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ID PMID Title PublicationDate abstract
25232530 Rheumatoid arthritis susceptibility genes: An overview. 2014 Sep 18 Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes have been indicated so far in the pathogenesis of RA. Apart from human leukocyte antigen, large genome wide association studies have identified many loci involved in RA pathogenesis. These genes include protein tyrosine phosphatase, nonreceptor type 22, Peptidyl Arginine Deiminase type IV, signal transducer and activator of transcription 4, cytotoxic T-lymphocyte-associated protein 4, tumor necrosis factor-receptor associated factor 1/complement component 5, tumor necrosis factor and others. It is important to determine whether a combination of RA risk alleles are able to identify patients who will develop certain clinical outcomes, such myocardium infarction, severe infection or lymphoma, as well as to identify patients who will respond to biological medication therapy.
25332592 Acquired pure red cell aplasia in a patient of rheumatoid arthritis. 2014 Sep Pure red cell aplasia (PRCA) is characterized as a normocytic anemia associated with reticulocytopenia and the absence of erythroblasts in the bone marrow. PRCA can be induced by various causes such as thymoma, connective tissue disease, viral infection, lymphoma, and adverse drug reactions. There have been only a few reports of PRCA associated with rheumatoid arthritis (RA). We report a 45 year old female presented with symptomatic anemia of several months duration on a background of long standing seropositive deforming RA. Bone marrow examination revealed marked suppression of erythroid precursors with normal myeloid and megakaryocytic series, thereby confirming PRCA. Anemia improved following therapy with prednisolone 1 mg/kg/day. This article also reviews the current status of therapy in acquired PRCA.
24474949 Emerging role of endosomal toll-like receptors in rheumatoid arthritis. 2014 Toll-like receptors (TLRs) and their downstream signaling pathways have been comprehensively characterized in innate immunity. In addition to this function, these receptors have also been suggested to be involved in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Murine in vivo models and human in vitro tissue models of RA have provided a wealth of information on the potential activity of TLRs and components of the downstream signaling pathways. Whilst most early work investigated the cell surface TLRs, more recently the focus has moved to the endosomal TLRs 3, 7, 8, and 9. These receptors recognize self and foreign double-stranded RNA and single-stranded RNA and DNA. The development of therapeutics to inhibit the endosomal TLRs or components of their signaling cascades may represent a way to target inflammation upstream of cytokine production. This may allow for greater specificity than existing therapies including cytokine blockade. Here, we review the current information suggesting a role for the endosomal TLRs in RA pathogenesis and the efforts to target these receptors therapeutically.
32261488 A rheumatoid arthritis magnetic resonance imaging contrast agent based on folic acid conju 2014 May 21 Superparamagnetic iron oxide nanoparticles (SPIONs) offer unique properties for magnetic resonance imaging (MRI). Targeting imaging of rheumatoid arthritis in vivo requires a specific, magnetic sensitive and ultra-stable MRI contrast agent. In this study, SPIONs with a preferable colloid stability and optimized size were obtained by using an in situ polyol method with the diblock copolymer PEG-b-PAA acting as a surface ligand. Increasing the degree of polymerization (DP) of PAA from 18 to 36 to 57 led to the decreasing size of the iron oxide nanoparticles from 52 nm to 17 nm to 9 nm, respectively. Folic acid was conjugated onto PEG-PAA(x)@SPION as a specific targeting molecule for activated macrophages in a rheumatoid arthritis joint. To evaluate the stability and magnetic properties of the particle, a series of tests were conducted to evaluate and optimize the nanoparticles. In vitro endocytosis experiments confirmed the better performance of the folic acid conjugated SPIONs than the non-folic acid modified SPIONs. In vivo MRI clearly demonstrated the significant signal diminishment of the arthritis joint in antigen induced arthritis (AIA) rats by intravenous injection of the optimized nanoparticles FA-PEG-b-PAA(36)@SPION. These results indicated that FA-PEG-b-PAA(36)@SPION could serve as a promising candidate for the MRI of rheumatoid arthritis.
