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

ID PMID Title PublicationDate abstract
17195206 Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme and rheuma 2007 Jan OBJECTIVE: Analyses of families with rheumatoid arthritis (RA) have suggested the presence of a putative susceptibility locus on chromosome 14q21-23. This large population-based genetic association study was undertaken to examine this region. METHODS: A 2-stage case-control association study of 950 unrelated Japanese patients with RA and 950 healthy controls was performed using >400 gene-based common single-nucleotide polymorphisms (SNPs). RESULTS: Multiple SNPs in the PRKCH gene encoding the eta isozyme of protein kinase C (PKCeta) showed significant single-locus disease associations, the most significant being SNP c.427+8134C>T (odds ratio 0.72, 95% confidence interval 0.62-0.83, P = 5.9 x 10(-5)). Each RA-associated SNP was consistently mapped to 3 distinct regions of strong linkage disequilibrium (i.e., linkage disequilibrium or haplotype blocks) in the PRKCH gene locus, suggesting that multiple causal variants influence disease susceptibility. Significant SNPs included a novel common missense polymorphism of the PRKCH gene, V374I (rs2230500), which lies within the ATP-binding site that is highly conserved among PKC superfamily members. In circulating lymphocytes, PRKCH messenger RNA was expressed at higher levels in resting T cells (CD4(+) or CD8(+)) than in B cells (CD19(+)) or monocytes (CD14(+)) and was significantly down-regulated through immune responses. CONCLUSION: Our results provide evidence of the involvement of PRKCH as a susceptibility gene for RA in the Japanese population. Dysregulation of PKCeta signal transduction pathway(s) may confer increased risk of RA through aberrant T cell-mediated autoimmune responses.
19024003 Experimental and clinical study of the effect of artrofoon on proinflammatory cytokine pro 2008 Jan The effect of Artrofoon on the production of proinflammatory cytokines was evaluated in experiments on mice with collagen-induced arthritis and in a clinical study on patients with rheumatoid arthritis. Artrofoon produced an antiinflammatory effect on animals with collagen-induced arthritis and reduced clinical signs of inflammation in patients with rheumatoid arthritis. These changes were accompanied by a significant decrease in the production of tumor necrosis factor-alpha and interleukin-1beta.
18050188 General and specific factors associated with severity of cognitive impairment in systemic 2007 Dec 15 OBJECTIVE: To determine factors affecting the severity of cognitive impairment in systemic lupus erythematosus (SLE) and to analyze its anatomic location. METHODS: Fifteen cognitive functions grouped into 8 domains were evaluated in 52 patients with SLE and 20 with rheumatoid arthritis. Patients were classified according to severity of impairment as normal, mild, or moderate/severe. Multivariate analysis was performed to identify the main factors affecting severity of cognitive deficits. The most likely anatomic site of damage according to neuropsychological performance was compared with the lesion's location on magnetic resonance imaging (MRI). RESULTS: In SLE patients, a stepwise regression analysis showed that the number of impaired functions (dependent variable) was associated with antiphospholipid antibody positivity (aPL+; P = 0.04), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI; P = 0.001), hypertension (P = 0.032), and was inversely related to educational level (P = 0.021). Including MRI, the number of impaired functions was associated with severity of MRI (P < 0.001), the SDI (P = 0.013), and the presence of Raynaud's phenomenon (P = 0.04). The contemporary presence of aPL+ and Raynaud's phenomenon resulted in a higher probability to develop moderate/severe cognitive deficits (P = 0.015). Two logistic multiple regression analyses identified hypertension (P < 0.05), the SDI (P < 0.01), and moderate/severe MRI findings as main predictors of moderate/severe impairment (dependent variable). The damage site hypothesized through neuropsychological testing corresponded with MRI findings in 71.7% of SLE patients K = 0.42, P = 0.005). CONCLUSION: Hypertension, aPL+, accumulated damage, and MRI lesions are the main factors affecting severity of cognitive impairment in SLE. The hypothesized sites of central nervous system involvement according to neuropsychological testing correlated with MRI findings in most patients.
