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ID PMID Title PublicationDate abstract
23098925 Linking systemic angiogenic factors (VEGF, angiogenin, TIMP-2) and Doppler ultrasound to a 2013 May OBJECTIVE: To evaluate an association between synovial Doppler flow and serum levels of vascular endothelial growth factor (VEGF), angiogenin and TIMP-2 in patients with rheumatoid arthritis during anti-inflammatory treatment with glucocorticoids and TNF-α inhibitors. METHODS: Inflamed wrists of 15 patients with rheumatoid arthritis (RA) were examined by two independent ultrasound investigators prior to and at days 3, 7, 14 and 42 after the initiation of treatment with glucocorticoids in therapy-naïve patients or after the beginning of a therapy with a TNF-α inhibitor in patients with DMARD failure. Quantitative three-dimensional power Doppler ultrasonographic assessment of synovial vascularization was compared at each visit with serum levels of VEGF, angiogenin and TIMP-2. RESULTS: In the glucocorticoid group, synovial Doppler signals decreased significantly at day 3 (-44%; P=0.003) in comparison to a delayed decrease in the TNF-α inhibitor group after 6 weeks (-46%; P=0.001). A significant reduction of serum VEGF levels could be determined with a delay of 1 week after the decrease of Doppler activity but no correlation was found between both parameters (rho: P=0.7; r=-0.03). Angiogenin concentrations decreased in the TNF group and increased in the GC group. Levels of TIMP-2 did not change significantly in both groups. CONCLUSION: The decrease of serum VEGF levels under treatment with glucocorticoids or TNF-α inhibitors followed the reduction of the intra-articular synovial Doppler flow. This result supports the idea that the reduction of synovial perfusion due to anti-inflammatory treatment is not regulated by systemic VEGF, but that the inflamed joints are the source for circulating VEGF.
21780650 [Methotrexate-induced changes in the concentration of antibodies to mutaded citrullinated 2011 AIM: To study effects of methotrexate on the titer of antibodies to mutated citrullinated vimentin (anti-MCV) and ascertain possibility of using this marker for control of treatment results and choice of individual effective dose of the drug. MATERIAL AND METHODS: A 12-month trial included 76 patients with verified rheumatoid arthritis (RA). Methotrexate per os was given in a dose 7.5-10 mg/week to 44 (57.9%) patients, 25 patients received no basic therapy. Anti-MCV (IU/ml) were detected with commercial chemicals made in Germany (ORGENTEC). RESULTS: RA patients given methotrexate doses 7.5 and 10 mg/week and untreated with basic anti-inflammatory drugs showed no significant differences by basic clinical and device parameters, level of anti-MCV at primary examination and 12 months later. CONCLUSION: Anti-MCV titer cannot be used for control of efficacy of methotrexate treatment in doses 75 and 10 mg/week, choice of individual effective doses.
21953083 Presumptive role of 129 strain-derived Sle16 locus in rheumatoid arthritis in a new mouse 2011 Oct OBJECTIVE: Fcγ receptor type IIb (FcγRIIb) is a major negative regulator of B cells, and the lack of FcγRIIb expression has been reported to induce systemic lupus erythematosus (SLE) in mice of the C57BL/6 (B6) genetic background. The 129 strain-derived Sle16 locus on the telomeric region of chromosome 1 including polymorphic Fcgr2b confers the predisposition to systemic autoimmunity when present on the B6 background. We undertook this study to examine the effect of the Sle16 locus on autoimmune disease in FcγRIIb-deficient B6 mice. METHODS: We established 2 lines of FcγRIIb-deficient B6 congenic mouse strains (KO1 and KO2) by selective backcrossing of the originally constructed FcγRIIb-deficient mice on a hybrid (129×B6) background into a B6 background. Although both lack FcγRIIb expression, the KO1 and KO2 strains carry different lengths of the 129 strain-derived telomeric chromosome 1 segment flanked to the null-mutated Fcgr2b gene; the KO1 strain carries a 129 strain-derived ∼6.3-Mb interval distal from the null-mutated Fcgr2b gene within the Sle16 locus, while this interval in the KO2 strain is of B6 origin. RESULTS: Unexpectedly, both strains failed to develop SLE; instead, the KO1 strain, but not the KO2 strain, spontaneously developed severe rheumatoid arthritis (RA) with an incidence reaching >90% at age 12 months. CONCLUSION: The current study shows evidence that the epistatic interaction between the Fcgr2b-null mutation and a polymorphic gene(s) in the 129 strain-derived interval located in the distal Sle16 locus contributes to RA susceptibility in a new mouse model with the B6 genetic background, although the participation of other genetic polymorphisms cannot be totally excluded.
