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ID PMID Title PublicationDate abstract
19713205 A gain of function polymorphism in the interleukin 6 receptor influences RA susceptibility 2010 Jun OBJECTIVES: To investigate the possible role of a functional polymorphism in the soluble interleukin 6 receptor (sIL-6R) gene in the genetic background of rheumatoid arthritis (RA). METHODS: An association between disease status and the sIL-6R rs8192284 (A358D) variant was tested in 965 patients with RA and 988 unrelated healthy controls. Odds ratios (ORs) for disease were calculated with asymptotic 95% CI; p values <0.05 were considered statistically significant after adjustment for multiple testing. To determine the relationship between protein levels and IL-6R A358D genotype, the protein levels of sIL-6R in 100 plasma samples from healthy controls were measured using an ELISA and compared across the genotype groups. RESULTS: The allele frequency of the C allele (alanine) was lower in cases than in controls (38.4% vs 41.7%, p=0.04, OR 0.9, 95% CI 0.8 to 1.0), as were the CC/AC genotypes compared with AA genotype frequencies (61.0% in RA cases vs 67.5% in controls, p=0.004, OR 0.8, 95% CI 0.6 to 0.9). Plasma levels of sIL-6R differed significantly according to genotype in the controls: 17.00 + or - 2.03 ng/ml for A/A, 20.08 + or - 1.83 ng/ml for A/C and 21.57 + or - 2.10 ng/ml for C/C (p=0.0001). CONCLUSION: These data suggest a role for genetically determined lower sIL-6R levels as a risk factor for RA. The proinflammatory role of the IL6 system in established RA has been highlighted by the use of anti-sIL-6R antibodies. However, the findings of this study suggest a protective effect of IL6 on the risk of developing RA.
19493058 Th17 cells in rheumatoid arthritis and systemic lupus erythematosus. 2009 Jun Recent work has implicated a novel Th effector cell subset, the Th17 cell subset, in the development of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) because of the ability of Th17 cells to produce cytokines like IL-17 and IL-21 that can drive both inflammatory and humoral responses. In this review, we will discuss recent studies that have begun elucidating the factors that regulate the development of Th17 cells and provide a brief overview of the role of Th17 cells in RA and SLE.
20382605 The effect of anti-tumor necrosis factor (TNF)-alpha therapy with etanercept on endothelia 2010 Apr OBJECTIVE: To investigate the effects of tumor necrosis factor (TNF)- alpha antagonism with etanercept (ENC) on endothelial functions in patients with active rheumatoid arthritis (RA). METHODS: A total of 21 patients with RA were enrolled in this prospective study. Eleven of them (8 women, 3 men mean age 47.0+/-10.1 years) with high disease activity despite the conventional treatment were assigned to Group 1 and were given ENC treatment twice a week (25 mg SC injection) for 12 weeks. Ten patients with RA (8 women, 2 men mean age 55.0+/-6.4 years) under conventional methotrexate and prednisone therapy were assigned as Control group (Group 2). Endothelium-dependent and -independent vasodilator responses of the brachial artery were assessed by high-resolution ultrasound. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured at baseline and at the post treatment period. Mann-Whitney U and Wilcoxon tests were used to compare the data and correlation analysis was performed using Pearson correlation test. RESULTS: Endothelium-dependent vasodilatation improved from 5.2+/-0.8% to 7.9+/-1.3% (p=0.04) in ENC group, while no significant change was observed in the control group (from 6.6+/-1.1% to 7.0+/-1.8% p=0.67). No significant changes were found in endothelium-independent vasodilatation and baseline brachial artery diameters in both groups. A significant reduction in ESR and CRP were observed in patients receiving ENC (from 16.2+/-6.8 to 9.2+/-5.1 mm/h, p=0.003 and from 14.68+/-3.4 to 9.25+/-3.7 mg/L, p=0.003, respectively). CONCLUSION: Treatment with ENC for 12 weeks significantly improved endothelial function in patients with active RA compared to those under conventional therapy. The findings of the present study support the hypothesis that the use of TNF-alpha blockers in patients with active RA may reduce the high incidence of cardiovascular complications.