23902799 Cross-linking of IgGs bound on circulating neutrophils leads to an activation of endotheli 2013 Jul 31 BACKGROUND: Rheumatoid arthritis is characterized by the presence of circulating auto-antibodies, including rheumatoid factors, which recognize the Fc portion of IgGs. The neutrophil is the most abundant circulating leukocyte and it expresses high levels of FcγRs on its surface. The aim of the present study was to examine the capacity of circulating human neutrophils to be activated by rheumatoid factors and the consequences of these events on endothelium. METHODS: Neutrophil-bound IgGs were cross-linked with anti-human IgGs to mimick the presence of circulating rheumatoid factors and FcγRs-dependent signalling events and functions were examined. The IgG and IgM composition of rheumatoid factors isolated from the serum of RA patients was characterized. Adhesion of neutrophils to endothelial cells was quantified in response to the addition of rheumatoid factors. RESULTS: Cross-linking of IgGs bound on neutrophils leads to FcγRs-dependent tyrosine phosphorylation, mobilisation of intracellular calcium and the extracellular release of superoxide anions and lysozyme. Incubation of endothelial cells with the supernatant of activated neutrophils increases ICAM-1 expression and IL-8 production by endothelial cells. Finally, rheumatoid factors enhance neutrophil adhesion to endothelial cells. CONCLUSIONS: Our results show that activation of neutrophils' FcγRs by rheumatoid factors could participate in rheumatoid arthritis-associated vascular damage.
24009937 Depicting and comparing the time to normalize "erythrocyte sedimentation rate" following t 2013 Winter BACKGROUND: Erythrocyte sedimentation rate (ESR) is one of the predictors of improvement in handling rheumatoid arthritis. This study was designed to define and compare the time of achieving normal ESR and also the percentage for the normalization of this marker at several points of time in two different combination therapies. METHODS: Fifty-two rheumatoid arthritis patients randomly received methotrexate, chloroquine, prednisolone (MCP) or azathioprine, chloroquine, prednisolone (ACP) and all were followed up for 34 weeks. Chloroquine and azathioprine were given, 150 mg/d and 2 mg/kg/d, respectively. Methotrexate was given, 0.2 mg/kg/week and simultaneously increased 2.5 mg monthly if no clinical response was seen. Prednisolone was started, 0.3 mg/kg/d and tapered after one week. ESR at baseline and during follow-up were checked. The data were collected and analyzed. This clinical trial was registered in the Iranian Registry of Clinical Trials (www.irct.ir) with registration number ID: 2012110611383N1. RESULTS: The percentages of obtaining normal ESR after 2nd, 4th, 6th, 8th, 18th, 34th weeks of follow up were 42.4%, 53.9%, 57.7%, 65.4%, 88.5%, 96.2% in the MCP group and 47.9%, 65.3%, 74%, 78.3%, 82.7%, 87% in the ACP group. The mean time of obtaining normal ESR was 9.15 (95%CI, 5.58 to 12.73) weeks in MCP group and 9.04 (4.04 to 14.05) weeks in the ACP group (p>0.05). CONCLUSION: The results show that the time to achieve normal ESR and percentage of its normalization were almost the same in both treated groups.
25435925 Therapy gloves for patients with rheumatoid arthritis: a review. 2014 Dec Rheumatoid arthritis is a chronic inflammatory disease that causes pain, joint stiffness and swelling leading to impaired hand function and difficulty with daily activities. Wearing therapy gloves has been recommended by occupational therapists as one of the alternative treatment methods for rheumatoid arthritis. This study aims to review the available literature on the effects of wearing therapy gloves on patients' hand function and symptoms as well as to discuss the attributes of gloves that might influence the glove performance. An electronic databases search of MEDLINE, Physiotherapy Evidence Database, Occupational Therapy Systematic Evaluation of Evidence, Wiley Online Library, ScienceDirect and Cochrane Central Register of Controlled Trial was performed. Eight articles met the inclusion criteria, and covered seven clinical trials and one case study. Seven outcome measures were identified from the included studies and were then classified into two categories: hand function and hand symptoms. The hand symptoms such as pain, stiffness and swelling improve substantially when the therapy gloves are used. However, marginal or no improvement in hand function (with the exception of grip strength) linked to the use of therapy gloves is being reported. Further research is needed to quantify the effectiveness of therapy gloves, especially in improvement of hand function and in patients' interest in wearing therapy gloves. Furthermore, future studies should include parameters which might influence therapy gloves' performance, such as duration of trials, interface pressure generated by the gloves on the underlying skin and tissue, glove fit and construction, as well as thermophysiological comfort.