21607552 Current smoking status is associated to a non-ACR 50 response in early rheumatoid arthriti 2011 Dec The purpose of this study is to determine factors associated with a non-ACR 50 response at 6 months of follow-up, in a cohort of patients with early rheumatoid arthritis (RA). Early RA patients (symptom duration <1 year), treated with the same combination treatment (methotrexate and sulfasalazine), were included. Demographic characteristics of the patients including current smoker status (defined as a patient that smokes at least one cigarette per day), years of formal education, a 28-joint count for swelling and tenderness were registered. A basal HAQ questionnaire, visual scales for global assessment, and pain were answered by all patients, and a CDAI basal score was calculated. The ACR 50 response was determined at 6 months follow-up. Multivariable logistic regression analysis was used to calculate adjusted ORs. Two hundred twenty-five patients were evaluated, but only 144 had a complete follow-up, 43% of the latter did not reach an ACR 50 response. The only factor associated with this outcome was current smoking (OR 3.58, P < 0.008, 95% CI 1.23-11.22). Low level of formal education (≤6 years) had a tendency towards a statistical difference (P < 0.08). After controlling with low level of formal education, sex, age in years, and CDAI baseline value with multivariable logistic regression analysis, current smoking status had an adjusted OR of 3.91 (P < 0.009, 95% CI 1.41-10.81). Smoking is associated with a non-ACR 50 response in early rheumatoid arthritis in patients treated with a combination therapy with methotrexate and sulfasalazine.
22076944 Which dimensions of fatigue should be measured in patients with rheumatoid arthritis? A De 2012 Mar OBJECTIVE: Rheumatoid arthritis (RA) patients experience fatigue as a multidimensional symptom. The aim of the present study was to use health professionals and patients alike to identify which dimensions of fatigue should be measured in RA. METHODS: Twelve fatigue dimensions were constructed, based on items from traditional questionnaires and items generated from interviews. Health professionals and patients evaluated these dimensions, related to an initial pool of 294 items, in a Delphi procedure. Dimensions were selected if rated important by at least 80% of the participants. RESULTS: Ten rheumatologists, 20 nurses and 15 patients participated. All fatigue dimensions were selected directly (severity, frequency, duration, changes in fatigue, perceived causes of fatigue, energy, sleep/rest, body feeling, cognition/concentration, coping, negative emotions/mood and consequences). No additional dimensions emerged from participants' comments and suggestions. CONCLUSIONS: This study revealed 12 fatigue dimensions. This underlines the multidimensionality of fatigue in RA and the need for comprehensive measurement.
21863465 [Ultrasound-guided joint injections in patients with rheumatic diseases]. 2011 Aug Joint and soft tissue injections are routinely performed in daily rheumatology practice to establish the diagnosis or as part of the treatment in patients suffering from rheumatic diseases. Consequently, joint injections have been included in the rheumatology further training curriculum. Despite numerous studies demonstrating a poor accuracy and outcome of joint injections guided only by clinical examination, most of the injection procedures are still performed in a "blind" fashion based on clinical judgment. Ultrasound has evolved as an established imaging method in rheumatology within the past decade and is considered the preferred imaging modality for joint interventions due to its availability and lack of radiation exposure. In this article the indications and important aspects of the practical management of ultrasound-guided injections performed in daily rheumatology practice are summarized.
