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

ID PMID Title PublicationDate abstract
20435928 Expanded CD23(+)/CD21(hi) B cells in inflamed lymph nodes are associated with the onset of 2010 Jun 1 Anti-CD20 B cell depletion therapy (BCDT) is very effective for some patients with rheumatoid arthritis (RA); however the pathogenic role of B lymphocytes in RA and the primary targets of BCDT are unknown. The human TNF transgenic (hTNF-Tg) mouse model of RA displays a chronic, progressive disease that spreads from distal to proximal joints and is generally considered to be adaptive immune system independent. We have previously reported that knee arthritis in hTNF-Tg mice is accompanied by structural and functional changes of the adjoining popliteal lymph node (PLN), detectable by contrast-enhanced magnetic resonance imaging. To better understand these changes, in this paper we show that onset of knee synovitis and focal erosions are paralleled by PLN contraction and accumulation of large numbers of B cells in the lymphatic sinus spaces within the node. Flow cytometry from TNF-Tg mice 2, 4-5, and 8-12 mo old demonstrated that B cell accumulation in the PLN follows ankle arthritis, but commences before knee disease, and involves early expansion of CD21(hi), CD23(+), IgM(hi), CD1d(+), activation marker-negative, polyclonal B cells that are found to be specifically restricted to lymph nodes draining inflamed, arthritic joints. The same B cell population also accumulates in PLNs of K/BxN mice with autoantigen-dependent arthritis. Strikingly, we show that BCDT ameliorates hTNF-Tg disease and clears follicular and CD21(hi), CD23(+) B cells from the PLNs. On the basis of these findings, we propose a model whereby B cells contribute to arthritis in mice, and possibly RA, by directly affecting the structure, composition, and function of joint-draining lymph nodes.
19700393 Dissection of the FCGR3A association with RA: increased association in men and with autoan 2010 Jun OBJECTIVES: Genome-wide association studies in rheumatoid arthritis (RA) have failed to examine the FCGR gene cluster because of the confounding effects of segmental duplication. This study aimed to replicate previous candidate gene studies that had identified a significant association between the FCGR3A-158V allele and RA and then sought to estimate specific subgroup effects. METHODS: FCGR3A-158F/V genotyping was undertaken in a UK Caucasian replication cohort comprising 2049 patients with RA and 1156 controls. Subgroup analyses assessing the magnitude of association according to gender and autoantibody (rheumatoid factor (RF) and cyclic citrullinated peptide (CCP)) status were undertaken in a pooled cohort of 2963 patients with RA and 1731 controls. Logistic regression was used to test for interaction between FCGR3A and HLA-DRB1 shared epitope (SE) alleles. RESULTS: In the combined RA cohort, borderline association with homozygosity was found for the FCGR3A-158V allele (OR 1.2, p=0.05), which was stronger in men (OR 1.7, p=0.01). Stratification by autoantibody status showed an increased risk in RF and CCP positive RA. Analysis of the FCGR3A-158V and HLA-DRB1 SE interaction revealed roles for both genes in susceptibility to autoantibody positive RA, with no evidence of interaction. CONCLUSIONS: FCGR3A is a risk factor for the development of autoantibody positive RA, particularly in men, with evidence of a multiplicative effect with HLA-DRB1 SE.