19888507 [The current role of ultrasound in the assessment of crystal-related arthropathies]. 2009 Jul Over last few years, the ultrasonography (US) generated an increasing popularity among rheumatologists due to excellent potentiality and numerous applications in rheumatology. Most of the published papers focus mainly to demonstrate the utility of US in early and chronic arthritis, short-term therapy monitoring and guidance for invasive procedures. Less attention has been paid to the potential of this technique in the field of crystal-related arthropathies. By virtue of the high resolution of "new generation" equipments, minimal crystal deposits can be detected even sometime when the radiography was negative. The aim of this paper was to present the principal findings in patients with crystal-related arthropathies.
19460157 Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor th 2009 INTRODUCTION: Anti-TNF therapies have revolutionized the treatment of rheumatoid arthritis (RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately one-third of patients demonstrate no clinical improvement in response to treatment with anti-TNF therapies, while another third demonstrate a partial response, and one-third an excellent and sustained response. Since no clinical or laboratory tests are available to predict response to anti-TNF therapies, great need exists for predictive biomarkers. METHODS: Here we present a multi-step proteomics approach using arthritis antigen arrays, a multiplex cytokine assay, and conventional ELISA, with the objective to identify a biomarker signature in three ethnically diverse cohorts of RA patients treated with the anti-TNF therapy etanercept. RESULTS: We identified a 24-biomarker signature that enabled prediction of a positive clinical response to etanercept in all three cohorts (positive predictive values 58 to 72%; negative predictive values 63 to 78%). CONCLUSIONS: We identified a multi-parameter protein biomarker that enables pretreatment classification and prediction of etanercept responders, and tested this biomarker using three independent cohorts of RA patients. Although further validation in prospective and larger cohorts is needed, our observations demonstrate that multiplex characterization of autoantibodies and cytokines provides clinical utility for predicting response to the anti-TNF therapy etanercept in RA patients.
19647146 Key symptom domains to be assessed in fibromyalgia (outcome measures in rheumatoid arthrit 2009 May This article discusses the key symptom domains to be assessed in fibromyalgia. Development of a consensus on a core set of outcome measures that should be assessed and reported in all clinical trials is needed to facilitate interpretation, pooling, and comparison of results. This aligns with the key objective of the Outcome Measures in Rheumatoid Arthritis Clinical Trials initiative to improve outcome measurement in rheumatic diseases through a data-driven interactive consensus process.
19179257 [The intraarticular and local administration of glucocorticosteroid preparations]. 2009 Feb 8 The author reports the use of short-acting and combined short + long-acting betamethasone injections for intraarticular and local treatments. In this paper the author describes his experiences with intraarticular and local treatments of 214 patients with 965 short-acting, and 416 patients with 2932 combined short + long-acting betamethasone preparations from 1978 to 2003. AIM: To describe the optimal application of intraarticular and local steroid therapy based on the author's experience and according to the literature data. METHOD: Patients were selected on the bases of rheumatological, laboratory and imaging investigations. The preparations were administered according to ARA guidelines. The results were evaluated based on patients' health status and symptoms, in addition to patients' and doctors' opinion. RESULTS: A combination of intraarticular short-acting + long-acting betamethasone injections resulted in patients being symptom-free (48.8%) or with significant improvement (37.5%), while local application led to a significant improvement (50%) or improvement (29%). Locally applied short-acting betamethasone resulted in symptom-free or significantly improved cases (40.6%), or ordinary improvement (40.3%). The short-acting + long-acting preparation was associated with mild side effects (62 cases), while the short-acting one had fewer mild side effects (10). The results are in agreement with the literature data, though in present author's case with a much fewer number of side effects. CONCLUSIONS: Intraarticular application of a combined short-acting + long acting agent is suggested exclusively in cases of visible and laboratory signs of inflammation that are limited to a few joints. In a treatment episode, not more than 3 injections may be permitted except in special cases. Initially, extraarticular management of cases is recommended using mainly short-acting preparations, except in protracted cases or when the application of short-acting steroids prove ineffective. Short-acting agents have little or short-term manifestations of corticosteroid toxicity. Taking such factors into consideration, treatment may be regarded as beneficial and safe. The aim of this publication is partly to influence practices in Hungarian surgeries.