21267570 Anti-PAD4 autoantibodies in rheumatoid arthritis: levels in serum over time and impact on 2012 May Isoform 4 of the human peptidylarginine deiminase (hPAD4) enzyme may be responsible for the citrullination of antigens in rheumatoid arthritis (RA) and has been shown to be itself the target of disease-specific autoantibodies. Here, we have tested whether the level of serum anti-hPAD4 antibodies in RA patients is stable over a period of 10 years and whether the antibodies influence hPAD4-mediated deimination of the small substrate N-α-benzoyl-L-arginine ethyl ester. RA sera (n = 128) obtained at baseline and after 10 years were assessed for anti-hPAD4 antibodies by a specific immunoassay. For 118 RA patients, serum anti-hPAD4 IgG levels were stable over 10 years. Seven patients who were negative for anti-PAD4 IgG at baseline had become positive after 10 years. Further, total IgG from selected RA patients and controls were purified, and a fraction was depleted for anti-hPAD4 antibodies. Kinetic deimination assays were performed with total IgG and depleted fractions. The k ( cat ) and K ( m ) values of hPAD4-mediated deimination of N-α-benzoyl-L-arginine ethyl ester were not affected by the depletion of the anti-hPAD4 antibodies from the total IgG pool. In conclusion, RA patients remain positive for anti-hPAD4 antibodies over time and some patients who are initially anti-hPAD4 negative become positive later in the disease course. The anti-hPAD4 antibodies did not affect the enzymatic activity of hPAD4 when the small substrate N-α-benzoyl-L-arginine ethyl ester was used. However, this finding may not exclude an effect of these autoantibodies on citrullination of protein substrates in RA.
22697086 Absence of xenotropic murine leukemia virus-related virus in Italian patients affected by 2012 Apr The xenotropic murine leukemia virus-related virus (XMRV) has been recently linked to chronic fatigue syndrome in a US cohort in whom the virus was demonstrated in 67% patients vs 3.7% healthy controls. Albeit this finding was not substantiated by subsequent reports and eventually considered a laboratory contamination, the matter is still the object of intense debate and scrutiny in various cohorts of patients. In this work we examined well-clinically characterized Italian patients affected by chronic fatigue syndrome, and also fibromyalgia and rheumatoid arthritis, two chronic illnesses of basically unknown etiology which show quite a few symptoms in common with chronic fatigue syndrome. Although we used recently updated procedures and controls, the XMRV was not found in 65 patients with chronic fatigue syndrome diagnosis, 55 with fibromyalgia, 25 with rheumatoid arthritis, nor in 25 healthy controls. These results add to the ever-growing number of surveys reporting the absence of XMRV in chronic fatigue syndrome patients and suggest that the virus is also absent in fibromyalgia and rheumatoid arthritis.
23092068 Gamma heavy chain disease in a patient with rheumatoid arthritis--a laboratory evaluation. 2012 INTRODUCTION: Heavy chain diseases (HCD) are neoplastic proliferations of B cells which secrete truncated immunoglobulin heavy chains without associated light chains. Being rare and probably underdiagnosed diseases the aim of this report is to show an additional case of gamma heavy chain disease in a 48 year old female patient with rheumatoid arthritis focusing on the laboratory presentation. MATERIALS AND METHODS: Laboratory work-up included agarose gel electrophoresis (AGE), capillary zone electrophoresis (CZE), immunofixation and nephelometrically determined immunoglobulin and immunoglobulin subclasses of the patient's serum. Urine samples were also subjected to immunofixation and to a SDS-PAGE with consecutive immunoblot. RESULTS: Nephelometrically measured elevated IgG concentrations were noted in combination with a decreased gamma globulin region and an increased beta globulin region on AGE. A definite monoclonal spike was not identified on AGE but at least suspected on CZE; finally serum and urine immunofixation demonstrated a monoclonal gamma heavy chain devoid of any corresponding light chains confirming the diagnosis of HCD. Analysis of the gamma heavy chain (HC) with means of SDS-PAGE revealed proteins of 40 kD and 80 kD most likely presenting a truncated HC in its monomeric and dimeric form and possibly leading to the failure of IgG-subclass typing with the applied IgG subclass antisera. CONCLUSION: This case report illustrates a new case of gamma HCD demonstrating variable laboratory manifestations and therefore the need for heightened awareness concerning this disease when confronted with abnormal and discrepant protein profiles in routinely applied laboratory tests.