19954898 Validity and responsiveness of the Jebsen-Taylor Hand Function Test. 2010 Jan PURPOSE: The aim of this study was to demonstrate the validity and responsiveness of the Jebsen-Taylor Hand Function Test (JTT) in measuring hand function in patients undergoing hand surgery, compared with the Michigan Hand Outcomes Questionnaire (MHQ). METHODS: A prospective cohort of patients with rheumatoid arthritis (n = 37), osteoarthritis (n= 10), carpal tunnel syndrome (n = 18), and distal radius fracture (n = 46) were evaluated preoperatively and at 9 to 12 months of follow-up. We administered the JTT and MHQ. We performed correlation and receiver operating characteristic analyses to evaluate the validity of the JTT as a measure of disability. Effect size and standardized response means were calculated to determine responsiveness. RESULTS: Correlation studies revealed poor correlation of the JTT with MHQ total scores and subsets that relate to hand function. Patients with high MHQ scores generally perform well on the JTT; however, patients with good JTT scores do not necessarily have high MHQ scores. Receiver operating characteristic curves for each condition showed that the change in JTT total score had poor ability to discriminate between high and low MHQ score subjects, with an area under the curve result of 0.52 to 0.66 for each condition. Effect size and standardized response means for all states showed greater responsiveness with the MHQ for each condition compared with the JTT. CONCLUSIONS: We found poor correlation between the change in JTT and absolute JTT scores after surgery compared with change in MHQ and absolute MHQ scores. In addition, the JTT had poor discriminant validity based on the MHQ as a reference. This study showed that the time to complete activities does not correlate well with patient-reported outcomes. We conclude that the JTT should not be used as a measure of disability or clinical change after surgical intervention. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.
20805297 Effect of intra-articular corticosteroid injections and inflammation on periarticular and 2011 Jan OBJECTIVES: To explore the effect of intra-articular corticosteroid (IAST) injections on bone mineral density (BMD) in the hand and at the metacarpophalangeal (MCP) joints in early rheumatoid arthritis (RA). METHODS: In the first 3 months of the study, 19 patients with RA received methotrexate (MTX) alone and 21 received MTX and IAST injections into clinically inflamed joints. In the following 9 months, all patients received MTX+IAST. BMD was assessed at the hand and periarticular regions at MCP joints 2-5 at baseline, 3 and 12 months. RESULTS: In the first 3 months a numerically lower percentage rate of bone loss was seen in MTX+IAST-treated patients compared with MTX-treated patients. This observation was more pronounced at the MCP periarticular regions (eg, partial proximal phalanges: digit 2, -0.45% vs -2.69%, p=0.045; digit 3, -0.34% vs -3.32%, p=0.003; digit 4, -0.39% vs -2.57%, p=0.14; digit 5, -0.59% vs -2.70%, p=0.24) than for the whole hand (-1.53% vs -2.42%, p=0.32). In the 3-12-month period, only minor non-statistically significant differences were seen between the two groups. CONCLUSION: IAST given over 3 months protects against periarticular bone loss in inflamed finger joints in RA. These data emphasise the importance of suppressing inflammation in patients with active RA to maintain bone health.
19944558 Time-course of health status in patients with rheumatoid arthritis during the first year o 2010 Feb OBJECTIVES: A longitudinal study was performed to examine changes in health status in comparison with rheumatoid arthritis (RA) inflammation in patients with RA during the first 54 weeks of infliximab (IFX) treatment. METHODS: Health status in active RA patients (n=13) was assessed monthly using the Arthritis Impact Measurement Scale 2 (AIMS2) and the VAS-GH during the first year of IFX treatment. Simultaneously, RA activity was assessed using inflammation markers, MMP-3 and the Disease Activity Score in 28 joints (DAS-28) based on CRP [DAS-28(CRP)] and ESR[DAS-28(ESR)]. RESULTS: Serum CRP and ESR decreased significantly from 2.14+/-0.52mg/dL and 56.9+/-6.96mm/h, respectively, at baseline to 0.24+/-0.11mg/dL and 31.6+/-4.39mm/h, respectively, at 2 weeks after initiation of IFX. Other inflammatory markers and MMP-3 were also suppressed significantly after 2 weeks of IFX treatment. DAS-28(CRP) and DAS-28(ESR) were also significantly decreased after 2 weeks and suppression of both DAS values remained significant until 54 weeks of IFX treatment. After initiation of IFX, patient-reported general health also showed a significant improvement based on the changes in the six summary component scores on the AIMS2 (physical, affect, symptom, role, social interaction, and patient satisfaction). These scores all improved progressively until 14-18 weeks after initiation of IFX treatment, and then exhibited a temporary but insignificant exacerbation. The six components of the physical score also improved in a time-dependent manner until 14-18 weeks, but the scores for walking and bending, hand and finger function, arm function, self-care, and household tasks showed significant exacerbation at 22-30 weeks. The score for mobility level did not show this change. CONCLUSION: IFX treatment significantly improved both RA disease activity and health status in active RA patients. Time-dependent improvement of ADL until 14-18 weeks after initiation of IFX treatment, as reflected in the six components of the physical score, might have contributed to the temporary exacerbation of health status thereafter in these patients.