22083614 Bamboo nodes associated with mixed connective tissue disease as a cause of hoarseness. 2013 Mar Vocal fold lesions related to autoimmune diseases are rheumatoid nodules and, to a lesser extent, bamboo nodes. Mostly transverse, they are located in the middle third of the vocal cord and exhibit a yellowish appearance. The characteristic shape of these lesions led to their name. These vocal fold deposits may interfere with the normal vibratory cycle during phonation and thus may be an unusual cause of hoarseness. We present a 43-year-old woman with known mixed connective tissue disease and a dysphonia. Laryngostroboscopy showed bamboo nodes as described above. We applied several laryngeal injections of cortisone as described previously in the literature. Since this treatment did not lead to a sufficient voice improvement, we attempted to surgically remove the deposits. After the surgery, the voice improved considerably. In all patients with rheumatic diseases who suffer from a rough, breathy, or unstable voice, a laryngostroboscopic examination should be done. If, however, a bamboo node lesion of the vocal folds is found by the laryngologists, an associated autoimmune disorder must be assumed, and adequate diagnostic procedures have to be initiated. Local laryngeal injections (1-3 times) with steroids should be the first line of therapy. In unsuccessful cases, subsequent surgery can be a useful treatment of bamboo nodes to stabilize and improve voice quality.
23348732 iRHOM2 takes control of rheumatoid arthritis. 2013 Feb The cytokine TNF-α is a major drug target for rheumatoid arthritis, an inflammatory joint disorder. An alternative approach is to target the protease TNF-α convertase (TACE), which releases TNF-α from cells. However, because TACE cleaves other proteins involved in development and cancer, a tissue-specific inhibition of TACE in immune cells appears mandatory. In this issue of the JCI, Issuree et al. report that iRHOM2 is a TACE activator in immune cells. Loss of iRHOM2 largely protects mice from inflammatory arthritis, making iRHOM2 a potential drug target for this condition.
24619558 Intracellular Signaling Pathways in Rheumatoid Arthritis. 2013 Aug 19 Dysfunctional intracellular signaling involving deregulated activation of the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) and "cross-talk" between JAK/STAT and the stress-activated protein kinase/mitogen-activated protein kinase (SAPK/MAPK) and Phosphatidylinositide-3-Kinase/AKT/mammalian Target of Rapamycin (PI-3K/AKT/mTOR) pathways play a critical role in rheumatoid arthritis. This is exemplified by immune-mediated chronic inflammation, up-regulated matrix metalloproteinase gene expression, induction of articular chondrocyte apoptosis and "apoptosis-resistance" in rheumatoid synovial tissue. An important consideration in the development of novel therapeutics for rheumatoid arthritis will be the extent to which inhibiting these signal transduction pathways will sufficiently suppress immune cell-mediated inflammation to produce a lasting clinical remission and halt the progression of rheumatoid arthritis pathology. In that regard, the majority of the evidence accumulated over the past decade indicated that merely suppressing pro-inflammatory cytokine-mediated JAK/ STAT, SAPK/MAPK or PI-3K/AKT/mTOR activation in RA patients may be necessary but not sufficient to result in clinical improvement. Thus, targeting aberrant enzyme activities of spleen tyrosine kinase, sphingosine kinases-1, -2, transforming growth factor β-activated kinase-1, bone marrow kinase, and nuclear factor-κB-inducing kinase for intervention may also have to be considered.
