Browse

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

ID PMID Title PublicationDate abstract
22512551 Cyclin-dependent kinase inhibition by flavoalkaloids. 2012 Jun Chromone alkaloids and flavoalkaloids are an important group of natural products possessing promising medicinal properties. A chromone alkaloid rohitukine is a major bioactive chemical constituent of plant Dysoxylum binectariferum (Meliaceae) Hook. which is phylogenetically related to the Ayurvedic plant, D. malabaricum Bedd. used for treatment of rheumatoid arthritis. This chromone alkaloid led to discovery of two synthetic flavoalkaloids: flavopiridol (Sanofi) and P-276-00 (Piramal) which have reached to advanced stages of clinical development for cancer treatment. Flavopiridol (Alvocidib; L868275; HMR-1275; NSC 649890 of Sanofi-Aventis + NCI) is approved as an orphan drug for treatment of chronic lymphocytic leukemia and is currently undergoing phase II studies as monotherapy and also as in combination regimes with traditional chemotherapy agents. P-276-00 (12) is currently in phase II clinical studies for advanced refractory neoplasms and multiple myeloma. Extensive amount of medicinal chemistry efforts have been reported on these flavoalkaloids. Flavopiridol demonstrated potent and specific in vitro inhibition of variety of cyclindependent kinases with clear block in cell cycle progression at the G1/S and G2/M phases. Preclinical studies demonstrated the capacity of flavopiridol to induce programmed cell death, promote differentiation, inhibit angiogenic processes and modulate transcriptional events. The co-crystallised structure of deschloro-flavopiridol with CDK-2 is available and key interactions in the ATP binding site have been reported. Flavopiridol has also been studied for the treatment of arthritis and atherosclerotic plaque formation. The present review comprises discovery, medicinal chemistry, pharmacology and preclinical/clinical development of flavoalkaloids as CDK inhibitors.
22080861 Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase dr 2011 Dec Genome-wide association studies (GWAS) have identified a large number of SNPs that are linked to human autoimmune diseases. However, the functional consequences of most of these genetic variations remain undefined. T cell protein tyrosine phosphatase (TCPTP, which is encoded by PTPN2) is a JAK/STAT and growth factor receptor phosphatase that has been linked to the pathogenesis of type 1 diabetes, rheumatoid arthritis, and Crohn's disease by GWAS. In this issue of the JCI, Wiede and colleagues have generated a T cell-specific deletion of TCPTP and identified a novel role for this phosphatase as a negative regulator of TCR signaling. These data provide new insight as to how noncoding PTPN2 SNPs identified in GWAS could drive human autoimmune diseases.
22124592 Anti-citrullinated peptide antibodies and rheumatoid factor in Sudanese patients with Leis 2011 Dec OBJECTIVE: The present study evaluated the presence of anti-cyclic citrullinated peptides antibodies (anti-CCP), rheumatoid factor (RF), and circulating immune complexes (CIC) in Sudanese patients infected with the Leishmania donovani parasite. PATIENTS AND METHODS: Sera were collected from Leishmania infected patients (n = 116) and healthy Sudanese (n = 93). Nineteen Sudanese anti-CCP+ RA patients were included as positive controls. Levels of CIC and anti-CCP were measured by ELISA. Control plate with cyclic control peptides containing arginine instead of citrulline was used to evaluate citrulline specifi c reactivity. RESULTS: Among Leishmania-infected patients and anti-CCP+ RA patients, most were RF positive (86%), while the frequency of CIC positivity was higher among visceral leishmaniasis (VL) patients (VL 38%; anti-CCP+ RA 24%). When anti-CCP reactivity was analysed, 12% of VL patients were found to be positive. The levels of anti-CCP among VL patients correlated well with the CIC levels found (r = 0.65, P < 0.0001). In RA group, no association was found between CIC and anti-CCP. The possibility that anti-CCP positivity was due to cross reactions with CIC was experimentally ruled out. Contrary to what was seen in Sudanese RA sera, the CCP reactivity was not restricted to citrulline but reacted equally well with the arginine control peptide. CONCLUSION: The finding that CCP reactivity was not restricted to citrulline argues that this is more an effect of extensive inflammation and immune activation than a sign of shared pathogenic characteristics with anti-CCP arthritis. Our fi ndings stress the importance to interpret a positive CCP test carefully when evaluated in non-rheumatic conditions or in areas where such infections predominate.