20506234 Generalized bone loss as a predictor of three-year radiographic damage in African American 2010 Aug OBJECTIVE: To examine the association between baseline bone mineral density (BMD) and radiographic damage at 3 years of disease duration in a longitudinal cohort of African Americans with recent-onset rheumatoid arthritis (RA). METHODS: African American RA patients with a disease duration of <2 years (n = 141) were included in the study. All patients underwent baseline BMD measurements (femoral neck and/or lumbar spine) using dual x-ray absorptiometry. T scores were calculated using normative data from the general population of African Americans. Patients were categorized as having osteopenia/osteoporosis (T score less than or equal to -1) or as being healthy. Hand and wrist radiographs, obtained at baseline and at 3 years of disease duration, were scored using the modified Sharp/van der Heijde method. The association between baseline BMD and total radiographic score at 3 years of disease was examined using multivariable negative binomial regression. RESULTS: At baseline, the mean age and the mean disease duration were 52.4 years and 14.8 months, respectively; 85.1% of the patients were women. The average total radiographic scores at baseline and at 3 years of disease were 2.4 and 5.7, respectively. In the final reduced multivariable model, adjusting for age, sex, anti-cyclic citrullinated peptide antibody positivity, and the presence of radiographic damage at baseline, the total radiographic score at 3 years disease in patients with osteopenia/osteoporosis of the femoral neck was twice that in patients with normal bone density, and the difference was statistically significant (P = 0.0084). No association between lumbar spine osteopenia/osteoporosis and radiographic score was found. CONCLUSION: Our findings suggest that reduced generalized BMD may be a predictor of future radiographic damage and support the hypothesis that radiographic damage and reduced generalized BMD in RA patients may share a common pathogenic mechanism.
21188454 Reduction in serum levels of substance P in patients with rheumatoid arthritis by etanerce 2011 Jun We determined the effects of etanercept on the serum concentrations of neuropeptides in RA patients. In a total of 11 patients who had been injected with etanercept, the serum levels of substance P, calcitonin gene-related peptide (CGRP), and gastrin-releasing peptide (GRP) were analyzed. Average levels of serum substance P were significantly reduced from 1.53 to 0.62 ng/ml after the injection of etanercept. In the CGRP and GRP analyses, these average levels dropped from 1.57 and 0.51 ng/ml to 0.44 and 0.04 ng/ml, respectively. Etanercept appears to decrease substance P levels with an improvement in disease activities.
18952480 Intra-articular botulinum toxin A as an adjunctive therapy for refractory joint pain in pa 2009 Mar We report the use of intra-articular Botulinum toxin A in two RA patients with persistently painful monoarthritis in ankle/feet joints. Both patients had monarticular pain despite a good response of all other joints to a combination therapy that included anti-tumor necrosis factor therapy. Both patients had failed intra-articular corticosteroid injections and declined surgical options. After a single, "off-label", intra-articular injection of Botulinum toxin A into the right ankle (100 unit) and left first metatarsophalangeal joint (25 unit), respectively, pain and function improved significantly (> or =40%) in both patients. Durable response with improvement of pain and function lasting 15-18 months was noted (follow-up continuing). Ankle joint swelling resolved by 15 months and MTP joint swelling by one month. Intra-articular BoNT/A may be an additional therapeutic option in RA patients with persistent monoarthritis. A randomized study is underway to confirm these findings.