19184473 Risk of cancer among rheumatoid arthritis patients in California. 2009 Aug OBJECTIVE: The objective of this retrospective cohort study was to evaluate cancer risk among rheumatoid arthritis (RA) patients in California. METHODS: The study cohort derived from statewide patient discharge records was followed via linkage with cancer registry data over the period 1991-2002. Age and sex adjusted standardized incidence ratios (SIRs) and 95% confidence intervals were calculated to compare observed to expected numbers of cancers based on age, race, and sex specific incidence rates in the California population. RESULTS: Among the 84,475 RA patients, who were observed for 405,540 person-years, 5,533 incident cancers were diagnosed during the observation interval. The risk of developing lymphohematopoietic cancer was significantly higher in the cohort for both sexes. Males had significantly higher risks of lung, liver, and esophageal cancer, but a lower risk of prostate cancer. Females were at significantly decreased risk for several cancers including breast, ovary, uterus, cervix, and melanoma, with the risk reduction ranging from 15 to 57% lower than the general population. Hispanics had increased risks of leukemia, vagina/vulva, lung, and liver cancers. CONCLUSION: Studies investigating the mechanisms that underlie the reported associations between RA and specific cancer types are needed.
20472599 A 78-joints ultrasonographic assessment is associated with clinical assessments and is hig 2010 Jul OBJECTIVES: To examine associations between ultrasonography (US) assessments (B-mode (BM) and power Doppler (PD)) of a large number of joints and traditional assessments of disease activity, and to examine the sensitivity to change of the US scores and clinical measures in patients with rheumatoid arthritis (RA). METHODS: Twenty patients with RA initiating adalimumab treatment were examined at baseline and after 1, 3, 6 and 12 months with US (BM and PD) using an Outcome Measures in Rheumatoid Arthritis Clinical Trial semiquantitative scoring (0-3) of 78 joints as well as assessment of clinical and laboratory variables with calculation of composite indexes. RESULTS: The US scores were associated with composite scores as well as clinical and laboratory variables (r=0.41-0.84, p<0.05-0.001 at 12-months' follow-up). Compared with clinical assessments, US detected higher numbers of inflamed joints. The US scores decreased after 1 and 3 months (p<0.005) and PD showed the highest percentage improvement. Both BM and PD had high standardised response means throughout the study (-0.83 to -1.27), of similar magnitude to composite indexes, but higher than the clinical and laboratory variables. CONCLUSIONS: The comprehensive US assessments were associated with clinical and laboratory variables of disease activity and were highly sensitive to change during treatment with biological agents.
19772799 Methotrexate information booklet study 2008. 2009 Jul INTRODUCTION: I n order to assess the value of using the methotrexate information booklet, we conducted a single blind prospective controlled trial of the patients attending two rheumatology services. METHODS: The active-arm (n=40) used the MTX information booklet for the patients' education and the control-arm (n=38) did not. Patients' interviews were conducted over a 6-month period using an MTX-questionnaire. RESULTS: The entire active-arm patients (100%) were taking folic-acid and 32 (80%) knew the reason why they were taking folic-acid vs. [30 (79%) and 10 (26%) in the control-arm]. In the active-arm 35 (88%) knew the reason for their monthly blood tests vs. 18 (47%) in the control-arm. The entire active-arm was aware of the need for contraception use and MTX-side effects vs. 23 (60%) and 15 (40%) in the control-arm respectively. CONCLUSIONS: The use of the MTX information booklet in our cohort improved their understanding of the treatment.