17951675 In vitro matrigel fibroblast invasion assay. 2007 Rheumatoid arthritis is characterized by inflammation of the joints and degradation and invasion by fibroblast-like synoviocytes (FLS) of the cartilage. To assess the invasiveness of FLS an in vitro invasion assay was developed. In this invasion assay the FLS grow through an artificial matrix composed mainly of collagen IV. First, the walls of transwells are coated with paraffin to avoid meniscus formation. Subsequently, the bottoms of the transwells (on top of the membrane) are coated with a thin layer of matrigel. On top of this matrigel fibroblast-like synoviocytes are seeded at a density of 100,000 cells per milliliter. The cells are cultured in serum free medium in the inner compartment inside the transwell. To the outer compartment outside the transwell IMDM with 10% fetal calf serum and 10% NHS is added. The cells are incubated for 3 d at 37 degrees C and 5% CO2. After 3 d the cells are fixed with 2% glutaraldehyde in phosphate buffered saline and stained with 1% crystal violet in water. The matrix on the inside of the transwells and the cells that have not grown through the matrix and the membrane are removed. The cells that have grown through the matrix and through the membrane under the transwell can be visualized by light microscopy and counted.
18246353 Application of three-dimensional computed tomography for the rheumatoid wrist. 2008 Jun Recent technical advances in computed tomography (CT) and the introduction of three-dimensional (3D) image reconstruction through computer systems make distinct visualization of tiny defects in the hand and wrist a feasible task. Three wrists from three patients -- two of whom are patients with rheumatoid arthritis and one with osteoarthritis -- were evaluated by 3D CT. Images were obtained with a multidetector-row CT scanner. Bony wrist structures including erosions were observed in the patients with arthritis by means of 3D CT. 3D CT could clearly visualize bone-erosive lesions. It also revealed various interesting stereoscopic views of bony structures unattainable with conventional radiographic studies. 3D CT may serve to be interesting in future imaging studies in the rheumatology field.
16740333 Fatigue and rheumatoid arthritis. 2006 Jul Fatigue is a common complaint among patients with rheumatoid arthritis (RA) and is regarded as an extra-articular symptom of the disease. Little attention has been paid by health professional teams to the multidimensional nature of RA-related fatigue and its wide-ranging consequences for quality of life. Unlike normal tiredness, fatigue is chronic, typically not related to overexertion and poorly relieved by rest. The prevalence is high and several RA-related components have been reported as predictors of fatigue. RA-related fatigue appeared to be strongly associated with psychosocial factors. Fatigue assessment and management are complex because psychological and physiological factors may be involved. Several instruments that have been used in RA to assess fatigue. They have involved a self-reporting format. Some are brief, quantitative and symptom-focused questionnaires. Others provide a multidimensional assessment. DMARD therapy, especially anti-TNF decreased disease activity and alleviates fatigue. An additional direct effect is hypothetical. The non-pharmacological management includes behavioral therapy or self-management courses and physical exercise. Finally, the importance and relevance of fatigue as an outcome measure is becoming highlighted by research groups and should lead to improved management of fatigue in usual medical practice.
18722728 Computer-assisted quantification of interstitial lung disease associated with rheumatoid a 2009 Nov PURPOSE: To validate a threshold-based prototype software application (MeVis PULMO 3D) for quantification of chronic interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) using variable threshold settings for segmentation of diseased lung areas. METHODS: Twenty-two patients with rheumatoid arthritis were included and underwent thin-section CT (4x1.25mm collimation). CT scans were assessed by two observers for extent of ILD (EoILD), and twice by MeVis PULMO 3D for each protocol. MeVis PULMO 3D used four segmentation threshold (ST) settings (ST=-740, -780, -800 and -840HU). Pulmonary function tests were obtained in all patients. Statistical evaluation used 95% limits of agreement (LoA) and linear regression analysis. RESULTS: There was total concordance between the software measurements. Interobserver agreement was good (LoA=-28.36 to 17.58%). EoILD by readers correlated strongly with DL(CO) (r=-0.702, p<0.0001) and moderately with FVC (r=-0.523, p=0.018). There was close correlation between readers and MeVis PULMO 3D with best results for ST <780HU (EoILD vs. MeVis PULMO 3D: r=0.650 for ST=-800 and -840HU, respectively; p=0.002). MeVis PULMO 3D correlated best with DL(CO) at ST of -800HU (r=-0.44, -0.49, -0.58 and -0.57 for ST=-740, -780, -800 and -840, respectively; p=0.007-0.05) and moderately with FVC (r=-0.44, -0.51, -0.59 and -0.45 for ST=-740, -780, -800 and -840), respectively; p=0.007-0.05). CONCLUSION: The MeVis PULMO 3D system used holds promise to become a valuable instrument for quantification of chronic ILD in patients with RA when using the threshold value of -800HU, with evidence of the closest correlations, both with human observers and physiologic impairment.
