Structural Changes over a Short Period Are Associated with Functional Assessments in Rheumatoid Arthritis.

OBJECTIVE: To investigate the correlation between changes in radiological quantitative assessment with changes in clinical and functional assessment from baseline to 3 months in patients with rheumatoid arthritis (RA). METHODS: Twenty-eight patients with RA [methotrexate (MTX) and anti-tumor necrosis factor-α (TNF-α) group with high disease activity (n = 18); and MTX group with low disease activity (n = 10)] underwent assessments at baseline and 3 months: clinical [28-joint count Disease Activity Score (DAS28)], functional [Health Assessment Questionnaire (HAQ) and Michigan Hand Outcome Questionnaire (MHQ)], and imaging-based [3 Tesla magnetic resonance imaging (MRI) and high-resolution peripheral quantitative computed tomography (HR-pQCT)]. MR images were evaluated semiquantitatively [RA MRI scoring (RAMRIS)] and quantitatively for the volume of synovitis and bone marrow edema (BME) lesions. Erosion volumes were measured using HR-pQCT. RESULTS: After 3 months, the anti-TNF-α group demonstrated an improvement in disease activity through DAS28, HAQ, and MHQ. MRI showed significant decreases in synovitis and BME volume for the anti-TNF-α group, and significant increases in the MTX group. HR-pQCT showed significant decreases in bone erosion volume for the anti-TNF-α group, and significant increases in the MTX group. No significance was observed using RAMRIS. Changes in synovitis, BME, and erosion volumes, but not RAMRIS, were significantly correlated with changes in DAS28, HAQ, and MHQ. CONCLUSION: Quantitative measures were more sensitive than semiquantitative grading when evaluating structural and inflammatory changes with treatment, and were associated with patient clinical and functional outcomes. Multimodality imaging with 3T MRI and HR-pQCT may provide promising biomarkers that help determine disease progression and therapy response.

Association of High Anti-Cyclic Citrullinated Peptide Seropositivity and Lean Mass Index With Low Bone Mineral Density in Rheumatoid Arthritis.

OBJECTIVE: Osteoporotic fractures are associated with high morbidity and mortality. Persons with rheumatoid arthritis (RA) have twice the risk of osteoporosis-related fracture than age-matched controls, the causes for which remain unknown. We investigated contributions of RA characteristics, medication use, and body composition to low bone mineral density (BMD) in patients with RA. METHODS: Data were from the Arthritis, Body Composition, and Disability Study (n = 138; 82 women, 56 men). Demographic, clinical, laboratory, and functional variables were collected at study visits. Body composition (fat, lean muscle, and BMD) was measured by dual x-ray absorptiometry. Linear regression analyses evaluated the association between predictors and femoral neck BMD. RESULTS: Average disease duration was 19 years, 70% of patients were rheumatoid factor positive, and 55% were high-positive anti-cyclic citrullinated peptide (anti-CCP). Age and high anti-CCP positivity were negatively associated with BMD after controlling for other variables (ß = -0.003 and -0.055, respectively, P < 0.05). Appendicular lean mass index (ALMI) was positively associated with BMD (ß = 0.053, P < 0.0001). In high anti-CCP positivity participants, increasing anti-CCP levels were associated with a negative linear trend in BMD (ß = -0.011, P = 0.026). CONCLUSION: High anti-CCP positivity and ALMI were strongly associated with BMD in patients with RA. The linear relationship of anti-CCP levels with lower BMD supports the hypothesis that processes specific to RA negatively impact BMD. In contrast, ALMI was positively associated with BMD, emphasizing the importance of this potentially modifiable risk factor. Our findings highlight the complicated interplay of RA disease-specific and functional factors and their impact on bone mass.

Assessment of 3-month changes in bone microstructure under anti-TNFα therapy in patients with rheumatoid arthritis using high-resolution peripheral quantitative computed tomography (HR-pQCT).