22039167 Level of agreement of the 1987 ACR and 2010 ACR/EULAR rheumatoid arthritis classification 2012 Mar BACKGROUND: In 2010, new classification criteria for rheumatoid arthritis (RA) were developed. OBJECTIVE: To assess agreement between 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria and the potential source of discordance, based on ESPOIR cohort data. METHODS: 813 early arthritis patients were included in ESPOIR between 2002 and 2005. Between-criteria agreement was based on the κ coefficient. Discordance was explored by logistic regression. RESULTS: Data for 811 patients were available, with their main characteristics as follows: women 77%, swollen joint count 7.2, tender joint count 8.4, disease activity score in 28 joints 5.2, rheumatoid factor 46%, anticitrullinated protein antibody (ACPA) 39%, structural damage 22%. At baseline, 579 (71.4%) patients met the 1987 ACR criteria and 641 (79.0%) the 2010 criteria. Agreement at baseline was discordant for 168 patients: 115 satisfied the 2010 criteria and 53 the 1987 criteria. Concordance between the two sets was fair, with a κ coefficient of 0.45 and 0.42 at baseline and year 2, respectively. The main sources of discordance were the number and symmetry of joint involvement, as well as ACPA status. CONCLUSION: 2010 ACR/EULAR criteria identified more patients with RA than did 1987 criteria. The 2010 criteria failed to identify RA patients with symmetrical seronegative arthritis and limited joint involvement.
22895480 Incidence and aggravation of cervical spine instabilities in rheumatoid arthritis: a prosp 2012 Dec 15 STUDY DESIGN: A prospective minimum 5-year follow-up study of the cervical spine in patients with rheumatoid arthritis (RA) initially without cervical involvement. OBJECTIVE: To clarify the incidence and aggravation of cervical spine instabilities and their predictive risk factors in patients with RA. SUMMARY OF BACKGROUND DATA: Many reports have shown the progression of cervical spine involvement in RA. However, few articles have described comprehensive evaluation of its prognostic factors. METHODS: A total of 140 patients with "definite" or "classical" RA initially without cervical involvement were prospectively followed for more than 5 years. Radiographical cervical findings were classified into 3 instabilities: atlantoaxial subluxation (AAS: atlantodental interval >3 mm), vertical subluxation (VS: Ranawat value <13 mm), and subaxial subluxation (SAS: irreducible translation ≥ 2 mm). "Severe" extents were defined as AAS with atlantodental interval 10 mm or more, VS with Ranawat value 10 mm or less, and SAS with translation 4 mm or more or at multiple levels. Incidence of these developments and predictors for "severe" instabilities were investigated. RESULTS: During 6.0 ± 0.5 years, 43.6% of 140 patients developed cervical instabilities: AAS in 32.1%, VS in 11.4%, and SAS in 16.4% with some combinations. "Severe" instabilities were exhibited in 12.9% of patients: AAS in 3.6%, VS in 6.4%, and SAS in 5.0%. Furthermore, 4.3% presented canal stenosis, with 13 mm or less space available for the spinal cord (SAC) due to "severe" AAS or "severe" VS in 2.9% and 12 mm or less SAC due to "severe" SAS in 2.1%. Multivariable logistic regression analysis identified corticosteroid administration, mutilating changes at baseline, and the development of nonmutilating into mutilating changes during the follow-up period correlated with "severe" instabilities (P < 0.05). CONCLUSION: A minimum 5-year follow-up reveals the occurrence of cervical instabilities in 43.6%, "severe" aggravation in 12.9%, and decreased SAC in 4.3% of patients with RA. Characteristics of severe disease activity-established mutilating changes, progressive development into mutilating changes, and potentially concomitant corticosteroid treatment-are indicators for poor prognosis of the cervical spine in RA.