17977580 Cancer in rheumatoid arthritis: occurrence, mortality, and associated factors in a South E 2008 Jun OBJECTIVES: To estimate the prevalence, incidence, mortality, and predictors of cancer in patients with rheumatoid arthritis (RA). METHODS: We compared the incidence of cancer and the mortality by cancer in a cohort of 789 randomly selected RA patients (1999-2005) with the expected ones in the general population. We estimated standardized incidence ratios (SIR) and standardized mortality ratios (SMR) by indirect age and sex standardization. Additionally, we analyzed by generalized linear models the association of various predictors with cancer incidence, obtaining incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: The SIR of cancer in RA is 1.23 (95% CI: 0.78-1.85). By cancer type, there is an increased risk of leukemia, non-Hodgkin's lymphoma, and lung cancer in RA compared with the general population of the same sex and age. The SMR of cancer is 1.0 (95% CI: 0.53-1.7). By cancer type, RA patients with lung or kidney cancer have higher mortality than expected. Being male, elderly, with longstanding disease, and having used any cytotoxic drugs apart from methotrexate are confirmed as predictive factors for cancer. Additional independent predictors are increases in blood leukocyte counts (IRR per 3000 u/mm3 increase: 1.88 (95% CI: 1.6 -2.1)) and decreases in serum hemoglobin (IRR per 2 g/l decrease: 1.88 (95% CI: 1.19 -2.94)). CONCLUSIONS: The overall incidence and mortality of cancer in RA is not greater than the expected, although there is an increased risk of hematopoietic and lung cancers in RA patients compared with the general population. Hemoglobin and leukocyte counts may help to identify RA patients at risk for cancer.
16625342 The relation between joint erosion and generalized osteoporosis and disease activity in pa 2006 Aug The aim of this study is to investigate the correlation between joint erosion and osteoporosis in patients with rheumatoid arthritis (RA). Fifty-one patients with RA were included for the study. Hand radiograms of all patients were evaluated by the Larsen modified Sharp and carpometacarpal ratio methods. Bone mineral density (BMD) measurements were performed at the femur, lumbar, and forearm regions. Disease activity was assessed clinically by the health assessment questionnaire (HAQ), visual analog scale, erythrocyte sedimentation rate, C-reactive protein (CRP), and the rheumatoid factor (RF). There was no statistically significant difference in terms of the BMD values at L1-4 between the patients with RA and the control group. The BMD measurements at the right forearm and the right hip were statistically significantly lower in the patient group. For radiological scoring, hand radiograms were evaluated by three different methods. There was a significant correlation between the duration of disease and the radiological evaluation methods. HAQ scores, Larsen and Sharp methods 1/3 distal and mid-distal (MID), and BMD measurements of the forearm were correlated. Moreover, 1/3 distal, MID, and ultra-distal BMD showed significant correlations with CRP levels. Radiogram continues to have an important role in determining and following-up the joint erosion seen in patients with RA. However, we believe that as establishing periarticular osteoporosis in the early term by performing BMD measurements on the forearm is correlated with disease activity, it may be useful in the early diagnosis of RA and its objective results will be efficient in predicting the progression of disease.
17526444 [Early arthritis]. 2007 Jun 3 Identifying the cause of polyarthritis can be difficult because of the extensive differential diagnosis. A thorough history and a complete physical examination are essential. Clinical factors such as disease chronology, inflammation, distribution, extra-articular manifestations, disease course are helpful in narrowing the possible causes. Many classic laboratory tests are nonspecific but these, together with specific tests and radiographs, may provide more useful diagnostic clues. Early arthritis may progress into established rheumatoid arthritis or another definite arthropathy, may resolve spontaneously, or may remain undifferentiated. To achieve better diagnosis and outcome in arthritis, it is important to recognize inflammatory arthritis first, then to establish the definitive diagnosis of arthritis and finally to estimate the risk of developing persistent or/and erosive irreversible arthritis to propose an optimal therapeutic strategy (within 3 months) in order to avoid joint destructions and function-loss and to provide a good quality of life.