21044440 Side effects and management of side effects of methotrexate in rheumatoid arthritis. 2010 Sep Low-dose methotrexate (MTX) remains the first-line treatment option among the disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. However, diverse side effects are the major reason for MTX withdrawal and change of treatment. The following article reviews the published data on general and organ-specific side effects and outlines the current recommendations addressing prevention and management of MTX-associated adverse effects.
20131234 Gene expression profiling in autoantibody-positive patients with arthralgia predicts devel 2010 Mar OBJECTIVE: To identify molecular features associated with the development of rheumatoid arthritis (RA), to understand the pathophysiology of preclinical development of RA, and to assign predictive biomarkers. METHODS: The study group comprised 109 anti-citrullinated protein antibody (ACPA)- and/or rheumatoid factor-positive patients with arthralgia who did not have arthritis but were at risk of RA, and 25 patients with RA. The gene expression profiles of blood samples obtained from these patients were determined by DNA microarray analysis and quantitative polymerase chain reaction. RESULTS: In 20 of the 109 patients with arthralgia who were at risk of RA, arthritis developed after a median of 7 months. Gene expression profiling of blood cells revealed heterogeneity among the at-risk patients, based on differential expression of immune-related genes. This report is the first to describe gene signatures relevant to the development of arthritis. Signatures significantly associated with arthritis development were involved in interferon (IFN)-mediated immunity, hematopoiesis, and chemokine/cytokine activity. Logistic regression analysis revealed that the odds ratio (OR) for developing arthritis within 12 months was 21.0 (95% confidence interval [95% CI] 2.8-156.1 [P = 0.003]) for the subgroup characterized by increased expression of genes involved in IFN-mediated immunity and/or cytokine/chemokine-activity. Genes involved in B cell immunology were associated with protection against progression to arthritis (OR 0.38, 95% CI 0.21-0.70 [P = 0.002]). These processes were reminiscent of those in patients with RA, implying that the preclinical phase of disease is associated with features of established disease. CONCLUSION: The results of this study indicate that IFN-mediated immunity, hematopoiesis, and cell trafficking specify processes relevant to the progression of arthritis independent of ACPA positivity. These findings strongly suggest that certain gene signatures have value for predicting the progression to arthritis, which will pave the way to preventive medicine.
19962615 Joint counts to assess rheumatoid arthritis for clinical research and usual clinical care: 2009 Nov A joint examination is prerequisite to a diagnosis of rheumatoid arthritis (RA), and quantitative counts of swollen and tender joints are the most specific of the 7 RA Core Data Set measures for patient assessment. Therefore, joint counts are weighted of greater importance than the other 5 Core Data Set measures in American College of Rheumatology response criteria and all RA indices in which it is included. Nonetheless, several limitations to the joint count have been recognized: (1) poor reproducibility with a requirement to be performed by the same observer at each visit; (2) likelihood to improve with placebo treatment as much or more than the other 5 RA Core Data Set measures; (3) similar or lower relative efficiencies than global and patient measures to document differences between active and control treatments in clinical trials; (4) improvement over 5 years while joint damage and functional disability may progress; (5) lower sensitivity in detecting inflammatory activity than ultrasound and magnetic resonance imaging. Most visits to a rheumatologist do not include a formal quantitative joint count. Quantitative patient self-report data are as sensitive to change and as informative about prognosis and outcomes as joint counts. It may be suggested that a careful qualitative (nonquantitative) joint examination, supplemented by quantitative self-report questionnaire scores to interpret physical examination findings, may be adequate to monitor patients and document changes in status in busy clinical settings.