BACKGROUND: Although one study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after TNFα inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment. We investigated the effects of 3-month anti-TNFα treatment on bone erosion progression and bone microarchitecture in RA patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Patients with RA (n = 27) (17 in the anti-TNFα and 10 in the MTX-only group) underwent assessment of disease activity score in 28 joints (DAS-28), radiographs, 3-T magnetic resonance imaging (MRI) and HR-pQCT of metacarpophalangeal and wrist joints at baseline and 3 months. HR-pQCT-derived erosion volume, joint volume/width and bone microarchitecture were computed and joint destruction was assessed using Sharp and RAMRIS scorings on radiographs and MRI, respectively. RESULTS: Overall, 73 erosions were identified by HR-pQCT at baseline. Over 3 months, the anti-TNFα group had decreased mean erosion volume; increased erosion volume was observed in one clinical non-responder. The MTX-only group in contrast, trended toward increasing erosion volume despite low disease activity. In the anti-TNFα group, joint-space width and volume of MCP joints decreased significantly and was positively correlated with erosion volume changes (R 2 = 0.311, p = 0.013; R 2 = 0.527, p = 0.003, respectively). In addition, erosion volume changes were significantly negatively correlated with changes in trabecular bone mineral density (R 2 = 0.353, p = 0.020) in this group. We observed significant correlation between percentage change in erosion volume and change in DAS-28 erythrocyte sedimentation rate and C-reactive protein CRP scores (R 2 = 0.558, p < 0.001; R 2 = 0.745, p < 0.001, respectively) in all patients. CONCLUSIONS: Using HR-pQCT, our data suggest that anti-TNFα treatment prevents erosion progression and deterioration of bone microarchitecture within the first 3 months of treatment, one patient not responding to treatment, had significant progression of bone erosions within this short time period. Patients with low disease activity scores (<3.2) can have continuous HR-pQCT-detectable progression of erosive disease with MTX treatment only. HR-pQCT can be a sensitive, powerful tool to quantify bone changes and monitor RA treatment short term (such as 3 months).

Neurologic Manifestations of Rheumatoid Arthritis.

Neurologic manifestations of rheumatoid arthritis (RA) range in severity from mild paresthesias in the hand from carpal tunnel syndrome to sudden death due to impingement of the medulla by an eroded, vertically subluxed dens. Most neurologic complications are a consequence of articular inflammation and damage that leads to compression of adjacent structures of the central or peripheral nervous systems. Rare but serious extra-articular manifestations include inflammation of the meninges and ischemic neuropathies due to necrotizing arteritis of the vasa vasorum. Medical therapy with synthetic disease-modifying antirheumatic drugs and biological agents has diminished the incidence of serious neurologic manifestations in RA.

Involvement of the Peripheral Nervous System in Polyarteritis Nodosa and Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis.

Peripheral nerve involvement is common in polyarteritis nodosa and the antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. The underlying mechanism is arteritis of the vasa nervorum, leading to ischemic neuropathy. The classic presentation is stepwise involvement of peripheral nerves with ongoing antecedent constitutional symptoms. This article reviews the pathologic findings, clinical syndromes, diagnosis, and treatment of ANCA-associated vasculitides.

Current Assays to Determine Free 25-Hydroxyvitamin D in Serum.

The 25-hydroxylated metabolite of vitamin D is the best clinical indicator of vitamin D status. For many years, emphasis has been on measuring total levels of 25-hydroxyvitamin D [25(OH)D], but recently, interest in measuring free 25(OH)D as a potentially better marker of vitamin D status has arisen. Since the 1980s when the first measurements of free 25(OH)D were made, little progress has been made in the development of rapid, reliable methods to determine the levels of free 25(OH)D. For many years, assessment of free 25(OH)D relied on calculations using levels of total 25(OH)D, albumin, and vitamin D binding protein (VDBP), for which many assays exist. However, because of vagaries in the measurement of VDBP in particular and the assumption of a constant affinity of VDBP for the vitamin D metabolites (which has been shown to be problematic), calculated values have proved suspect. This changed a few years ago when a new immunoassay was developed to measure free 25(OH)D directly. This review examines methods for determining free 25(OH)D, the different methods used in clinical studies, and the relationships between free 25(OH)D and other vitamin D metabolites and the physiologic functions affected by vitamin D metabolites, such as bone cell activity and turnover. The review also comments on the value of assessing free 25(OH)D and the efforts to standardize the assays.

Quantitative characterization of metacarpal and radial bone in rheumatoid arthritis using high resolution- peripheral quantitative computed tomography.