20680378 Clinical findings in parvovirus B19 infection in 30 adult patients in Kyoto. 2011 Feb To relate the clinical findings of parvovirus B19 infection to the phase of the disease, we performed a retrospective chart review of 30 adult patients who tested positive for IgM antibody against parvovirus B19 at our hospital from March 2003 to November 2008. Median patient age was 38 years, with 86.7% aged between 26 and 45 years. The male-to-female ratio was 4:26 (86.7% female). Symptoms in the first phase were mainly flu-like, including fever, headache, or myalgia. Symptoms in the second phase were arthralgia in 24 (85.7%) and rash in 23 (82.1%). Fever was observed in 21 (70.0%), and 22 (75.9%) were found to be lymphopenic. The onsets in 73.3% of cases were concentrated within 10.1% of the study period, an observation nearly consistent with an outbreak of erythema infectiosum. Three patients had symmetrical swelling of joints, all of whom also had rash. Most patients visited the hospital within a week of onset and prognosis was favorable. In the parvovirus B19 infection, flu-like symptoms were frequent in the first phase, while rash and arthralgia were common in the second. Female sex, age between 26 and 45, and presence of rash, arthralgia, fever, and lymphopenia were clinical findings with a high frequency (≥70%), and these factors may contribute to diagnosis. In an era when early diagnosis and therapy is required in rheumatoid arthritis, it is important to recognize the parvovirus B19 infection with a presentation of acute arthritis and a favorable prognosis.
23253932 Effect of IL-17A blockade with secukinumab in autoimmune diseases. 2013 Apr Genetic studies and correlative expression data in diseased tissues have pointed to the role of interleukin (IL)-17 and Th17 cells in the pathogenesis of autoimmune disorders such as psoriasis, inflammatory bowel disease and seronegative spondyloarthropathies. Th17 cells are known to produce the proinflammatory cytokine IL-17A as well as other effector cytokines, including IL-17F and IL-22. Recent research has demonstrated that IL-17A is also expressed by multiple lineages of the innate immune system, including mast cells, neutrophils, dendritic cells, γδ-T cells, macrophages and natural killer cells. It can thus be expected that the inhibition of IL-17A as a therapeutic target in autoimmune disease would exert different physiological effects than the suppression of Th17 cell activity. Early clinical data are now available on secukinumab (AIN457), a recombinant, highly selective, fully human monoclonal anti-IL-17A antibody of the IgG1/κ isotype, enabling a preliminary assessment of the effects of IL-17A inhibition in multiple autoimmune diseases. Rapid and sustained symptom reductions in psoriasis, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have been observed in secukinumab-treated patients, with no overt safety signals. In conjunction with studies using the humanised anti-IL-17A monoclonal antibody (mAb) ixekizumab (LY2439821) and the fully human anti-IL-17RA mAb brodalumab (AMG 827), the findings on secukinumab provide evidence for the role of IL-17A in the pathophysiology of autoimmune disease and suggest the potential value of targeting this cytokine.
23197053 Corticoid-associated complications in elderly. 2012 Nov BACKGROUND: Corticosteroids are widely prescribed products in the elderly particularly in systemic diseases. Corticosteroids were indispensable in controlling a variety of disease states. Various complications associated with this drug class warrant caution and monitoring with each formulation especially with old population. AIM: To evaluate the frequency and type of side effects and complications of long-term corticosteroid therapy in the elderly. METHODS: We conducted a retrospective study of 23 patients aged 65 and older hospitalized in the internal medicine department of the Habib Thameur hospital during January 2000 to December 2004. Corticoid adverse effects were recorded throughout the follow up period. RESULTS: There are 20 women and 3 men aged 66 to 87 years with a mean age of 75.7 years. The diagnoses were 8 cases of temporal arteritis, 7 cases of rheumatoid arthritis, 3 cases of multiple myeloma, 2 scleroderma, 1 case of systemic lupus erythematosus, 1 case of retroperitoneal fibrosis and 1 case of psoriatic arthritis. We selected 66 complications. Infectious complications were found in 26 cases (39.3%), 11 cases (16.7%) of iatrogenic diabetes, arterial hypertension in 9 cases (13%), skeletal complications in both cases,psychiatric complications in two cases, ophthalmologic complications in one case. CONCLUSION: Despite lifestyle rules and adjunctive therapy, complications seem to be frequent. To minimize the disadvantages of prolonged corticosteroid treatment, regular monitoring and careful screening is imperative for the support and time.