19210876 MEFV mutations in Japanese rheumatoid arthritis patients. 2008 Nov OBJECTIVE: Familiar Mediterranean Fever (FMF) is common among Mediterranean populations, while other populations are rarely affected. The aim of this study was to assess the involvement of MEFV gene mutations among Japanese rheumatoid arthritis patients with or without amyloid A (AA) amyloidosis. METHODS: The frequency of the MEFV mutations, which were identified in Japanese FMF patients, was determined in 126 Japanese RA patients and 76 Japanese healthy subjects. RESULTS: The M694I mutation was not observed among RA patients and healthy subjects. Allele frequency of R408Q, P369S, E148Q, L110P mutations account respectively for 3.3%, 3.9%, 23.7%, 9.2% in healthy subjects and 5.6%, 6.7%, 24.2%, 9.5% in RA patients. The overall mutation rate was comparable between the RA patients and healthy subjects, as well as between the RA patients with and without amyloidosis. CONCLUSION: This study shows the high prevalence of mutations of the MEFV genes in Japanese RA patients. However, our data suggest that the MEFV gene mutations may not be a genetic factor affecting the susceptibility of RA or the development of amyloidosis in a Japanese population.
18568393 Parthenolide inhibits proliferation of fibroblast-like synoviocytes in vitro. 2008 Aug Parthenolide is a bioactive constituent of an aromatic herb Feverfew (Tanacetum parthenium). It has been found that both parthenolide and extract of feverfew have anti-inflammatory and antinociceptive properties. Moreover, they demonstrate antiproliferative activities on different human tumour cells. The massive hyperplasia of synovial fibroblasts is the one of the most striking features of rheumatoid arthritis. It is not known whether this is due to the proliferation of synovial fibroblasts or to defective apoptosis. We investigated the effect of parthenolide on the proliferation of rabbit synoviocytes cell line HIG-82, rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and human skin fibroblasts (HSF) in vitro. Cell proliferation was assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 5'-bromo-2'-deoxy-uridine methods. Parthenolide inhibited proliferation of HIG-82 and human RA-FLS. The proliferation of HSF was inhibited less effectively. The antiproliferative potential of parthenolide was demonstrated.
16758915 [The peculiarities of pulmonary pathology in rheumatoid arthritis]. 2006 The review covers the problems of terminology, pathogenesis, morphology, clinical manifestations, and diagnostics of pulmonary pathology in patients with rheumatoid arthritis (RA). The main variants of pulmonary and pleural changes in RA are presented. The article covers possibilities provided by modern technologies, which make it possible to widen and objective diagnostic methods, including those directed towards revealing specific changes in respiratory organs in RA patients. The authors give preference to non-invasive radiodiagnostic methods, among which the leading role is played by high-resolution computed tomography due to its high information value in the imaging of pulmonary pathology, compared with conventional chest radiograms. The article also covers the issue of the complex application of non-invasive methods, such as functional (including methods of diffusing lung capacity evaluation), radiological and radionuclid ones, and invasive methods including fibrobronchoscopy, bronchoalveolar lavage, and lung biopsy, in diagnostics of interstitial pulmonary lesion, especially its subclinical variants.
18625641 Adalimumab-induced lupus erythematosus. 2008 Jul Adalimumab, an anti-tumour necrosis factor agent, especially used in the treatment of rheumatoid arthritis, has a good safety profile. One of the most common side-effects of adalimumab is the development of autoantibodies. Despite the induction of autoantibodies, the clinical presentation of immune-mediated complications upon adalimumab therapy, including a lupus-like syndrome, is very rare. We have recently evaluated a new case of adalimumab-induced lupus erythematosus.
17437662 Monitoring cartilage turnover. 2007 Apr In arthritic diseases, the stability of the extracellular matrix of articular cartilage is compromised by extensive proteolytic breakdown associated with alterations of synthesis of the proteins of the tissue leading to cartilage loss. This article reviews developments in assays of biochemical markers of cartilage matrix turnover and studies investigating their use. Because type II collagen and aggrecan are the most abundant proteins of the cartilage matrix, current biochemical markers are based mainly on immunologic reagents detecting their synthesis and degradation. Clinical studies indicate that some markers of type II collagen may be useful to predict disease progression in osteoarthritis and rheumatoid arthritis. Conversely, major achievements have been made in the development of immunoassays detecting the various fragments of aggrecan released by matrix metalloproteases or aggrecanases, but their use has been limited mostly to investigating cartilage turnover in ex vivo experiments. Because of the complexity of the mechanisms involved in arthritic joint damage, only a combination of different biochemical markers reflecting the various aspects of synthesis and degradation of matrix molecules will likely provide efficient cartilage turnover monitoring.