AIM: The objectives of this study were: (i) to develop a standardized method of quantifying bone mineral density (BMD) and microarchitecture in the hand and wrist bones of patients with rheumatoid arthritis (RA) using high resolution- peripheral quantitative computed tomography (HR-pQCT); (ii) to compare quantitative bone parameters between RA and post-menopausal osteopenic (PM-OP) subjects; and (iii) to correlate quantitative bone parameters at the distal radius with those at the metacarpal heads in RA subjects. METHODS: HR-pQCT imaging of the dominant hand and wrist was performed in 12 female RA patients. BMD and trabecular parameters for the 2-12% head region of the second and third metacarpals were calculated and compared between RA patients and healthy controls. Bone parameters were also calculated for 110 slices of the distal radius in RA patients and compared to data from controls and PM-OP women from a previous study. RESULTS: Compared to controls, RA patients had significantly decreased BMD, trabecular volume and number, and increased trabecular heterogeneity in the third metacarpal and distal radius. Significantly lower trabecular number and significantly higher ratio of outer annular trabecular BMD to inner trabecular BMD were observed in patients with RA, compared to patients with osteopenia (P < 0.05). Trabecular BMD in the third metacarpal and in the distal radius were significantly correlated (ρ = 0.918, P < 0.0001) in RA patients. CONCLUSION: This study established a standardized method for quantifying bone density and trabecular properties in the hand and wrist bones of RA patients using HR-pQCT. Deterioration of bone structure in RA patients was found comparable to that in osteopenic women, and trabecular bone loss near affected joints was found to be correlated with bone loss away from joints.

Efficiency Gains for Rheumatology Consultation Using a Novel Electronic Referral System in a Safety-Net Health Setting.

OBJECTIVE: Health information technology (HIT) holds promise in increasing access to rheumatologists by improving the quality and efficiency of referrals, but few studies have examined its use for this purpose. We evaluated the use and impact of a novel electronic referral (eReferral) system in rheumatology in a safety-net health system. METHODS: We examined eReferrals over 4 years. Our primary outcome was use of preconsultation exchange, defined as back-and-forth communication between referring and specialty care providers, facilitating triage of referrals, requests for more information, or resolution of questions without a visit. We calculated the proportion of eReferrals that underwent preconsultation exchange, time to reviewer response, and number of visits scheduled. To increase generalizability, we selected a random sample of eReferrals to undergo additional blinded, adjudicated review to assess agreement on appropriateness for preconsultation exchange. RESULTS: Between 2008 and 2012, 2,383 eReferrals were reviewed and 2,105 were eligible for analysis. One-fourth of eReferrals were resolved without a clinic visit. The proportion of eReferrals undergoing preconsultation exchange increased over time (55% in 2008 versus 74% in 2011), and the volume of referrals also steadily increased over time. Reviewer response time averaged between 1 and 4 days. In the random sample of eReferrals that underwent adjudicated review, agreement between reviewers was high (κ = 0.72). CONCLUSION: HIT-enabled preconsultation exchange was used for a majority of eReferrals and facilitated communication between referring clinicians and rheumatologists. This redesigned system of care allowed for triage of a high number of referrals, with many referrals determined to be appropriate for preconsultation exchange.

Correlation of structural abnormalities of the wrist and metacarpophalangeal joints evaluated by high-resolution peripheral quantitative computed tomography, 3 Tesla magnetic resonance imaging and conventional radiographs in rheumatoid arthritis.