23021982 Eph/Ephrin signaling in injury and inflammation. 2012 Nov The Eph/ephrin receptor-ligand system plays an important role in embryogenesis and adult life, principally by influencing cell behavior through signaling pathways, resulting in modification of the cell cytoskeleton and cell adhesion. There are 10 EphA receptors, and six EphB receptors, distinguished on sequence difference and binding preferences, that interact with the six glycosylphosphatidylinositol-linked ephrin-A ligands and the three transmembrane ephrin-B ligands, respectively. The Eph/ephrin proteins, originally described as developmental regulators that are expressed at low levels postembryonically, are re-expressed after injury to the optic nerve, spinal cord, and brain in fish, amphibians, rodents, and humans. In rodent spinal cord injury, the up-regulation of EphA4 prevents recovery by inhibiting axons from crossing the injury site. Eph/ephrin proteins may be partly responsible for the phenotypic changes to the vascular endothelium in inflammation, which allows fluid and inflammatory cells to pass from the vascular space into the interstitial tissues. Specifically, EphA2/ephrin-A1 signaling in the lung may be responsible for pulmonary inflammation in acute lung injury. A role in T-cell maturation and chronic inflammation (heart failure, inflammatory bowel disease, and rheumatoid arthritis) is also reported. Although there remains much to learn about Eph/ephrin signaling in human disease, and specifically in injury and inflammation, this area of research raises the exciting prospect that novel therapies will be developed that precisely target these pathways.
22789463 A meta-analysis of mortality in rheumatic diseases. 2012 Nov INTRODUCTION: Data reporting mortality in rheumatic diseases vary widely. The objective of this systematic review and meta-analysis of published data is to provide an accurate overview of the current risk of mortality in rheumatic diseases. METHODS: Systematic review and meta-analysis of published studies identified by a sensitive search using free text and MeSH synonyms of "mortality" and of "rheumatic diseases", in general and by specific diagnoses. Eligibility criteria were (1) study population with rheumatoid arthritis, systemic lupus erythemathosus, systemic sclerosis, vasculitis, osteoarthritis, osteoporosis, dermatomyositis, or spondyloarthritis; (2) outcome of interest mortality, reported as an standardized mortality ratio (SMR), or easily calculated from data reported; and (3) cohorts or longitudinal observational studies. Assessment of risk of bias relied on the New Castle-Ottawa scale for cohorts; only moderate to high quality studies were included. Separate meta-SMRs were calculated for specific diagnoses. Heterogeneity was studied with meta-regression. RESULTS: A total of 32 studies were included, none in spondyloarthritis or osteoarthritis. The overall pooled SMR was 2.03 (95% confidence interval (CI) 1.79-2.29), ranging from 1.36 in psoriatic arthritis to 4.80 in vasculitis. The largest individual overall SMR came from studies on inflammatory diseases, and the specific SMR were very high for infections and pulmonary events. Heterogeneity between studies was large; however, the analysis of such heterogeneity within diseases did not provide any association with the collected variables. CONCLUSIONS: Based on our results and on the good quality of the included studies, we can conclude that rheumatic diseases increase in general the risk of death, and especially inflammatory diseases.