20041492 Chondrogenic differentiation of human subchondral progenitor cells is impaired by rheumato 2010 Jun In microfracture, subchondral progenitors enter the cartilage defect and form cartilage repair tissue. We hypothesize that synovial fluid (SF) from rheumatoid arthritis (RA) donors affects chondrogenesis of human subchondral progenitors stimulated with transforming growth factor-beta3 (TGFB3), whereas SF from normal and osteoarthritis (OA) donors do not. Human progenitors from subchondral cortico-spongious bone (pool of n = 4) were cultured in micromasses under serum-free conditions and were stimulated with 10 ng/mL TGFB3 and with 5% SF from normal, OA, and RA donors (pool of n = 7, each). Histological staining of proteoglycan and immunostaining of type II collagen showed that progenitors stimulated with SF from RA donors show significantly reduced cartilage matrix formation compared to progenitors treated with TGFB3 or with SF from normal and OA donors (n = 3, each). Gene expression analysis of typical chondrocyte marker genes and genes encoding matrix modifying enzymes showed that SF from OA and RA donors influence the onset of TGFB3-mediated chondrogenesis (pool of 20 micromasses), but had no effect on the gene expression profile after prolonged culture in micromasses. These results suggest that SF from RA patients may impair the chondrogenic development of mesenchymal progenitors in microfracture, whereas osteoarthritic SF may has no negative effect on the cartilage matrix formation.
20858791 Contrast-enhanced whole-body joint MRI in patients with unclassified arthritis who develop 2010 Oct OBJECTIVE: The purpose of this article is to examine the feasibility of whole-body joint MRI for detecting systemic joint synovitis and for analyzing the relationship between the hands and systemic joint involvement in patients with unclassified arthritis who later develop early rheumatoid arthritis (RA). MATERIALS AND METHODS: The study included 17 patients (five men and 12 women; median age, 65 years [range, 38-77 years]; median symptom duration, 3 months [range, 1-6 months]). MRI of the systemic joints was performed for patients with unclassified arthritis without radiographic evidence of RA and who were diagnosed as having RA according to 1987 revised classification criteria within 2 years. RESULTS: The chosen 4-point scale for image quality was moderate to excellent. MRI findings of systemic joints were in accordance with joint swelling and tenderness (chi-square test, p < 0.0001). Sixty percent (45/75) of hand joints and 67% (12/18) of systemic joints other than hands showed MR synovitis without swelling. With regard to the correlation of MRI findings between hands and joints other than hands, there was a statistically significant positive correlation in the joint count (r = 0.5514 and p = 0.0218) and semiquantitative value of hand synovitis (r = 0.5382 and p = 0.0258). CONCLUSION: Whole-body joint MRI in early RA is feasible in terms of image quality and agreement with the results of clinical examination. MRI may be more sensitive for depicting synovitis-positive joints than clinical examination. Estimation of the systemic burden of synovitis detected by MRI may be possible via MRI of the hands.
19040300 Telomerase transduced osteoarthritis fibroblast-like synoviocytes display a distinct gene 2009 Jan OBJECTIVE: To examine the differential gene expression in telomerase transduced osteoarthritis fibroblast-like synoviocytes (hTERT-OA 13A FLS) and telomerase transduced rheumatoid arthritis FLS (hTERT-RA 516 FLS) and test the hypothesis that longterm culture of hTERT-OA 13A FLS display a disease-specific gene expression profile. METHODS: Gene expression in passage 8 hTERT-OA 13A FLS and passage 8 hTERT-RA 516 FLS were compared using microarray assays. Differential expression of selected genes was further examined by reverse transcription-polymerase chain reaction (RT-PCR). After continuous expansion in culture for an additional 4 months, gene expression in the longterm cultures of hTERT-OA 13A FLS and hTERT-RA 516 FLS was again examined with microarray and real-time RT-PCR. RESULTS: hTERT-OA 13A FLS displayed a distinct gene expression profile. While hTERT-RA 516 FLS expressedADAMTS1, ADAMTS3, ADAMTS5, and several carboxypeptidases, hTERT-OA 13A FLS expressed matrix metalloproteinase (MMP)1, MMP3, and several cathepsins at higher levels. Numerous genes classified in the immune response, lipid transport/catabolism, and phosphate transport biological processes were also expressed at higher levels in hTERT-OA 13A FLS. In contrast, numerous genes classified in the positive regulation of cell proliferation, anti-apoptosis, and angiogenesis biological processes were expressed at higher levels in hTERT-RA 516 FLS. Further, of the recently proposed 21 candidate synovial biomarkers of OA, 12 (57%) were detected in our study. CONCLUSION: The findings indicate that OA FLS may not be a passive bystander in OA and that telomerase transduced OA FLS offer an alternative tool for the study of synovial disease markers and for the identification of new therapeutic targets for OA therapy.