19019895 Formation of antibodies against infliximab and adalimumab strongly correlates with functio 2009 Nov BACKGROUND: Tumour necrosis factor alpha (TNFalpha) neutralising antibody constructs are increasingly being used to treat rheumatoid arthritis (RA). OBJECTIVE: To determine potential differences in clinical responses, soluble drug levels and antibody formation between patients with RA receiving infliximab and adalimumab. METHODS: 69 patients with RA fulfilling the 1987 American College of Rheumatology criteria and about to start treatment with infliximab or adalimumab, were enrolled consecutively. All patients had active disease (28-joint count Disease Activity Score >3.2). Infliximab was given intravenously at 3 mg/kg at baseline and after 2, 6 and 14 weeks. Adalimumab was administered as 40 mg biweekly subcutaneously. Concomitant drug treatment was monitored and continued at constant dosage during the study. All serum samples were tested for infliximab/adalimumab levels and anti-infliximab/anti-adalimumab antibodies. RESULTS: 35 patients received infliximab, 34 received adalimumab. At 6 months, 15 (43%), 6 (17%) and 14 (40%) of the infliximab-treated patients fulfilled the EULAR criteria for good, moderate and non-responders, respectively, whereas the corresponding figures for adalimumab-treated patients were 16 (47%), 8 (24%) and 10 (29%). Clinical responses correlated with the levels of S-infliximab/adalimumab and the formation of anti-infliximab/anti-adalimumab antibodies. CONCLUSION: The clinical response to two anti-TNFalpha biological agents closely follows the trough drug levels and the presence of antibodies directed against the drugs. Further studies that focus on the underlying pathways leading to antibody formation are warranted to predict immunogenicity of these expensive biological agents and treatment outcomes.
20024554 Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in 2011 Apr We investigated the effects of anti-IL-6 receptor antibody, tocilizumab (TCZ), on lipid metabolism. Nineteen patients with rheumatoid arthritis (RA), entered in clinical case-control study of SAMURAI trial at Sasebo Chuo Hospital, were examined. Nine patients received TCZ monotherapy at 8 mg/kg intravenously every 4 weeks (TCZ group) and 10 patients received conventional DMARDs (control group). Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), apolipoprotein (Apo) A-1, Apo A-2 and Apo B as well as disease activity score (DAS), C-reactive protein and serum amyloid A protein were examined at baseline and after 3 months of the treatment. IL-6 inversely was correlated with LDL, Apo A-1 and Apo A-2, and also tended to correlate with Apo B. In TCZ group, serum levels of TC, HDL, LDL, Apo A-1 and Apo A-2 were significantly increased after 3 months treatment with TCZ. There was no significant change in Apo B, the atherogenic index, and TC/HDL by the TCZ treatment. Changes in the DAS28-ESR negatively correlated with those in TC. In one patient, whose serum level of TCZ was not detected after 3 months of the treatment, the absence of the increment in serum levels of Apo A-1 and A-2 in the patient was remarkable. All of the markers did not change during 3 months in control group. These data may raise an important issue to evaluate the impact of these alternations in lipid metabolism for longer periods in RA patients treated with TCZ.
21211324 [Evaluation of MRI in the diagnosis of rheumatoid arthritis]. 2010 Nov 23 OBJECTIVE: to study the features of rheumatoid arthritis (RA) on MRI of hands and wrists and compare MRI with clinical manifestations and laboratory tests of RA. METHODS: a total of 25 patients fulfilling the 2009 ACR/EULAR RA criteria were enrolled. MRI and plain films of hands and wrists and clinical data of swollen joints, tender joints, visual scale (VAS) score, DAS28 score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF classification, anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) were obtained simultaneously. RESULTS: MRI revealed pathologic findings on the wrist and hand joints in all diagnosed RA patients. VAS had a positive correlation with bone marrow edema(r = 0.562, P = 0.003). Although the disease duration was less or more than 1 year, the difference of bone erosion had statistical significance between anti-CCP antibody-positive group and anti-CCP antibody negative group (all P = 0.000). The serum concentration of RF-IgA had a positive correlation with bone marrow edema (r = 0.561, P = 0.041). The synovitis score of MRI of RA was higher in the RF-IgG positive group than that in the RF-IgG negative group (P = 0.035). There was significant difference in MRI synovitis between the RF-IgG or RF-IgM positive and negative groups of patients with a disease course of under 1 year (P = 0.015, P = 0.007). The serum CRP level had a positive correlation with arthroderma (r = 0.457, P = 0.022). CONCLUSION: MRI is proved to be a valuable examination for an early diagnosis and assessment of RA.