22160046 Successes and failures of stem cell transplantation in autoimmune diseases. 2011 Over the past 15 years, more than 1500 patients have received HSCT, mostly autologous, as treatment for a severe autoimmune disease (AD). More than 1000 of these have been registered in the European Group for Bone Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR) combined database. A recent retrospective analysis of 900 patients showed that the majority had multiple sclerosis (MS; n = 345) followed by systemic sclerosis (SSc; n = 175), systemic lupus erythematosus (SLE; n = 85), rheumatoid arthritis (RA; n = 89), juvenile idiopathic arthritis (JIA; n = 65), and idiopathic cytopenic purpura (ITP; n = 37). An overall 85% 5-year survival and 43% progression-free survival was seen, with 100-day transplantation-related mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Approximately 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many patients, such as in those with SSc, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented beyond any predicted known effects of intense immunosuppression alone. The high TRM was in part related to conditioning intensity, comorbidity, and age, but until the results of the 3 prospective randomized trials are known, an evidence-based modification of the conditioning regimen will not be possible.(1) In recent years, multipotent mesenchymal stromal cells (MSCs) have been tested in various AD, exploiting their immune-modulating properties and apparent low acute toxicity. Despite encouraging small phase 1/2 studies, no positive data from randomized, prospective studies are as yet available in the peer-reviewed literature.
21910626 Therapeutic targeting of the interleukin-6 receptor. 2012 Interleukin (IL)-6 is a typical cytokine featuring redundancy and pleiotropic activity. It contributes to host defense against pathogens, but dysregulation of IL-6 production plays a significant pathological role in various autoimmune and inflammatory diseases. Because IL-6 blockade was expected to constitute a novel strategy for the treatment of such diseases, tocilizumab, a humanized anti-IL-6 receptor antibody (anti-IL-6RAb), was developed. Clinical trials have demonstrated the efficacy of anti-IL-6RAb for patients with rheumatoid arthritis, Castleman's disease, and juvenile idiopathic arthritis, resulting in approval of this innovative biologic for the treatment of these diseases, and it can be expected to become a novel drug for various other autoimmune and inflammatory diseases. In murine models of autoimmune diseases, anti-IL-6RAb induces Treg and inhibits Th17 and/or Th1 differentiation, indicating that anti-IL-6RAb may be able to repair Th17/Treg imbalance in human diseases as well.
21904462 Update on the management of inflammatory bowel disease: specific role of adalimumab. 2011 Anti-tumor necrosis factor alpha (TNF-α) medications are a class of biologics employed in the treatment of patients with inflammatory bowel disease (IBD). Adalimumab is the first fully human monoclonal immunoglobulin directed against TNF-α, which binds with high affinity and specificity to membrane and soluble TNF. Adalimumab administered subcutaneously has demonstrated efficacy in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and severe chronic psoriasis. Studies have shown that adalimumab is effective for inducing and maintaining remission of moderate-to-severe active Crohn's disease (CD) patients at an induction dose of 160/80 mg (week 0 and 2) and at a maintenance dose of 40 mg every other week. The efficacy of adalimumab as a second-line therapy has also been documented for patients with loss of response or intolerance to infliximab. Adalimumab is also superior to placebo for inducing and maintaining complete perianal fistula closure. It also seems effective for reducing extraintestinal manifestations. The safety profile is similar to that of other anti-TNF therapy in CD patients, with lower immunogenicity and rate of adverse injection reactions than infliximab. Adalimumab is not approved for the treatment of ulcerative colitis (UC). Recently, however, the results of the first randomized, controlled trial on adalimumab for UC showed that adalimumab at 160/80 mg induction dose was safe and effective for inducing remission and clinical response after 8 weeks in patients with moderately-to-severely active UC failing treatment with corticosteroids and/or immunosuppressants. More data are necessary to clarify the therapeutic role of adalimumab in UC. This review of the literature summarizes available data on the efficacy and safety profile adalimumab in patients with IBD.
