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

ID PMID Title PublicationDate abstract
25546349 Trikatu, a herbal compound mitigates the biochemical and immunological complications in ad 2017 Mar AIM: Rheumatoid arthritis is a chronic inflammatory autoimmune disorder with multi-factorial factors influencing disease alleviation in synovial joints. The aim of this study was to investigate the anti-arthritic efficacy of trikatu, a herbal compound, on biochemical and immunological complications in adjuvant-induced arthritic rats. METHODS: Arthritis was induced in rats by a single intradermal injection of complete Freund's adjuvant (0.1 mL) into the foot pad of the right hind paw. Trikatu (1000 mg/kg body weight, oral) and indomethacin (3 mg/kg body weight, intrap intraperitoneal) were administered for 8 days from days 11 to 18 after adjuvant injection. RESULTS: Our present study results evidenced a significant alteration in the activities/levels of lysosomal enzymes, protein bound carbohydrates, bone collagen, urinary constituents like hydroxyproline and total glycosaminoglycans, lipid peroxidation, antioxidant status, lipid profiles, rheumatoid factor and inflammatory mediators in adjuvant-induced arthritic rats. Trikatu treatment (1000 mg/kg/body weight) reverted back all the above biochemical and immunological parameters to near normal levels in arthritic rats as evidenced by the radiological and histopathological assessements . CONCLUSION: These results suggest that trikatu could be a promising alternative drug for the control and management of rheumatoid arthritis.
25035832 Advances in the treatment of cervical rheumatoid: Less surgery and less morbidity. 2014 Jul 18 Rheumatoid arthritis is a chronic systemic inflammatory disease that often affects the cervical spine. While it was initially thought that cervical involvement was innocuous, natural history studies have substantiated the progressive nature of untreated disease. Over the past 50 years, there has been further elucidation in the pathophysiology of the disease, as well as significant advancements in medical and surgical therapy. The introduction of disease modifying drugs and biologic agents has reduced the amount of patients with advanced stages of the disease needing surgery. Advancement in instrumentation techniques has improved patient outcomes and fusion rates. The introduction of endoscopic approaches for ventral decompression may further lower surgical morbidity. In this review, we give a brief overview of the pertinent positives of the disease. A discussion of historical techniques and the evolution of surgical therapy into the modern era is provided. With improved medical therapies and less invasive approaches, we will likely continue to see less advanced cases of disease and less surgical morbidity. Nonetheless, a thorough understanding of the disease is crucial, as its systemic involvement and need for continued medical therapy have tremendous impact on overall complications and outcomes even in patients being seen for standard degenerative disease with comorbid rheumatoid.
24083931 Fever acquired overseas is not always infectious in etiology: adult-onset Still's disease 2013 Oct Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology characterized by spiking fever, arthritis or arthralgia, rash, and leukocytosis. The nonspecific findings and epidemiology of the disease can complicate the diagnosis among deployed U.S. personnel, because they are exposed to infectious etiologies that can present in a similar fashion. We present a case of 19-year-old U.S. Army soldier who was deployed to Afghanistan and eventually medevaced to Walter Reed National Military Medical Center complaining of arthralgia, diffuse myalgia, daily spiking fever, and laboratory abnormalities including leukocytosis and elevated liver-associated enzymes. After an initial concern for an infectious etiology, the patient met Yamaguchi criteria for the diagnosis for AOSD. The patient's clinical course, pertinent laboratory, and pathology data are reviewed in the context of approaching the diagnosis and treatment of AOSD. This case highlights that providers need to maintain a high clinical suspicion for less common conditions such as AOSD in the setting of unresolving nonspecific findings such as fever, rash, and leukocytosis.
25071309 Reduction of IL-20 Expression in Rheumatoid Arthritis by Linear Polarized Infrared Light I 2014 Jul 1 BACKGROUND: Low-level laser is being evaluated for treating rheumatoid arthritis (RA). Recently, the linear polarized infrared light (Super Lizer, SL) irradiation may also be useful for RA treatment. However, the molecular mechanism underlying the effectiveness of SL on RA is unclear. It has been IL-20 may involved in RA disease progression. AIM: To understand how SL action, we constructed the experimental model in vitro using human rheumatoid fibroblast-like synoviocyte (MH7A) and collagen induced (CIA) RA rat in vivo. We examined the effect of SL irradiation on IL-20 gene expression in MH7A and IL-20 protein production in CIA) rat joints. MATERIALS AND METHODS: MH7A was cultured and challenged with IL-1ß, then examined IL-20 and IL-20R mRNA level by DNA microarray. IL-20 protein expression was examined by immunohistochemistry using a specific antibody against rat IL-20. RESULT: Scatter plot analysis demonstrated that an increase in IL-20 gene expression by IL-1ß was reduced by SL irradiation, but IL-20R did not show a significant change. The Immunohistochemical analysis demonstrated a strong IL-20 staining in synovial membrane tissue of CIA rat joint, and SL irradiation significantly reduced the staining. DISCUSSION: Since IL-20 has been identified as an important cytokine in the pathogenesis of RA, the reduction of IL-20 expression by SL irradiation may be one of mechanisms in reduction of inflammation in RA joints by SL irradiation suggesting that SL irradiation may be useful for RA therapy.