22243554 Fibromyalgia in patients with rheumatoid arthritis: driven by depression or joint damage? 2011 Nov OBJECTIVES: Studies have shown an increased incidence of fibromyalgia (FMS) in RA patients. The aims of this study were to explore the effect of mood and disease damage on the prevalence of FMS. METHODS: RA patients underwent a standardised clinical assessment, including disease activity (DAS-28), disease damage (mechanical joint score, MJS), fibromyalgia tender point assessment and the Hospital Anxiety and Depression Scale (HADS) and Health Assessment Questionnaire (HAQ). Patients were classified with FMS using two criteria a) tender-swollen joint count was ≥7 or b) tender point score of ≥11/18. RESULTS: 44/285 (15%) patients were classified as having FMS using the joint count difference of ≥7, compared to 18/285 (6%) using the tender point score of >11. Using the joint count difference to classify patients as having FMS, those with FMS had higher HAQ scores than those without FMS (2.12 vs. 1.5, p<0.0001). Although the DAS-28 was higher in this group (5.4 vs. 3.82, p<0.0001), the MJS was similar (8 vs. 7, p=0.19), suggesting similar levels of joint damage. Those classified as having FMS were more likely to have HAD-D scores of >11 (25% vs. 6%, p=0.0001). CONCLUSIONS: Coexistent FMS was common in our cohort, although using the tender point count to define FMS classified fewer patients with FMS. Within this group those with FMS had higher levels of depression but similar scores for joint damage indicating that in this cohort FMS and poorer physical functioning is mediated by low mood rather than joint damage.
21965639 Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate 2011 Dec OBJECTIVE: To determine the effects of changing from oral to subcutaneous (SC) methotrexate (MTX) in patients with rheumatoid arthritis (RA) on red blood cell MTX polyglutamate (RBC MTXGlu(n)) concentrations, disease activity, and adverse effects. METHODS: Thirty patients were changed from oral to SC MTX. Trough RBC MTXGlu(n) concentrations were measured for 24 weeks and concentrations fitted to a first-order accumulation model. Disease activity was assessed by 28-joint Disease Activity Score (DAS28). RESULTS: MTXGlu(3), MTXGlu(4), and MTXGlu(5) concentrations, but not MTXGlu(1) and MTXGlu(2), increased significantly over 24 weeks, reaching 90% of new steady-state concentrations by about 40 weeks. A decrease in DAS28 was associated with increased RBC MTXGlu(5) (p = 0.035) and RBC MTXGlu(3-5) (p = 0.032). No change in adverse effect frequency occurred. CONCLUSION: Changing to SC MTX results in increased long-chain MTXGlu(n). However, it takes at least 6 months for RBC steady-state concentrations to be achieved. Increased long-chain MTXGlu(n) concentrations were significantly associated with reduced disease activity.
21129157 Rheumatoid arthritis synovial fibroblasts produce a soluble form of the interleukin-7 rece 2011 Nov We previously demonstrated that baseline synovial overexpression of the interleukin-7 receptor α-chain (IL-7R) is associated with poor response to tumour necrosis factor (TNF) blockade in rheumatoid arthritis (RA). We found that IL-7R gene expression is induced in fibroblast-like synovial cells (FLS) by the addition of TNF-α, IL-1β and combinations of TNF-α+ IL-1β or TNF-α+ IL-17, thereby suggesting that these cytokines play a role in the resistance to TNF blockade in RA. Because FLS and CD4 T cells also produce a soluble form of IL-7R (sIL-7R), resulting from an alternative splicing of the full-length transcript, we wondered whether expression of sIL-7R is similarly regulated by pro-inflammatory cytokines. We also investigated whether sIL-7R is detectable in the serum of RA patients and associated with response to TNF blockade. RA FLS were cultured in the presence of pro-inflammatory cytokines and sIL-7R concentrations were measured in culture supernatants. Similarly, sIL-7R titres were measured in sera obtained from healthy individuals, early untreated RA patients with active disease and disease-modifying anti-rheumatic drug (DMARD)-resistant RA patients prior to initiation of TNF-blockade. Baseline serum sIL-7R titres were correlated with validated clinical measurements of disease activity. We found that exposure of RA FLS to pro-inflammatory cytokines (TNF-α, IL-1β and combinations of TNF-α and IL-1β or TNF-α and IL-17) induces sIL-7R secretion. Activated CD4 T cells also produce sIL-7R. sIL-7R serum levels are higher in RA patients as compared to controls. In DMARD-resistant patients, high sIL-7R serum concentrations are strongly associated with poor response to TNF-blockade. In conclusion, sIL-7R is induced by pro-inflammatory cytokines in RA FLS. sIL-7R could qualify as a new biomarker of response to therapy in RA.