22021512 Arthroplasty of the hand: radiographic outcomes of pyrolytic carbon proximal interphalange 2011 Nov OBJECTIVE: The purpose of this study was to describe the radiographic outcomes of pyrolytic carbon implants in the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints, determine the most common complications, and assess risk factors associated with complications. MATERIALS AND METHODS: Retrospective review over a 10-year period was performed to identify patients with pyrolytic carbon implants of the PIP or MCP joint. All available radiographs were reviewed and correlated with clinical information. Statistical analysis included calculation of the complication rate, Phi coefficient for variable association with a complication, and Kaplan-Meier survival. RESULTS: Forty-seven implants in 43 patients were reviewed. There were 30 PIP and 17 MCP implants. The mean age of the patients was 56 years. The mean radiographic follow-up was 17.2 months (range, 1-82 months). The indication for arthroplasty included osteoarthritis (55.3%), trauma (27.7%), rheumatoid arthritis (12.8%), and benign neoplasm (4.26%). Fourteen second surgeries were performed: four for retrieval and 10 for revision. Radiographic abnormalities included subsidence (31.9%); loosening with dorsal or volar tilt of the stem (34.1%); loosening without tilt (6.38%); periprosthetic fracture (8.51%); and ulnar subluxation of joint (4.26%). There was no statistical association (r < 0.001) between 1 mm or less of symmetric lucency around the distal implant with future complications. The sensitivity of radiography for the clinical failure of the implant was 28.6% and specificity, 30.3%. CONCLUSION: Of the 47 pyrolytic carbon PIP and MCP implants, 14 (29.8%) required surgical revision or retrieval, mostly for extensor tendon contractures. Compared with the clinical survival of the implant, radiographic survival was poorer and did not correlate with clinical survival. Tilt of the proximal stem and subsidence were the more common radiographic complications.
21826801 A systems biology approach to synovial joint lubrication in health, injury, and disease. 2012 Jan The synovial joint contains synovial fluid (SF) within a cavity bounded by articular cartilage and synovium. SF is a viscous fluid that has lubrication, metabolic, and regulatory functions within synovial joints. SF contains lubricant molecules, including proteoglycan-4 and hyaluronan. SF is an ultrafiltrate of plasma with secreted contributions from cell populations lining and within the synovial joint space, including chondrocytes and synoviocytes. Maintenance of normal SF lubricant composition and function are important for joint homeostasis. In osteoarthritis, rheumatoid arthritis, and joint injury, changes in lubricant composition and function accompany alterations in the cytokine and growth factor environment and increased fluid and molecular transport through joint tissues. Thus, understanding the synovial joint lubrication system requires a multifaceted study of the various parts of the synovial joint and their interactions. Systems biology approaches at multiple scales are being used to describe the molecular, cellular, and tissue components and their interactions that comprise the functioning synovial joint. Analyses of the transcriptome and proteome of SF, cartilage, and synovium suggest that particular molecules and pathways play important roles in joint homeostasis and disease. Such information may be integrated with physicochemical tissue descriptions to construct integrative models of the synovial joint that ultimately may explain maintenance of health, recovery from injury, or development and progression of arthritis.
22697500 Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic 2012 Jun 14 INTRODUCTION: Semaphorin 3A (sema3A) and neuropilin-1 (NP-1) play a regulatory role in immune responses and have a demonstrated effect on the course of collagen induced arthritis. This study was undertaken to evaluate the role of sema3A and NP-1 in the pathogenesis of systemic lupus erythematosus (SLE) and the specific effect of sema3A on the auto-reactive properties of B cells in SLE patients. METHODS: Thirty two SLE and 24 rheumatoid arthritis (RA) patients were assessed and compared with 40 normal individuals. Sema3A serum levels were measured and correlated with SLE disease activity. The in vitro effect of sema3A in reducing Toll-like receptor 9 (TLR-9) expression in B cells of SLE patients was evaluated. RESULTS: Sema3A serum levels in SLE patients were found to be significantly lower than in RA patients (55.04 ± 16.30 ng/ml versus 65.54 ± 14.82 ng/ml, P = 0.018) and lower yet than in normal individuals (55.04 ± 16.30 ng/ml versus 74.41 ± 17.60 ng/ml, P < 0.0001). Altered serum sema3A levels were found to be in inverse correlation with SLE disease activity, mainly with renal damage. The expression of both sema3A and NP-1 on B cells from SLE patients was significantly different in comparison with normal healthy individuals. Finally, when sema3A was co-cultured with cytosine-phosphodiester-guanine oligodeoxynucleotides (CpG-ODN)-stimulated B cells of SLE patients, their TLR-9 expression was significantly reduced, by almost 50% (P = 0.001). CONCLUSIONS: This is the first study in which a reduced serum level of sema3A was found in association with SLE disease activity. It also raises the possibility that sema3A may have a regulatory function in SLE.