23534697 Pain experiences and self-management strategies among middle-aged and older adults with ar 2013 Jul AIMS AND OBJECTIVES: The purposes were (1) to explore pain experiences and the use and perceived effectiveness of pain self-management methods among middle-aged and older adults with osteoarthritis or rheumatoid arthritis in mainland China and (2) to compare those with diagnoses of osteoarthritis and rheumatoid arthritis. BACKGROUND: Prior research has suggested that pain is a major concern for people with arthritis. However, studies systematically investigating pain experiences and self-management status of arthritis patients are scarce in mainland China. DESIGN: Descriptive survey. METHODS: Participants (n = 197) aged 45 and over, diagnosed with either osteoarthritis or rheumatoid arthritis, and experiencing persistent pain were administered three self-report questionnaires: the Demographic Data Questionnaire, the Brief Pain Inventory and the Pain Management Inventory. RESULTS: The mean of the overall pain intensity was 5.6 (SD = 1.3). The median of number of pain sites was 7.0 (QR = 7.0) and the overall pain interference was 6.0 (QR = 2.6). Most participants experienced moderate to severe pain and interference. The current methods used for managing pain were perceived as only moderately effective. The sample used a median of 4.0 (QR = 3.0) self-management methods. Most often used were prescribed medicine, massage, heat and activity pacing. Methods perceived as most helpful included prescribed medicine, over-the-counter medicine, hot baths and heat. Persons with rheumatoid arthritis had significantly more pain sites, higher pain intensity and greater number of pain management methods used compared to those with osteoarthritis. CONCLUSIONS: Pain management is a significant problem in this population. The findings highlight the importance of helping the individual to identify and appropriately use a variety of self-management methods, selecting the appropriate method(s) at any one time. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers are urged to develop appropriate interventions on pain management tailored to arthritis patients in mainland China.
24896807 Kre-Celazine(®) as a viable treatment for juvenile rheumatoid arthritis/juvenile idiopath 2014 Sep The purpose of this study was to ascertain whether an oral, non-prescription, nutritional supplement compound composed of a proprietary alkali-buffered creatine monohydrate and cetylated fatty acids mixture (Kre-Celazine(®)) was efficacious in reducing or eliminating refractory pain and inflammation, without untoward effects, in Juvenile Rheumatoid Arthritis (JRA), which is also called Juvenile Idiopathic Arthritis (JIA). JRA/JIA is a patho-physiologically complex, chronic childhood autoimmune inflammatory disease of unknown etiology. Numerous studies have unsuccessfully attempted to pinpoint a possible common initiation event. Officially considered an affliction of children below the age of 16 years, an initial diagnosis has been confirmed in infants less than 1 year old, to individuals older then 17 years. In this study, sixteen juveniles, ages 7 through 16 years, experiencing long-standing, unremitting pain and inflammation despite previous use of prescription anti-inflammatory drugs and NSAIDs, were enrolled in a 30-day, open-label clinical study and treated with Kre-Celazine. Efficacy of this nutritional supplement was determined by the juvenile's personal physician and based on observations of the following: (1) significant reduction or elimination of palpable signs of inflammation; (2) renormalization of range of motion; (3) reduction or absence of perceived pain as reported to the physician by the patient; (4) renormalization of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values. In addition, the individual's previous steroid or non-steroidal anti-inflamatory medication(s) were reduced or eliminated in a stepwise progressive fashion during the study.