18512711 Abnormal body composition phenotypes in older rheumatoid arthritis patients: association w 2008 Jun 15 OBJECTIVE: To compare measures of body fat and lean mass and the prevalence of abnormal body composition phenotypes (sarcopenia, overfat, and sarcopenic obesity) in men and women with rheumatoid arthritis (RA) versus matched controls, and to explore the disease-related predictors of abnormal body composition in patients with RA. METHODS: A total of 189 men and women with RA and 189 age-, sex-, and race-matched non-RA controls underwent dual-energy x-ray absorptiometry for measurement of total and regional body fat and lean mass. Continuous and categorical measures of body composition were compared between RA and control subjects by sex and according to categories of body mass index (BMI). Within the group of RA patients, demographic, lifestyle, and RA disease and treatment characteristics were compared for RA patients with healthy body composition versus those with abnormal body composition phenotypes. RESULTS: Compared with non-RA controls, RA status was significantly associated with greater odds of sarcopenia, overfat, and sarcopenic obesity in women, but not in men. Relative differences in body composition phenotypes between RA and control subjects were greatest for patients in the normal weight BMI category (<25 kg/m(2)). Among RA characteristics, increasing joint deformity, self-reported disability scores, C-reactive protein levels, rheumatoid factor seropositivity, and a lack of current treatment with disease-modifying antirheumatic drugs were significantly associated with abnormal body composition. CONCLUSION: Abnormal body composition phenotypes are overrepresented in patients with RA, particularly in those in the normal weight BMI range. RA-associated disease and treatment characteristics contribute to this increase in abnormal body composition.
17568917 [Evaluation of body composition and bone mineral density in women with rheumatoid arthriti 2007 Mar Decrease of bone mass and changes in body composition are common in patients with rheumatoid arthritis (RA) especially in users of glucocorticoids. OBJECTIVE: To evaluate the bone mineral density (BMD) and its correlation to factors of body composition in women with RA. METHODS: BMD and body composition (total and regional) were measured by DXA in 83 patients with rheumatoid arthritis. In addition, a lateral dorsal and lumbar spine x-ray was carried out as well as laboratory tests (rheumatoid factor, inflammatory exams). Information about activity of disease, functional class, physical activity and alimentary data were collected using specific questionnaires. RESULTS: The prevalence of osteoporosis in menopausal patients was 21.4% (12 patients), of osteopenia 46.4% (26 patients) while 32.1% were normal (18 patients). Osteoporosis was similar in the lumbar spine and the femoral neck. More than half the patients showed low BMD in the lumbar and/or femoral neck. Non Caucasian and premenopausal women had the highest values of BMD averages. The cumulative dose of glucocorticoids for the last two years was a negative determinant of total lean mass. Age had a negative effect on BMD and body composition measurements. BMI showed a positive effect in all BC variables. Functional classes 3 and 4 had a negative effect only on the BMD total. Physical activity had a positive effect on BMD of the total femur. Duration of RA had a negative effect on BMD in the lumbar spine. The GC dose used in the last 3 months showed a negative effect on the total lean mass (MMT) and doses of the last 2 years had a positive effect on the total fat percentage (TFP). Finally, the estrogen exposure time (EET) indicated a positive effect on total fat percentage (TFP). CONCLUSION: A decreased BMD found in 67.8% of patients suggests a better approach to prevention and treatment as from diagnosis of the disease. Age and non Caucasian race were negative factors for BMD values, while BMI was a positive factor for all BMD and body composition variables. The disease (RA) also had a negative influence on BMD of these women and use of GC produced changes in body composition, reducing the lean mass and increasing the fat percentage. Despite lack of evidence of a harmful direct action of oral corticoids on BMD, their use should be avoided. Therefore, preserving lean mass and enhancing BMD is important for these patients, in order to decrease fractures and falls.