22971639 A single nucleotide polymorphism of reduced folate carrier 1 predicts methotrexate efficac 2013   Methotrexate (MTX) exhibits large inter-individual and inter-ethnic differences in the dose required for its anti-rheumatic effect. To maintain low disease activity, patients may require increased MTX doses or co-administration of biologic disease-modifying anti-rheumatic drugs (bDMARDs). The availability of a marker predicting the effect of MTX will make it possible to increase the MTX dose and prescribe bDMARDs to patients at an early stage. To establish individualized medication for rheumatoid arthritis (RA), we investigated genetic polymorphisms of the folate pathway in Japanese RA patients. Eighty-nine patients were treated with MTX alone (MTX group). MTX and bDMARDs were co-administered to 81 patients because of insufficient MTX efficacy (MTX + bDMARDs group); an equally stable therapeutic effect was achieved in both groups. Polymorphism analyses using bDMARD co-treatment as the objective variable revealed a significant association between age and the G80A polymorphism of the reduced folate carrier 1 gene (RFC1) as an explanatory variable. Compared to patients with the A allele, patients with the G allele may have less intracellular MTX uptake and, therefore, poor efficacy; a greater number of them were found to be bDMARD concomitant cases. The results of this study suggest that the RFC1 G80A polymorphism may be a useful marker for predicting MTX efficacy in Japanese patients with RA.
20454961 Simplified approach to MR image quantification of the rheumatoid wrist: a pilot study. 2011 Jan OBJECTIVES: To determine an optimal threshold in a simplified 3D-based volumetry of abnormal signals in rheumatoid wrists utilizing contrast and non-contrast MR data, and investigate the feasibility and reliability of this method. MATERIALS AND METHODS: MR images of bilateral hands of 15 active rheumatoid patients were assessed before and 5 months after the initiation of tocilizumab infusion protocol. The volumes of abnormal signals were measured on STIR and post-contrast fat-suppressed T1-weighted images. Three-dimensional volume rendering of the images was used for segmentation of the wrist by an MR technologist and a radiologist. Volumetric data were obtained with variable thresholding (1, 1.25, 1.5, 1.75, and 2 times the muscle signal), and were compared to clinical data and semiquantitative MR scoring (RAMRIS) of the wrist. Intra- and interobserver variability and time needed for volumetry measurements were assessed. RESULTS: The volumetric data correlated favorably with clinical parameters almost throughout the pre-determined thresholds. Interval differences in volumetric data correlated favorably with those of RAMRIS when the threshold was set at more than 1.5 times the muscle signal. The repeatability index was lower than the average of the interval differences in volumetric data when the threshold was set at 1.5-1.75 for STIR data. Intra- and interobserver variability for volumetry was 0.79-0.84. The time required for volumetry was shorter than that for RAMRIS. CONCLUSIONS: These results suggest that a simplified MR volumetric data acquisition may provide gross estimates of disease activity when the threshold is set properly. Such estimation can be achieved quickly by non-imaging specialists and without contrast administration.
22594788 The role of inflammation and cardiovascular disease risk on microvascular and macrovascula 2012 May 17 INTRODUCTION: Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular disease (CVD), and it has been postulated that RA disease-related inflammation contributes to endothelial dysfunction. The aim of the present work was to examine predictors (RA-related and CVD risk factors) and anti-tumor necrosis factor-alpha (anti-TNF-α) treatment effects on endothelial function in different vascular beds. METHODS: Microvascular endothelial function (laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and macrovascular endothelial function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation) were analyzed in parallel with disease activity. Individual CVD risk factors and global CVD risk were assessed cross-sectionally in 99 unselected RA patients and longitudinally (baseline, 2 weeks, and 3 months) in 23 RA patients commencing anti-TNF-α therapy. RESULTS: In this cross-sectional study, regression analyses revealed that markers of RA disease-related inflammation were not associated with microvascular or macrovascular endothelium-dependent function (P > 0.05); global CVD risk inversely correlated with microvascular endothelium-dependent function (P < 0.01) and with macrovascular endothelium-independent function (P < 0.01). In the longitudinal study, only microvascular endothelium-dependent function showed an improvement after 2 weeks of anti-TNF-α treatment when compared with baseline (437% ± 247% versus 319% ± 217%; P = 0.001), but no association was evident between change in endothelial function and change in inflammatory markers. CONCLUSIONS: Classical CVD risk may influence endothelial function more than disease-related markers of inflammation in RA. Classical CVD risk factors and anti-TNF-α medication have different effects on microvascular and macrovascular endothelial function, suggesting that combined CVD-prevention approaches may be necessary. Prospective studies examining whether assessments of vascular function are predictive of long-term CV outcomes in RA are required.