AIM: In rheumatoid arthritis (RA) hands, we applied high-resolution peripheral quantitative computed tomography (HR-pQCT) and 3 Tesla (3 T) magnetic resonance imaging (MRI), which are new methods for erosion detection and bone marrow edema (BME) quantification. We compared the erosion measurements between these techniques with conventional radiographs (CR) in order to examine their significance for evaluating structural abnormalities. METHODS: In 16 RA patients, HR-pQCT of metacarpophalangeal and wrist joints, 3 T MRI of wrist joints, as well as CR in both hands and feet were performed. Ten patients had 1-year follow-up CR. CRs were graded according to the modified Sharp score (MSS). Bone erosions were evaluated in HR-pQCT and MRI. BME pattern was quantified from MRI for volume, signal change and total burden. RESULTS: The erosion detection sensitivity of MRI was 85.7% and CR was 60.9% when HR-pQCT was considered as a reference method. The smallest dimensions of erosion detected by HR-pQCT, MRI and CR were 0.09, 0.14 and 0.66 cm, respectively. Baseline total MSS was correlated with HR-pQCT erosion measures, MRI erosion measures and MRI BME volume (P < 0.05). The mean difference between baseline and 1-year follow-up MSS (delta MSS) was 1.2. A trend was observed toward a correlation between delta MSS and MRI BME volume and burden. CONCLUSION: This study demonstrates that HR-pQCT detects more and smaller bone erosions compared to MRI and CR. In addition, 3 T MRI can provide quantitative measurement of BME. Combination of HR-pQCT and MRI modalities may provide powerful tools to evaluate joint inflammation and bone damage in RA.

Pauci-immune glomerulonephritis in individuals with disease associated with levamisole-adulterated cocaine: a series of 4 cases.

Exposure to levamisole-adulterated cocaine can induce a distinct clinical syndrome characterized by retiform purpura and/or agranulocytosis accompanied by an unusual constellation of serologic abnormalities including antiphospholipid antibodies, lupus anticoagulants, and very high titers of antineutrophil cytoplasmic antibodies. Two recent case reports suggest that levamisole-adulterated cocaine may also lead to renal disease in the form of pauci-immune glomerulonephritis. To explore this possibility, we reviewed cases of pauci-immune glomerulonephritis between 2010 and 2012 at an inner city safety net hospital where the prevalence of levamisole in the cocaine supply is known to be high. We identified 3 female patients and 1 male patient who had biopsy-proven pauci-immune glomerulonephritis, used cocaine, and had serologic abnormalities characteristic of levamisole-induced autoimmunity. Each also had some other form of clinical disease known to be associated with levamisole, either neutropenia or cutaneous manifestations. One patient had diffuse alveolar hemorrhage. Three of the 4 patients were treated with short courses of prednisone and cyclophosphamide, 2 of whom experienced stable long-term improvement in their renal function despite ongoing cocaine use. The remaining 2 patients developed end-stage renal disease and became dialysis-dependent. This report supports emerging concern of more wide spread organ toxicity associated with the use of levamisole-adulterated cocaine.

Bone structure and perfusion quantification of bone marrow edema pattern in the wrist of patients with rheumatoid arthritis: a multimodality study.

OBJECTIVE: To quantify bone structure and perfusion parameters in regions of bone marrow edema pattern (BMEP), non-edematous bone marrow (NBM), and pannus tissue areas in the wrists of patients with rheumatoid arthritis (RA) using 3-Tesla (3T) magnetic resonance imaging (MRI), and high resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Sixteen subjects fulfilling American College of Rheumatology classification were imaged using a HR-pQCT system and a 3T MRI scanner with an 8-channel wrist coil. Coronal T2-weighted and dynamic contrast-enhanced (DCE-MRI) images were acquired. BMEP and pannus tissue areas were segmented semiautomatically in T2-weighted images. NBM areas were placed at a similar distance from the joint space as BMEP regions. MR and HR-pQCT images were registered, and bone variables were calculated within the BMEP and NBM regions. Perfusion parameters in BMEP, pannus tissue, and NBM regions were calculated based on the signal-time curve obtained from DCE-MRI. RESULTS: Eighteen BMEP areas were segmented, 15 of them presented proximal to pannus-filled erosions. Significant increases in bone density and trabecular thickness and number were observed in all BMEP regions compared to NMB (p < 0.05). Significantly elevated perfusion measures were observed in both BMEP and pannus tissue regions compared to NBM (p < 0.05). CONCLUSION: BMEP regions showed significantly increased bone density and structures as well as perfusion measures, suggesting bone remodeling and active inflammation. Combining MRI and HR-pQCT provides a powerful multimodality approach for understanding BMEP and erosions, and for potentially identifying novel imaging markers for disease progression in RA.

Quantitative in vivo HR-pQCT imaging of 3D wrist and metacarpophalangeal joint space width in rheumatoid arthritis.