18793006 RAPID3 (Routine Assessment of Patient Index Data 3), a rheumatoid arthritis index without 2008 Nov OBJECTIVE: To compare 4 categories (high, moderate, and low severity, and near-remission) of RAPID3 (Routine Assessment of Patient Index Data 3), an index without formal joint counts, which is scored in < 10 seconds to 4 categories of the Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI) in patients with rheumatoid arthritis (RA). METHODS: All patients complete a Multidimensional Health Assessment Questionnaire (MDHAQ) at each visit. A physician/assessor 28-joint count and erythrocyte sedimentation rate (ESR) were completed in 285 patients with RA in usual care by 3 rheumatologists to score DAS28, CDAI, and RAPID3. RAPID3 includes the 3 MDHAQ patient self-report RA Core Data Set measures for physical function, pain, and patient global estimate. Proposed RAPID3 (range 0-10) severity categories of high (> 4), moderate (2.01-4), low (1.01-2), and near-remission (< or = 1) were compared to DAS (0-10) activity categories of high (> 5.1), moderate (3.21-5.1), low (2.61-3.2), and remission (< or = 2.6), and CDAI (0-76) categories of > 22, 10.1-22.0, 2.9-10.0, and < or = 2.8. Additional RAPID scores, which add to RAPID3 a physician/assessor or patient self-report joint count and/or assessor global estimate, were also analyzed. Statistical significance was analyzed using Spearman correlations, cross-tabulations, and kappa statistics. RESULTS: All RAPID scores were correlated significantly with DAS28 and CDAI (rho > 0.65, p < 0.001). Overall, 78%-84% of patients who met DAS28 or CDAI moderate/high activity criteria met similar RAPID severity criteria, and 68%-77% who met DAS28 or CDAI remission/low activity criteria also met similar RAPID criteria. RAPID3 was as informative as other indices. CONCLUSION: RAPID3 provides a feasible, informative quantitative index for busy clinical settings.
18507823 Patients with rheumatoid arthritis have an altered circulatory aggrecan profile. 2008 May 28 BACKGROUND: Rheumatoid arthritis (RA) is a chronic auto-immune disease with extensive articular cartilage destruction. Aggrecan depletion, mediated by aggrecanases is one of the first signs of early cartilage erosion. We investigated, whether measurement of aggrecan and fragments thereof in serum, could be used as biomarkers for joint-disease in RA patients and furthermore characterized the fragments found in the circulation. METHODS: The study consisted of 38 patients, 12 males (62.2 +/- 16.0 years) and 26 females (59.8 +/- 20.7 years) diagnosed with RA: 41.5 +/- 27.5 mm/h erythrocyte sedimentation rate (ESR), 38.4 +/- 34.7 mg/ml C-reactive protein (CRP) and 4.8 +/- 1.7 disease activity score (DAS) and 108 healthy age-matched controls. Aggrecan levels were measured using two immunoassays, i.e. the (374)ARGSVI-G2 sandwich ELISA measuring aggrecanase-mediated aggrecan degradation and the G1/G2 sandwich assay, detecting aggrecan molecules containing G1 and/or G2 (total aggrecan) We further characterized serum samples by western blots, by using monoclonal antibodies F-78, binding to G1 and G2, or by BC-3, detecting the aggrecanase-generated N-terminal 374ARGSVI neo-epitope. RESULTS: Total aggrecan levels in RA patients were significantly decreased from 824.8 +/- 31 ng/ml in healthy controls to 570.5 +/- 30 ng/ml (31% decrease, P < 0.0001), as measured by the G1/G2 ELISA. Western blot analysis with F-78 showed one strong band at 10 kDa, and weaker bands at 25 and 45 kDa in both healthy controls and RA patients. In contrast, staining for aggrecanase-activity revealed only one strong band in RA patients of 45 kDa. CONCLUSION: This is the first study, which characterizes different aggrecan fragments in human serum. The data strongly suggests that total aggrecan levels, i.e. aggrecan molecules containing G1 and/or G2 are lower in RA patients, and that RA patients have at least one specific subpopulation of aggrecan fragments, namely aggrecanse generated 374ARGSVI fragments. Further clinical studies are needed to investigate the potential of G1/G2 as a structure-related biochemical marker in destructive joint-diseases.
17181921 Regulation of serum chemokines following infliximab therapy in patients with rheumatoid ar 2006 Sep OBJECTIVE: We studied the effects of the multiple infusions of infliximab, a chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody, on the serum chemokines levels in patients with active rheumatoid arthritis (RA). METHODS: RA patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter with the same dose. All patients continued treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at weeks 0, 2, 6, 14, 38, prior to infusion, and additionally at week 62. RESULTS: Initial infusion of infliximab caused reduction in serum IL-8, RANTES and MCP-1 (in all cases p < 0.001) levels. Subsequent infliximab administrations also significantly decreased serum chemokines levels, but was less effective. Prior to the first infliximab infusion serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) or CRP levels, number of swollen joints and disease activity score (DAS). Following next drug infusions such associations were far less significant. Infliximab treatment induced a significant reduction in the number of monocytes observed through the whole study (in all cases p < 0.05). CONCLUSION: Anti-TNF-alpha antibody therapy accompanied by MTX, beside a rapid clinical improvement, reduced serum chemokines concentrations in RA patients. Subsequent administrations of infliximab sustained chemokines decrease, although to a lesser extent than the first two dose of infliximab.