21953215 Joint damage in rheumatoid arthritis progresses in remission according to the Disease Acti 2011 Dec OBJECTIVE: Remission has been defined as the ultimate target for patients with rheumatoid arthritis. The Disease Activity Score in 28 joints (DAS28) has been criticized for the amount of disease activity that remains in patients despite their achieving DAS28 remission. This study was undertaken to investigate the significance of residual inflammation in remission in relation to radiographic progression. METHODS: We pooled 1-year clinical data, kindly provided by the respective sponsors, on 864 patients in methotrexate monotherapy arms of recent pivotal trials. We identified patients who had attained persistent DAS28 remission from month 6 through month 12 (a DAS28(6-12) of <2.6). Among these patients we then assessed radiographic progression in total Sharp/van der Heijde scores (SHS) from baseline to 12 months between those with residual joint swelling (defined as a swollen joint count from month 6 through month 12 [SJC(6-12) ] of ≥2) and those without residual joint swelling (defined as an SJC(6-12) of <2). RESULTS: One hundred fourteen patients (13.2%) achieved a DAS28(6-12) of <2.6, of whom those without residual joint swelling (n = 92, 80.7%) had less radiographic progression over 1 year than those with residual joint swelling (n = 22, 19.3%) (mean ± SD SHS progression 0.2 ± 2.6 versus 2.2 ± 4.2; P = 0.11). Likewise, the proportion of patients with a total SHS progression of >0.5/year was significantly lower among those without joint swelling than among those with joint swelling (27.2% versus 50.0%; P = 0.039). DAS28 remitters without joint swelling showed progression comparable to that in the total group of remitters by the Simplified Disease Activity Index (remission defined as ≤3.3) and Clinical Disease Activity Index (remission defined as ≤2.8), namely, 0.2 versus -0.07 versus 0.16, respectively (P = 0.66). CONCLUSION: Radiographic progression with nonbiologic treatment is minimal only when patients in DAS28 remission have no persistent residual joint swelling. Under these conditions, progression is comparable to that in patients with disease in remission according to other disease activity indices.
22704786 Acute- or subacute-onset lung complications in treating patients with rheumatoid arthritis 2013 Aug Rheumatoid arthritis (RA) is a common systemic disease that manifests as inflammatory arthritis of multiple joints and produces a wide variety of intrathoracic lesions, including pleural diseases, diffuse interstitial pneumonia, rheumatoid nodules, and airway disease. Patients treated for RA can have associated lung disease that commonly manifests as diffuse interstitial pneumonia, drug-induced lung injury, and infection. The purpose of this pictorial review is to illustrate the radiographic and clinical features of lung complications of acute or subacute onset in patients treated for RA and to show the computed tomography features of these complications.
21864160 Interleukin-18: a mediator of inflammation and angiogenesis in rheumatoid arthritis. 2011 Oct Interleukin-18 (IL-18) is a highly regulated inflammatory cytokine that is elevated in synovial tissues and synovial fluids of patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (OA) and patients with other arthropathies. Within the RA joint, IL-18 can contribute to the inflammatory process by inducing leukocyte extravasation through upregulation of endothelial cell adhesion molecules, the release of chemokines from RA synovial fibroblasts, and directly as a monocytes, lymphocyte, and neutrophil chemoattractant. IL-18 can also help maintain and develop the inflammatory pannus by inducing endothelial cell migration and angiogenesis. IL-18 does this directly by binding and activating endothelial cells and indirectly by inducing RA synovial fibroblasts to produce angiogenic chemokines and vascular endothelial growth factor. IL-18 is present in RA synovial fluid in high levels, where it functions as an angiogenic mediator and leukocyte chemoattractant. IL-18 mediates all these inflammatory processes by binding to its receptor, IL-18 receptor, and initiating the activation of different signaling cascades leading to changes in target cells gene expression and behavior. IL-18 has been identified as a potential therapeutic target in the treatment of RA.