20155834 Antiinflammatory effects of tumor necrosis factor on hematopoietic cells in a murine model 2010 Jun OBJECTIVE: To investigate the mechanisms leading to the influx of inflammatory hematopoietic cells into the synovial membrane and the role of tumor necrosis factor receptor I (TNFRI) and TNFRII in this process in an animal model of rheumatoid arthritis (RA). METHODS: We performed bone marrow transplantations in human TNF-transgenic mice using hematopoietic cells from wild-type, TNFRI(-/-), TNFRII(-/-), and TNFRI/II(-/-) mice as donors and assessed the severity of arthritis histologically. Generation of osteoclasts from the different genotypes was analyzed in vitro and in vivo. Apoptosis was analyzed using annexin V staining as well as TUNEL assays. RESULTS: Despite lacking responsiveness to TNF in their hematopoietic compartment, mice not only developed full-blown erosive arthritis but even showed increased joint destruction when compared with mice with a TNF-responsive hematopoietic compartment. We demonstrated different roles of the 2 different TNFRs in the regulation of these processes. The absence of TNFRI on hematopoietic cells did not affect joint inflammation but markedly attenuated erosive bone destruction via reduced synovial accumulation of osteoclast precursors. In contrast, the absence of TNFRII on hematopoietic cells increased joint inflammation as well as erosive bone destruction via the regulation of osteoclast precursor apoptosis. CONCLUSION: Our findings indicate that selective blockade of TNFRI, leaving the antiinflammatory effects of TNFRII unaltered instead of unselectively blocking TNF, might be advantageous in patients with RA.
19877045 Association of higher rheumatoid arthritis disease activity during pregnancy with lower bi 2009 Nov OBJECTIVE: To determine the outcome of pregnancy in women with rheumatoid arthritis (RA) in relation to disease activity and medication use during the pregnancy. METHODS: In a prospective study, pregnant women with RA were evaluated before conception (when possible), during each trimester of the pregnancy, and postpartum. Clinical characteristics, disease activity, medication use, and pregnancy outcome were analyzed. To examine the independent influence of prednisone use and disease activity on birth weight, regression analyses were performed, with adjustments for gestational age of the child at delivery, the sex of the newborn, and the mother's smoking status, education level, parity, and use of an assisted reproduction technique. Kaplan-Meier curve analyses were performed to examine the association between medication use and gestational age at delivery. RESULTS: Data from 152 Caucasian RA patients with singleton pregnancies were available. Both the mean +/- SD birth weight (3,379 +/- 564 gm) and the mean +/- SD birth weight standard deviation score (SDS; +0.1 +/- 1.1), which is the birth weight adjusted for the gestational age and sex of the newborn, were comparable with those in the general population. On multiple linear regression analyses of birth weight and birth weight SDS, both of which were adjusted for covariates, only disease activity was associated with lower birth weight (P = 0.025). The gestational age at delivery was significantly lower in women who were taking prednisone (38.8 versus 39.9 weeks; P = 0.001), and their delivery was more often premature (<37 weeks; P = 0.004). CONCLUSION: Pregnancy outcome in women with well-controlled RA is comparable with that in the general population. The effect of prednisone on birth weight is mediated by a lower gestational age at delivery, whereas a higher level of disease activity independently influences birth weight negatively, suggesting an immune-mediated mechanism.