20545470 Positive serum antigliadin antibodies without celiac disease in the elderly population: do 2010 Oct OBJECTIVE: Antigliadin antibodies (AGA) show good sensitivity but low specificity for celiac disease and can also be found in healthy individuals. However, data suggest that AGA positivity might be related to distinct disease entities such as allergy and gluten ataxia. Our aim here is to explore the clinical relevance of positive AGA in the elderly population. MATERIAL AND METHODS: Serum IgA- and IgG-class AGA and IgA-class tissue transglutaminase antibodies (tTGA) were determined in 2815 individuals aged 52-74 years. Equal numbers of AGA- and tTGA-negative participants of similar age and gender, but without known celiac disease, were randomly selected as controls. Information on clinical history was obtained from hospital records in all groups. RESULTS: Altogether 381 persons were positive for IgA/IgG-class AGA; 38 (14%) of them were also positive for tTGA. Out of the biopsied subjects, 34 (100%) in the AGA+ tTGA+ group and five (9%) in AGA+ tTGA- group had celiac disease. Rheumatoid arthritis and depression were found significantly more often in AGA-positives than controls. The significance remained even when tTGA-positive and known celiac disease cases were excluded. No statistical differences were found in the occurrence of neurological diseases, diabetes, allergic and cardiovascular diseases or malignancies. CONCLUSIONS: Although AGA positivity is of clinical relevance only in a subset of elderly people, it seems to be related to rheumatoid arthritis and depression, both conditions linked to celiac disease. Further studies are needed to reveal the mechanisms underlying this. The poor specificity of AGA for celiac disease was here once more in evidence.
20192991 Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of r 2010 Jan Rheumatoid arthritis (RA) is now clearly a true autoimmune disease with accumulating evidence of pathogenic disease-specific autoimmunity to citrullinated proteins. Citrullination, also termed deimination, is a modification of arginine side chains catalyzed by peptidylarginine deiminase (PAD) enzymes. This post-translational modification has the potential to alter the structure, antigenicity, and function of proteins. In RA, antibodies to cyclic citrullinated peptides are now well established for clinical diagnosis, though we argue that the identification of specific citrullinated antigens, as whole proteins, is necessary for exploring pathogenic mechanisms. Four citrullinated antigens, fibrinogen, vimentin, collagen type II, and alpha-enolase, are now well established, with others awaiting further characterization. All four proteins are expressed in the joint, and there is evidence that antibodies to citrullinated fibrinogen and collagen type II mediate inflammation by the formation of immune complexes, both in humans and animal models. Antibodies to citrullinated proteins are associated with HLA 'shared epitope' alleles, and autoimmunity to at least one antigenic sequence, the CEP-1 peptide from citrullinated alpha-enolase (KIHAcitEIFDScitGNPTVE), shows a specific association with HLA-DRB1*0401, *0404, 620W PTPN22, and smoking. Periodontitis, in which Porphyromonas gingivalis is a major pathogenic bacterium, has been linked to RA in epidemiological studies and also shares similar gene/environment associations. This is also the only bacterium identified that expresses endogenous citrullinated proteins and its own bacterial PAD enzyme, though the precise molecular mechanisms of bacterial citrullination have yet to be explored. Thus, both smoking and Porphyromonas gingivalis are attractive etiological agents for further investigation into the gene/environment/autoimmunity triad of RA.