In this technique development study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to non-invasively image and quantify 3D joint space morphology of the wrist and metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA). HR-pQCT imaging (82 µm voxel-size) of the dominant hand was performed in patients with diagnosed rheumatoid arthritis (RA, N = 16, age: 52.6 ± 12.8) and healthy controls (CTRL, N = 7, age: 50.1 ± 15.0). An automated computer algorithm was developed to segment wrist and MCP joint spaces. The 3D distance transformation method was applied to spatially map joint space width, and summarized by the mean joint space width (JSW), minimal and maximal JSW (JSW.MIN, JSW.MAX), asymmetry (JSW.AS), and distribution (JSW.SD)-a measure of joint space heterogeneity. In vivo precision was determined for each measure by calculating the smallest detectable difference (SDD) and root mean square coefficient of variation (RMSCV%) of repeat scans. Qualitatively, HR-pQCT images and pseudo-color JSW maps showed global joint space narrowing, as well as regional and focal abnormalities in RA patients. In patients with radiographic JSN at an MCP, JSW.SD was two-fold greater vs. CTRL (p < 0.01), and JSW.MIN was more than two-fold lower (p < 0.001). Similarly, JSW.SD was significantly greater in the wrist of RA patients vs. CTRL (p < 0.05). In vivo precision was highest for JSW (SDD: 100 µm, RMSCV: 2.1%) while the SDD for JSW.MIN and JSW.SD were 370 and 110 µm, respectively. This study suggests that in vivo quantification of 3D joint space morphology from HR-pQCT, could improve early detection of joint damage in rheumatological diseases.

Extraarticular manifestations of rheumatoid arthritis in a multiethnic cohort of predominantly Hispanic and Asian patients.

We conducted a study to determine the prevalence of extraarticular manifestations (ExRA) in a cohort of predominantly Hispanic and Asian patients with rheumatoid arthritis (RA), to identify factors associated with the development of ExRA, and to compare the prevalence of ExRA between Hispanic and Asian patients. Patients with RA followed in the outpatient rheumatology clinics of a public hospital were included if they were aged ≥18 years and met the 1987 American College of Rheumatology criteria for the diagnosis of RA. We performed a cross-sectional analysis in which patients with ExRA were identified based on predefined criteria. We compared sociodemographic and clinical characteristics in patients with and without ExRA. Multivariate logistic regression was used to examine the association between sociodemographic variables, clinical characteristics, and the presence of ExRA. The prevalence of ExRA was 21.5%, and the most common manifestations were subcutaneous nodules (17.2%) and interstitial lung disease (3.6%). Hispanic patients were significantly more likely to develop ExRA than Asian patients (odds ratio, 2.53; 95% confidence interval, 1.26-5.09). The development of ExRA was also associated with disease duration, male sex, and seropositivity for serum rheumatoid factor.

Quantitative and semiquantitative bone erosion assessment on high-resolution peripheral quantitative computed tomography in rheumatoid arthritis.

OBJECTIVE: To develop novel quantitative and semiquantitative bone erosion measures at metacarpophalangeal (MCP) and wrist joints in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT), and to correlate these measurements with disease duration and bone marrow edema (BME) patterns derived from magnetic resonance imaging (MRI). METHODS: Sixteen patients with RA and 7 healthy subjects underwent hand and wrist HR-pQCT and 3-Tesla MRI. Bone erosions of the MCP2, MCP3, and distal radius were evaluated by measuring maximal erosion dimension on axial slices, which is a simple and fast measurement, and then were graded (grades 0-3) based on the maximal dimension. Correlation coefficients were calculated between (1) sum maximal dimensions, highest grades, and sum grades of bone erosions; (2) erosion measures and the clinical evaluation; (3) erosion measures and BME volume in distal radius. RESULTS: The inter- and intrareader agreements of maximal erosion dimensions were excellent (intraclass correlation coefficients 0.89, 0.99, and root mean square error 9.4%, 4.7%, respectively). Highest grades and sum grades were significantly correlated to sum maximal dimensions of all erosions. Number of erosions, sum maximal erosion dimensions, highest grades, and sum grades correlated significantly with disease duration. Number of erosions, sum maximal dimensions, and erosion grading of the distal radius correlated significantly with BME volume. CONCLUSION: HR-pQCT provides a sensitive method with high reader agreement in assessment of structural bone damage in RA. The good correlation of erosion measures with disease duration as well as BME volume suggests that they could become feasible measures of erosions in RA.