22422491 Clinical features of late-onset ankylosing spondylitis: comparison with early-onset diseas 2012 May OBJECTIVE: Ankylosing spondylitis (AS) is generally observed in young patients but can occur later in life or in persons ≥ 50 years of age. Our objective was to characterize the clinical features of late-onset AS in a large multicenter national cohort. METHODS: We studied late-onset AS in the National Registry of Spondyloarthritis of the Spanish Society of Rheumatology (REGISPONSER database) cohort (n = 1257), of whom 3.5% had onset at age ≥ 50 years versus a control group with onset at < 50 years. RESULTS: There were no differences between late-onset and early-onset AS according to sex and family history of spondyloarthropathies. Patients in the late-onset group more often showed involvement of the cervical spine (22.7% vs 9.7%; p = 0.03) and arthritis of the upper (13.6% vs 3.0%; p = 0.002) and lower limbs (27.3% vs 15.2%; p = 0.03) as first manifestations than did patients in the early-onset group. A higher percentage of mixed forms (axial and peripheral joint disease) during the course of the disease was also recorded in the late-onset group (50% vs 24%; p = 0.0001). CONCLUSION: Our study suggests that age at onset of AS affects the patients' presenting clinical form. Arthritis of the upper limbs requires a differential diagnosis with other conditions frequent in patients over 50 years of age, such as rheumatoid arthritis or crystal-induced arthropathy.
21321996 Adiponectin increases MMP-3 expression in human chondrocytes through AdipoR1 signaling pat 2011 May Articular adipose tissue is a ubiquitous component of human joints, and adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and involved in energy homeostasis. The adiponectin is significantly higher in synovial fluid of patients with osteoarthritis and rheumatoid arthritis. Matrix metalloproteinases (MMP)-3 may contribute to the breakdown of articular cartilage during arthritis. We investigated the signaling pathway involved in MMP-3 caused by adiponectin in human chondrocytes. Adiponectin increased the secretion of MMP-3 in cultured human chondrocytes, as shown by qPCR, Western blot, and ELISA analysis. Adiponectin-mediated MMP-3 expression was attenuated by AdipoR1 but not AdipoR2 siRNA. Pretreatment with 5'-AMP-activated protein kinase (AMPK) inhibitor (araA and compound C), p38 inhibitor (SB203580), and NF-κB inhibitor (PDTC and TPCK) also inhibited the potentiating action of adiponectin. Activations of p38, AMPK, and NF-κB pathways after adiponectin treatment were demonstrated. Taken together, our results provide evidence that adiponectin acts through AdipoR1 to activate p38 and AMPK, resulting in the activations of NF-κB on the MMP-3 promoter and contribute cartilage destruction during arthritis.
20706991 Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 a 2011 Feb We investigated the effects of hyaluronan (HA) on interleukin-1β (IL-1β)-stimulated matrix metalloproteinase (MMP)-13 production in human chondrocytes from patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Secreted levels of MMP-13 in conditioned media were detected by immunoblotting, while intracellular MMP-13 synthesis in articular cartilage was evaluated by immunofluorescence microscopic analysis. Mitogen-activated protein kinases (MAPKs), p38, extracellular signal-regulated kinases (ERK), and c-jun NH2-terminal kinase (JNK) were assessed by Western blotting. IL-1β (2 ng/ml) stimulates the secretion of MMP-13 in both OA and RA chondrocytes. Inhibition studies using specific MAPK inhibitors revealed that IL-1β induced MMP-13 via p38 in both OA and RA chondrocytes. HA down-regulates IL-1β-stimulated MMP-13 and phosphorylated p38 (p-p38) in a dose-dependent manner (0.1, 1, 2, and 4 mg/ml). When used at 4 mg/ml, HA inhibits p-p38 phosphorylation by more than 60%. In response to IL-1β, RA chondrocytes express a higher level of p-p38 than that of OA chondrocytes. Inhibition of CD44, using a blocking antibody, significantly reversed the inhibitory effect of HA on both MMP-13 and p-p38. Our study clearly shows that HA inhibits IL-1β-induced MMP-13 via its principal receptor, CD44, and subsequent intracellular p38 MAPK signaling in OA and RA chondrocytes.