19816690 Terminal monosaccharide screening of synovial immunoglobulins G and A for the early detect 2010 Aug The expressions of some terminal glycotopes of synovial immunoglobulins G, A, and M were analysed in relation to rheumatoid arthritis (RA) progression defined according to early and advanced radiological changes in patients' hands. The relative amounts of terminal monosaccharides were determined by lectin-immunoblotting of immunoglobulin preparations using appropriate lectins able to recognize alpha2,6-linked (Sambucus nigra agglutinin) and alpha2,3-linked (Maackia amurensis agglutinin) sialic acid, galactose (Ricinus communis agglutinin I), N-acetylglucosamine (Griffonia simplicifolia agglutinin II) as well as alpha1,6-linked (Aleuria aurantia lectin), alpha1,3-linked (Lotus tetragonolobus agglutinin), and alpha1,2-linked (Ulex europaeus agglutinin) fucose. The results indicate differences between early and advanced RA stages in the terminal sugar exposition of synovial IgG and IgA, but not IgM. The galactose-deficient glycotope with exposed N-acetylglucosamine of the synovial 33.1-kDa IgG fragment appeared exclusively in the early stage of RA. In contrast, this glycotope of intact synovial IgG and IgA was present in both groups, although with higher proportions in advanced RA. The proportions of the sialyl and fucosyl determinants of intact synovial A and G immunoglobulins were clearly lower in the early RA group than in the advanced. The analysis of terminal oligosaccharide exposition in IgG, IgG fragments, and IgA present in the synovial fluid of RA patients might be applicable as a stage-specific marker in the diagnosis and therapy of RA patients.
19395456 Autoantibodies against galectin-8: their specificity, association with lymphopenia in syst 2009 May The role of autoantibodies in the pathogenesis of systemic lupus erythematosus (SLE) has not been completely defined. From more than a hundred autoantibodies described in SLE, relatively few have been associated with clinical manifestations. The glycan-binding proteins of the galectin family can modulate the immune system. Anti-galectin autoantibodies thus could have functional and/or pathogenic implications in inflammatory processes and autoimmunity. We previously reported function-blocking autoantibodies against galectin-8 (Gal-8) in SLE. Here we tested these autoantibodies against a series of other human galectins and demonstrated their specificity for Gal-8, being detectable in 23% of 78 SLE patients. Remarkably, they associated with lymphopenia (50% of 18 anti-Gal-8-positive versus 18% of 60 anti-Gal-8-negative cases, Fisher's Exact test two-tailed: P < 0.012). Lymphopenia is a common clinical manifestation in SLE, yet of unknown mechanism. In addition, six of eight patients with both lymphopenia and malar rash had anti-Gal-8 in their sera. Occurrence of these autoantibodies was not confined to SLE as we also found them in sera of patients with rheumatoid arthritis (16%) and septicemia (20%). This study thus establishes occurrence of specific anti-Gal-8 autoantibodies in autoimmune rheumatic diseases and in acute inflammation, with an apparent association to a clinical subset in SLE.
19593497 [Assessment of nutritional status in a Mexican population of adult patients with rheumatoi 2009 Mar BACKGROUND: Rheumatoid arthritis (RA) represents a life-long chronic inflammatory process frequently associated to potential multiorganic complications. Cardiovascular diseases and nutritional alterations are increased in AR populations and represent potential factors that alter negatively the disease course and prognosis. PURPOSE: To evaluate nutritional status from a Mexican AR population, including body composition, anthropometrics and dietary patterns. MATERIAL AND METHODS: There were included 100 RA outpatients from a regional rheumatic centre located in San Luis Potosi México. Nutritional assessment included anthropometric evaluation, bioelectrical impedance analysis (BIA) and dietary patterns evaluation. RESULTS: 100 RA out-patients were included. Mean age was 47.6 +/- 13.3 years, with a mean disease course of 10.18 +/- 9.02. 79% of patients were in RA functional class II and 21% in class III. Average body mass index 26.8 +/- 4.4 kg/m2 According to body mass index categories, 65% patients were within the range of overweight and obesity and 2% of patients were undernourished. Mean waist circumference 86.7 +/- 11.1 cm, 34% of patients showed waist circumference values over the limits established for the definition of metabolic syndrome. Lean body mass was diminished in 48% patients. Body fat mass estimated by anthropometry and BIA was increased in 94 patients (94%). DIETARY PARAMETERS: Mean energy intake was 26.4 +/- 8.2 kcal/kg. There was qualitative nutritional inadequacy in 90 patients (90%). Protein intake was optimal in all the patients. CONCLUSION: Nutritional alterations are highly prevalent in Mexican RA population; our study showed freefat mass depletion, low caloric intake, dietary inadequate parameters and fat mass increments as the more prevalent findings. Nutritional assessment and nutritional strategies are recommended as potential measures to improve RA clinical course and prognosis.