A functional variant in FCRL3 is associated with higher Fc receptor-like 3 expression on T cell subsets and rheumatoid arthritis disease activity.

OBJECTIVE: CD4+FoxP3+ Treg cells suppress effector T cells and prevent autoimmune disease. Treg cell function is deficient in active rheumatoid arthritis (RA), a loss which may play a role in the pathogenesis of this disease. We previously showed that a single-nucleotide polymorphism in the FCRL3 gene led to higher expression of Fc receptor-like 3 (FcRL3) on Treg cells and that FcRL3+ Treg cells are functionally deficient in comparison to FcRL3- Treg cells. This study was undertaken to investigate the potential role of FcRL3 in RA. METHODS: A cross-sectional study was performed to evaluate the FCRL3 -169 genotype and FcRL3 expression on T cell subsets, including Treg cells, in peripheral blood samples from 51 patients with RA enrolled in the University of California, San Francisco (UCSF) RA Cohort. Clinical data were obtained from the UCSF RA Cohort database. RESULTS: Patients with the FCRL3 -169C allele (genotype C/C or C/T) expressed higher levels of FcRL3 on Treg cells, and on CD8+ and γ/δ T cells, in comparison to RA patients with the T/T genotype. Higher FcRL3 expression on these T cell subpopulations correlated with RA disease activity in patients harboring the FCRL3 -169C allele. Furthermore, FcRL3 expression on Treg cells was higher in patients with erosive RA, and the FCRL3 -169C allele was overrepresented in patients with erosive RA. CONCLUSION: Our findings indicate that FcRL3 expression, which is strongly associated with the presence of the FCRL3 -169C allele, may serve as a biomarker for RA disease activity.

Levels of plasma fibrinogen are elevated in well-controlled rheumatoid arthritis.

OBJECTIVE: Patients with RA have systemic inflammation and increased risk of cardiovascular (CV) events, including thrombosis. Levels of fibrinogen, a pro-thrombotic protein with predictive value for CV disease (CVD), are elevated during systemic inflammation. We compared circulating fibrinogen levels in patients with RA with healthy controls and evaluated the relationship with measures of disease activity. METHODS: Patients with RA and controls were recruited at the University of California, San Francisco (UCSF). Disease activity was evaluated using standard composite indices. Fibrinogen, ESR, serum CRP, acute-phase serum amyloid A and levels of selected cytokines were quantified. RESULTS: A total of 105 RA patients and 62 controls were studied. Among patients with RA, disease activity ranged from quiescent to highly active disease. Circulating fibrinogen levels were significantly higher in RA than in controls [median (interquartile range) 466 (391-575) vs 367 (309-419) mg/dl, respectively, P < 0.0001]. This difference remained highly statistically significant after adjustment for demographic variables and BMI. Although fibrinogen correlated significantly with clinical measures of disease activity, significantly elevated levels were observed at low levels of activity, even in RA patients with no detectable swollen or tender joints. In multivariable models, ~ 80% of the increased fibrinogen in RA was accounted for by increases in CRP and ESR. CONCLUSION: Circulating levels of fibrinogen are elevated in RA and correlated with markers of inflammation, but only modestly correlate with clinical assessments of disease activity. Even RA patients with excellent clinical disease control exhibit elevated levels compared with controls.

Rheumatoid arthritis: model of systemic inflammation driving atherosclerosis.

Similarities between the inflammatory pathways in atherosclerosis and rheumatoid arthritis (RA) are striking. Chronic systemic inflammation in RA patients leads to cardiovascular (CV) events beyond traditional cardiac risk factors. Clinicians typically focus on treating the joint manifestations of RA while neglecting to eliminate systemic inflammation, which leaves RA patients vulnerable to adverse CV events. In this review we provide an understanding of how systemic inflammation in RA accelerates atherosclerosis. This knowledge should guide therapeutic targets to minimize CV risk in RA, and may lead to insights into the inflammatory mechanisms of atherosclerosis in general.