23664285 [Cardio-respiratory involvement in adult-onset Still's disease]. 2013 Apr Cardiopulmonary involvement in adult-onset Still's disease is not as common as cutaneous and articular involvement. Pleuropericarditis is the most frequent thoracic manifestation. Although difficult, diagnosis of other thoracic manifestations, which may reveal the disease, is crucial, due to the high risk to life and the efficacy of new immunosuppressive agents. The pathophysiology involves essentially immunological factors, Still's disease being increasingly seen as an autoimmune inflammatory disease. Pro-inflammatory cytokines such as interleukine (IL) 1, 6 and 18 play a crucial role in macrophage activation, which is central in the pathophysiology of adult Still's disease. The classification of cardiopulmonary manifestations is based on anatomy. Cardiac lesions may involve all the tissues of the heart and the pulmonary arteries. Respiratory lesions may involve the pleura, the lung parenchyma (organizing pneumonitis, infiltrative lung disease, alveolar damage, amyloidosis), and the respiratory muscles, including the diaphragm. Finally, some manifestations may be provoked by the treatment itself. Steroids, the first-line treatment, are very effective in pleuropericarditis. Methotrexate used to be prescribed when steroids failed, but biotherapies such as IL1 and IL6 inhibitors have transformed the prognosis of forms resistant to these drugs.
24016270 A neutralization scFv antibody against IL-1β isolated from a NIPA-based bacterial display 2013 OBJECTIVE: RA is one of autoimmune diseases, has drawn great attention of the world. Currently, the anti- IL-1β monoclonal antibody Canakinumab (ACZ885) for treatment of RA has entered into clinical trials. However, Full length antibody has large molecular weight, and is difficult to penetrate the tissue or the nidus. In contrast, scFv has low molecular weight and strong penetration ability, and is favorable to increase the drug concentration in the indus, hence improving the efficacy of the drug. The aim of this study is to obtain a neutralizing scFv antibody from a combinatorial scFv library against hIL-1β by the modified NLPA-based bacterial display system, for further development of the small molecule antibody drug for treatment of RA. METHODS: The modified NIPA-based bacterial display system was used to construct the combinatorial scFv library derived from the spleen cDNA of immunized mice with hIL-1β. FACS was used to screen hIL- 1β-binding clones with FITC-labeled hIL-1β protein. Three clones were randomly selected from the third round of screening, and their nucleotide sequences were aligned with mouse immunoglobulin genes. The single chain antibody genes of the hIL-1β-binding clones were subcloned into the prokaryotic expression vector pET-27b for expression. The molecular mass of the purified anti-hIL-1β single chain antibody was about 28ku. The hIL-1β-binding ability of antibody were examined by ELISA and Western blot assays. Ability of the scFv antibody to neutralize hIL-1β was evaluated by the MTT test. CONCLUSIONS: In this study, it is the first time to use the NIPA-based bacteria display system to construct and screen the combinatorial scFv library. Three scFvs against hIL-1β were obtained from the scFv library of the immunized mice. Prokaryotically expressed and purified scFvs demonstrate binding ability with hIL-1β. Among the three clones. The MTT test suggests that scFv-20 is a neutralization antibody against hIL-1β. The study provides a lead candidate for further development of small molecule therapeutic antibodies for treatment of RA.
25694899 Instrumented reduction of a fixed C1-2 subluxation using occipital and C2/C3 fixation: A c 2013 BACKGROUND: Different strategies exist for reduction of the cervical spine. Placement of C1 lateral mass screws is a powerful technique but may be impossible in a degenerative or revision setting. We report the open, posterior-only, and instrumented reduction of a fixed C1-2 subluxation using occipital and C2/C3 fixation. The patient had rheumatoid arthritis and had undergone previous surgery of the cervical spine. METHODS: We performed a retrospective chart review and focused appraisal of the literature. RESULTS: Satisfactory reduction was achieved with this infrequently reported technique. CONCLUSIONS/LEVEL OF EVIDENCE: Spine surgeons may consider the described procedure a viable treatment alternative in problematic subluxations of the cervical spine. Level V.
25405094 Inhibition of rheumatoid arthritis by blocking connective tissue growth factor. 2014 Nov 18 The pathogenesis of rheumatoid arthritis (RA) remains to be completely elucidated so far; however, it is known that proinflammatory cytokines play a pivotal role in the induction of RA. Tumor necrosis factor (TNF-α), in particular, is considered to play a central role in bone destruction by mediating the abnormal activation of osteoclasts or the production of proteolytic enzymes through direct or indirect mechanisms. The use of TNF-α blocking agents has a significant impact on RA therapy. Anti-TNF-α blocking agents such as infliximab are very effective for treatment of RA, especially for the prevention of articular destruction. We have previously shown that several proteins exhibited extensive changes in their expression after amelioration of RA with infliximab treatment. Among the proteins, connective tissue growth factor (CTGF) has a significant role for the development of RA. Herein, we review the function of CTGF in the pathogenesis of RA and discuss the possibility of a novel treatment for RA. We propose that CTGF is a potentially novel effector molecule in the pathogenesis of RA. Blocking the CTGF pathways by biological agents may have great beneficial effect in patients with RA.