20369613 [Peculiarities of therapy of neurotic disorders in patients with rheumatoid arthritis]. 2010 Evaluation of neurotic disorders (ND) in 168 patients with rheumatoid arthritis revealed them in 65.6% of the cases including 22.6% weak, 31.7% moderate and 14.9% severe ones. Asthenovegetative disorders were most frequently detected (61.3%). They associated with emotional, hypochondriac, hysterical, and obsessional disorders in 24.4, 14.3, 9.5, and 4.8% of the patients respectively. ND were treated depending on their type and severity. Mild ND were managed by combined therapy including general tonics, physiotherapeutic procedures, and remedial gymnastics. Patients with moderate ND were given sedative medicines (novopassit, sedavit, glycine, peony tincture). Severe ND were managed using antidepressants and tranquilizers. Duration of therapy was 10-21 days depending on its form. The treatment eliminated all symptoms of ND in 66 (54.1%) and reduced them in 44 (36.1%) of the patients. The outcome of psychotherapy was regarded as unsatisfactory in 11.5%, satisfactory in 26.2%, and positive in 62.3% of the patients. These values in a control group of 46 patients without HD were 10.8, 37.0, and 52.2% respectively.
19714713 The use of post-translationally modified peptides for detection of biomarkers of immune-me 2009 Oct Biomarkers are decision-making tools at the basis of clinical diagnostics and essential for guiding therapeutic treatments. In this context, autoimmune diseases represent a class of disorders that need early diagnosis and steady monitoring. These diseases are usually associated with humoral or cell-mediated immune reactions against one or more of the body's own constituents. Autoantibodies fluctuating in biological fluids can be used as disease biomarkers and they can be, thus, detected by diagnostic immunoassays using native autoantigens. However, it is now accepted that post-translational modifications may affect the immunogenicity of self-protein antigens, triggering an autoimmune response and creating neo-antigens. In this case, post-translationally modified peptides represent a more valuable tool with respect to isolated or recombinant proteins. In fact, synthetic peptides can be specifically modified to mimic neo-antigens and to selectively detect autoantibodies as disease biomarkers. A 'chemical reverse approach' to select synthetic peptides, bearing specific post-translational modifications, able to fishing out autoantibodies from patients' biological fluids, can be successfully applied for the development of specific in vitro diagnostic/prognostic assays of autoimmune diseases. Herein, we report the successful application of this approach to the identification of biomarkers in different autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.
19275023 Management of foot ulceration in patients with rheumatoid arthritis. 2009 Feb 18 Patients with rheumatoid arthritis (RA) are at increased risk of developing foot ulceration. A multidisciplinary approach to the assessment, management and treatment of foot ulceration is essential to improve patient outcomes and reduce recurrence rates of ulceration. This article outlines the management and prevention of foot ulceration in patients with RA and promotes best practice.
19790118 Skeletal health among African Americans with recent-onset rheumatoid arthritis. 2009 Oct 15 OBJECTIVE: African Americans with rheumatoid arthritis (RA) may be at increased fracture risk. We applied the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Foundation (NOF) guidelines to a cohort of African Americans with early RA to identify which patients were recommended for osteoporosis treatment. METHODS: Risk factors and bone mineral density (BMD) were assessed in a cohort of African Americans with RA. The WHO FRAX tool estimated 10-year fracture risk. Patients were risk stratified using FRAX without BMD to identify which individuals might be most efficiently targeted for BMD testing. RESULTS: Participants (n = 324) had a mean age of 51 years and included 81% women. There were no associations of RA disease characteristics with BMD. The proportion of patients recommended for osteoporosis treatment varied from 3-86%, depending on age and body mass index (BMI). Ten-year fracture risk calculated with BMI only was generally the same or higher than fracture risk calculated with BMD; adding BMD data provided the most incremental value to risk assessment in patients 55-69 years of age with low/normal BMI, and in those > or =70 years of age with BMI > or =30 kg/m2. CONCLUSION: A high proportion of African Americans with RA were recommended for treatment under the 2008 NOF guidelines. FRAX without BMD identified low-risk patients accurately. Systematic application of FRAX to screen high-risk groups such as patients with RA may be used to target individuals for BMD testing and reduce the use of unnecessary tests and treatments.