21739620 Rheumatologists on the road: a subspecialist's role in caring for the homebound. 2011 Oct OBJECTIVE: By 2030, the number of permanently homebound individuals in the US will increase by 50% to reach 2 million. However, no medicine subspecialty consult services exist for this rising subset of the population. This pilot program establishes a rheumatology consult service for the Mount Sinai Visiting Doctors, the largest primary care academic home visit program in the nation serving more than 1,000 patients in New York City. Our service addresses the unmet need for homebound patients with rheumatic diseases, and secondarily provides an educational opportunity for trainees in community-based rheumatology. METHODS: Using an electronic medical record, home-based primary care physicians sent consult requests to the Rheumatology Division. Initial assessments were made using the Routine Assessment of Patient Index Data 3 (RAPID3) questionnaire. RESULTS: Over 12 months, 57 home visits were made: 31 new consults and 26 followup visits. Reasons for referral included medical management of a known connective tissue disease, question of inflammatory arthritis, and procedures. The demographics for new consults were as follows: 94% women, 45% Hispanic, and 80% between ages 60 and 101 years. Thirty-nine percent of patients had rheumatoid arthritis. Treatment interventions included addition of a disease-modifying antirheumatic drug in 11 patients, 11 procedures, nonpharmacologic management in 8 patients, and a change in the dose of the existing medication in 5 patients. At the initial evaluation, the average RAPID3 scores for patients reflected high severity of disease. CONCLUSION: The number of consults and the severity of disease seen highlight the importance of a rheumatologist's role in the community, especially because the number of homebound patients will dramatically increase in the future.
21425247 Efficacy and safety of vaccination against pandemic 2009 influenza A (H1N1) virus among pa 2011 Jul OBJECTIVE: To assess the efficacy and safety of vaccination against pandemic H1N1 virus in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) compared with healthy controls. METHODS: The study population comprised 41 RA patients, 21 SLE patients, 17 PsA patients, 15 AS patients, and 25 healthy controls. All were vaccinated using the Novartis MF59-adjuvanted H1N1v monovalent influenza vaccine. The immunogenicity of the vaccine was assessed on day 1 and again 4 weeks later by hemagglutination inhibition assay. Geometric mean titers and seroconversion rates were calculated for each group. The safety of the vaccine was evaluated using the 28-joint Disease Activity Score (DAS28) for RA and PsA, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: The proportion of baseline protective levels of antibodies against H1N1 was similar in all but the AS group, in which it was lower. The geometric mean titers increased significantly in all 5 groups. A substantial proportion of patients and controls responded to the vaccine. The healthy controls demonstrated a better response than each of the other groups: 84% versus 56% for RA, 67% for SLE, 59% for PsA, and 53% for AS. Multivariate logistic regression analysis identified RA and PsA as parameters of significantly lower response. The DAS28, BASDAI, and SLEDAI remained unchanged after vaccination. CONCLUSION: Vaccination against pandemic H1N1 using an adjuvanted H1N1v monovalent influenza is safe and induced an appropriate response in patients with RA, SLE, PsA, and AS.
22554167 Role overload, pain and physical dysfunction in early rheumatoid or undifferentiated infla 2012 May 3 BACKGROUND: Inflammatory arthritis impairs participation in societal roles. Role overload arises when the demands by a given role set exceed the resources; time and energy, to carry out the required tasks. The present study examines the association between role overload and disease outcomes in early inflammatory arthritis (EIA). METHODS: Patients (n = 104) of 7.61 months mean duration of inflammatory arthritis completed self-report questionnaires on sociodemographics, disease characteristics and role overload. Pain was assessed using the Short Form McGill Pain Questionnaire (MPQ) and physical functioning was measured with the Medical Outcomes Study Short Form 36 (SF-36) physical functioning score. Role overload was measured by the Role Overload Scale. Patients indicated the number of social roles they occupied from a total of the three typical roles; marital, parental and paid work. RESULTS: Participants' mean age was 56 years and 70.2% were female. Role overload was not correlated to the number of social roles, however, it was positively associated with pain (p = 0.004) and negatively associated with physical functioning (p = 0.001). On multivariate analysis, role overload was negatively associated with physical functioning after controlling for the relevant sociodemographic variables. CONCLUSION: This study identifies a possible reciprocal relationship between role overload and physical functioning in patients with EIA.