24678426 NF-κB and Rheumatoid Arthritis: Will Understanding Genetic Risk Lead to a Therapeutic Rew 2013 Apr 1 NF-κB has long been known to play an important role in autoimmune diseases such as rheumatoid arthritis (RA). Indeed, as our understanding of how NF-κB is utilized has increased, we have been hard put to find a process not associated with this transcription factor family in some way. However, new data originating, in part, from genome-wide association studies have demonstrated that very specific alterations in components of the NF-κB pathway are sufficient to confer increased risk of developing disease. Here we review the data which have identified specific components of the NF-κB pathway, and consider what is known of their mechanisms of action and how these mechanisms might play into the disease process. In addition, the use of genetic information to predict RA is considered.
23858345 Pyoderma gangrenosum of the breast treated with intravenous immunoglobulin. 2013 Jun 30 BACKGROUND: Pyoderma gangrenosum is a rare neutrophilic dermatosis which leads to necrotic and painful skin ulceration. PG of the breast is extremely rare with 32 documented cases in the current literature. Delay in diagnosis worsens scarring as the ulcers are rapidly expanding, painful and usually slow to heal. CASE PRESENTATION: We present a case of pyoderma gangrenosum of the breast in a patient with associated rheumatoid arthritis which was initially diagnosed as an infected breast ulcer and later successfully treated with systemic steroids and intravenous immunoglobulin (IVIG). CONCLUSION: Even though PG of the breast has been gaining increased recognition over the past two decades, this has been more common in the post-surgical setting. This case highlights the need to consider PG as a differential diagnosis when faced with unsual cases of breast ulceration and the importance of multidisplinary approach for effective treatment of this condition.
23529572 The role of leukotrienes in immunopathogenesis of rheumatoid arthritis. 2013 Mar 26 Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints for which there is no strict cure. However, conventional medications can reduce inflammation, relieve pain, and slow joint damage. Leukotrienes are a family of paracrine agents derived from oxidative metabolism of arachidonic acid. Synthesis of lipid mediators and subsequent induction of receptor activity are tightly regulated under normal physiological conditions, so that enzyme and/or receptor dysfunction can lead to a variety of clinical signs and symptoms of disease, such as local pain and tissue edema. In these tissues, immunocompetent cells accumulate at the site of injury, contributing to tissue damage and perpetuation of the disease process. Leukotrienes (often leukotriene B4) as potent chemotactic agents can provoke most signs and symptoms in rheumatoid arthritis by initiating, coordinating, sustaining, and amplifying the inflammatory response, through recruitment of leukocytes. A number of studies have reported that pharmacological modulation in this field can significantly attenuate clinical manifestations associated with different inflammatory pathologies.
29539361 Erosive polyarthropathy in a Late Roman skeleton from northern France: A new case of rheum 2013 Mar A skeleton from the Late Roman period, recovered in Amiens, northern France, exhibits multiple symmetrical marginal erosions, primarily involving the metacarpophalangeal and metatarsophalangeal joints. Other skeletal changes include erosions of several peripheral joints and some entheses, and severe osteoporosis. Macroscopic and radiological aspects of the lesions, as well as the absence of spinal and sacroiliac joints involvement, are consistent with a diagnosis of rheumatoid arthritis. Differential diagnosis includes other erosive arthropathies, in particular the diseases belonging to the spondyloarthropathy group. This case provides a new evidence of the presence of rheumatoid arthritis in Western Europe long before the colonisation of the Americas by Europeans.