19884269 Citrulline dependence of anti-cyclic citrullinated peptide antibodies in systemic lupus er 2009 Dec OBJECTIVE: Anti-cyclic citrullinated peptide (CCP) antibodies are a serological marker for rheumatoid arthritis (RA); up to 10%-15% of patients with systemic lupus erythematosus (SLE) are also positive. While anti-CCP in RA is citrulline-dependent, anti-CCP in some other diseases is citrulline-independent and reacts with both CCP and the unmodified (arginine-containing) cyclic arginine peptide (CAP). We investigated the citrulline dependence of anti-CCP and its significance in the arthritis of SLE. METHODS: IgG anti-CCP was compared by ELISA to anti-CAP in sera from patients with SLE (n = 335) and RA (n = 47) and healthy controls (n = 35). SLE patients were divided into 5 groups based on their joint involvement: subset I: deforming/erosive arthritis (n = 20); II: arthritis fulfilling (or likely fulfilling) American College of Rheumatology criteria for RA but without erosions (n = 18); III: joint swelling but not fulfilling RA criteria (n = 39); IV: arthritis without documented joint swelling (n = 194); and V: no arthritis (n = 58). RESULTS: Anti-CCP (> 1.7 units) was found in 68% (32/47) of patients with RA and 17% (55/329) of those with SLE. It was more common in SLE patients with deforming/erosive arthritis (38%). High anti-CCP (> 10 units) was found in RA (26%) and deforming/erosive SLE (12%). High anti-CCP/CAP ratios (> 2, indicating a selectivity to CCP) were found in 91% of anti-CCP-positive RA and 50% of anti-CCP-positive SLE patients with deforming/erosive arthritis. Patients from subset II did not have high anti-CCP/CAP. CONCLUSION: Citrulline dependence or high levels (> 10) of anti-CCP were common in SLE patients with deforming/erosive arthritis, while most anti-CCP in SLE patients was citrulline-independent. This may be useful in identifying a subset of SLE patients with high risk for development of deforming/erosive arthritis.
20354747 Antibodies against oxidized low-density lipoprotein are associated with subclinical athero 2010 Nov Rheumatoid arthritis (RA) patients have increased mortality largely as a result of cardiovascular diseases (CVD) that cannot be explained by traditional risk factors, suggesting that systemic inflammation may accelerate atherosclerosis. We investigated the presence of subclinical atherosclerosis in early RA (<12 months) and the possible association of RA-related risk factors. Forty patients with early RA and 40 controls matched for age, sex, and traditional risk factors for CVD were selected. Carotid US examination, assay of lipogram, C-reactive protein (CRP), and oxidized low-density lipoprotein antibodies (OxLDL-ab) were done. RA patients had significantly higher carotid intima-media thickness (cIMT) values and more plaque than the control (P<0.001 and P=0.0122, respectively). CRP and OxLDL-ab were significantly higher in RA patients than controls. Traditional risk factors and RA-related risk factors (disease duration, DAS-28, duration of treatment with steroids, erythrocyte sedimentation rate, and CRP) as well as OxLDL and cIMT were significantly higher in RA with plaques compared to those without plaques. Regression analysis identified the age of patients, CRP, and OxLDL-ab as an independent risk factor associated with the presence of atherosclerosis. CONCLUSION: there is increased prevalence of carotid plaques in patients with recent-onset RA compared to matched controls. The accelerated atherosclerosis is predicted by age, CRP, and oxLDL-ab. The association of plaques with elevated CRP and OxLDL-ab support the hypothesis that chronic systemic autoimmune inflammatory process is probably a driving force for premature atherosclerosis.