide association studies on rheumatoid arthritis. 2013 Jul OBJECTIVES: The aims of this study were to identify candidate single nucleotide polymorphisms (SNPs) and candidate mechanisms of RA and generate hypotheses for SNP 'gene' pathways. METHODS: We used a meta-analysis dataset of rheumatoid arthritis (RA) genome-wide association studies (GWAS) which included 2,554,714 SNPs in 5,539 RA cases and 20,169 controls of European descent. ICSNPathway (Identify candidate Causal SNPs and Pathways) analysis was applied to the meta-analysis results of the RA GWAS dataset. RESULTS: ICSNPathway analysis identified 49 candidate SNPs included in 37 candidate pathways. The top 5 candidate causal SNPs, rs1063478 (p=5.40E-09), rs 375256 (p=3.44E-09), rs365066 (p=3.60E-30), rs2581 (p=2.7E-25), and rs1059510 (p=2.52E-06) were all at human leukocyte antigen (HLA) loci. These candidate SNPs and pathways provided 22 hypothetical biological mechanisms. The most strongly associated pathway concerned HLA: rs1063478 alters the role of HLA-DMA in the context of the pathway of antigen processing and presentation of peptide antigen. ICSNPathway analysis identified two candidate non-HLA SNPs included in ten candidate pathways, which provided two hypothetical biological mechanisms. First, rs2476601 alters the role of protein tyrosine phosphatase non-receptor 22 (PTPN22) in the context of immune response-activation cell surface receptor signalling pathway, and, rs2230926 alters the role of tumour necrosis factor-alpha-induced protein 3 (TNFAIP3) in the context of the CD40L signalling pathway. CONCLUSIONS: The application of ICSNPathway analysis to the meta-analysis results of RA GWAS datasets indicated candidate SNPs and pathways involving HLA-DMA, PTPN22, and TNAIP3 associated with RA susceptibility.
24246254 Epstein-Barr virus-positive oral ulceration simulating Hodgkin lymphoma in a patient treat 2014 Apr Immunosuppressive therapy for patients diagnosed with rheumatoid arthritis has long been implicated in the development of various neoplastic processes, including leukemia and lymphoma. Methotrexate is a commonly administered antimetabolic medication thought to improve the symptoms of rheumatoid arthritis through its anti-inflammatory effects. Longterm methotrexate therapy and concurrent rheumatoid arthritis have both been independently suggested as risk factors for developing lymphoma. The mechanism has been theorized to be severe immunosuppression and an increased frequency of latent infection with pro-oncogenic viruses, such as the Epstein-Barr virus (EBV). Spontaneous remission of these malignancies has been seen after discontinuation of the methotrexate therapy. In the present study, we report the case of a patient diagnosed with rheumatoid arthritis and treated with methotrexate and prednisone. She developed intraoral ulcerations that histopathologically resembled Hodgkin's lymphoma.