25035833 Inflammation, lipid metabolism and cardiovascular risk in rheumatoid arthritis: A qualitat 2014 Jul 18 Life expectancy in patients with rheumatoid arthritis (RA) is reduced compared to the general population owing to an increase in cardiovascular diseases (CVD) not fully explained by traditional cardiovascular risk factors. In recent years, interest has been focused on the alterations in lipid metabolism in relation to chronic inflammation as one of the possible mechanisms involved in the pathogenesis of atherosclerosis of RA patients. Research regarding this issue has revealed quantitative alterations in lipoproteins during the acute-phase reaction, and has also demonstrated structural alterations in these lipoproteins which affect their functional abilities. Although many alterations in lipid metabolism have been described in this regard, these structural changes associated with inflammation are particularly important in high-density lipoproteins as they affect their cardioprotective functions. In this respect, excessive oxidation in low-density lipoprotein (LDL) and increased lipoprotein(a) with a predominance of smaller apolipoprotein(a) isoforms has also been reported. This article will discuss proinflammatory high-density lipoproteins (piHDL), oxidized LDL and lipoprotein(a). Elevated concentrations of these lipoproteins with marked pro-atherogenic properties have been observed in RA patients, which could help to explain the increased cardiovascular risk of these patients.
25152867 Utilizing regulatory T cells against rheumatoid arthritis. 2014 Regulatory T (Treg) cells are essential for normal immune surveillance systems, and their dysfunction leads to development of diseases, such as autoimmune disorders. CD4(+)CD25(+) Treg cells are well-known suppressive cells, which express the transcription factor Foxp3, are indispensable for the maintenance of immune self-tolerance and homeostasis by suppressing aberrant or excessive immune response. Other Foxp3(-) Treg cells include Tr1, Th3, CD8(+)CD28(-/-), and Qa1-restricted T cells; however, the contribution of these Treg cells to self-tolerance, immune homeostasis as well as preventing autoimmunity is not well defined. Here, we discuss the phenotypes and function of Foxp3(+) Treg cells and the potential use of such Treg cells against rheumatoid arthritis (RA). Of note, even though most expanded populations of Foxp3(+) Treg cells exhibit suppressive activity, tissue-associated or antigen-specific Treg cells appear superior in suppressing local autoimmune disorders such as RA. In addition, utilizing tissue-associated Foxp3(+) Treg cells from stem cells may stable Foxp3 expression and avoid induction of a potentially detrimental systemic immunosuppression.
24926358 Inhibitory effect of sodium houttuyfonate on synovial proliferation in vitro in cells from 2014 Jun The aim of the present study was to investigate the inhibitory effect of sodium houttuyfonate (SH) on synovial cell proliferation in vitro. Primary cells were obtained from the synovial tissue of a patient with rheumatoid arthritis (RA). The cells were divided into five treatment groups as follows: the control group (group 1), 25 μg/ml SH-treated group (group 2), 50 μg/ml SH-treated group (group 3), 100 μg/ml SH-treated group (group 4) and the 200 μg/ml SH-treated group (group 5). Following seven days of treatment, the proliferation rate of the synovial cells was then detected using an MTT assay. The expression level of proliferative synovial cells markedly decreased in the SH-treated groups in a dose-dependent manner compared with the control group. In conclusion, the present study demonstrated that SH was able to inhibit the proliferation of synovial cells obtained from a patient with RA. These results provide a potential theoretical basis for the development of a safe and effective treatment against RA in the future.
24365311 Neurologic complications of craniovertebral dislocation. 2014 Craniovertebral dislocation is uncommon, but its diagnosis is important taking into account the potential severity of the neurologic complications. A number of causes are known; the most common are Down syndrome, rheumatoid arthritis, Paget's disease, other metabolic bone diseases, and craniocervical trauma. Down's syndrome is a relatively common clinical condition but craniovertebral subluxation is only observed in a small percentage of patients. About half of all cervical spine injuries affect the atlanto-occipital region and C2 vertebra. In rheumatoid arthritis, craniocervical dislocation occurs in up to 40% of patients with severe disease. In Paget's disease, involvement of the craniovertebral region occurs in about 30% of all cases. The clinical neurologic syndrome is characterized by local pain, features of upper spinal cord and medullary compression, positive Lhermitte phenomenon, syncope associated with neck flexion, vertebral artery obstruction or dissection leading to stroke, and asymmetrical lower cranial nerve palsies. Neuroimaging is essential to confirm the clinical diagnosis and to categorize severity. The treatment of this disorder is usually surgical, but traction and external immobilization is relevant in some cases. Specific conditions may require additional treatments such as radiotherapy, antibiotics, or chemotherapy.
25378947 Use of the painDETECT tool in rheumatoid arthritis suggests neuropathic and sensitization 2014 Rheumatoid arthritis (RA) is an inflammatory autoimmune condition typified by systemic inflammation targeted toward synovial joints. Inhibition of proinflammatory networks by disease-modifying antirheumatic drugs, eg, methotrexate and biologic therapies, including tumor necrosis factor-α inhibitors, often leads to suppression of disease activity observed at the clinical level. However, despite the era of widespread use of disease-modifying treatments, there remain significant groups of patients who continue to experience pain. Our study formulated a pain assessment tool in the arthritis clinic to assess feasibility of measurements including the visual analog scale (VAS) and painDETECT to assess multimodal features of pain in people with established RA (n=100). Clinical measures of disease activity (Disease Activity Score in 28 Joints [DAS28]) were also recorded. Our data showed that despite the majority of subjects on at least one disease-modifying agent, the majority of patients reported severe pain (54%) by VAS, despite well-controlled clinical disease, with mean DAS28 2.07±0.9. Using the painDETECT questionnaire, 67% of patients had unlikely neuropathic pain. A significant proportion of subjects (28%) had possible neuropathic pain and 5% had features of likely neuropathic pain by painDETECT scoring. We found a positive correlation between VAS and painDETECT (R (2)=0.757). Of note, the group who had likely or probable neuropathic pain also showed significantly increased pain reporting by VAS (P<0.01). Subjects who were clinically obese (body mass index >30) also had statistically higher proportions of pain reporting (VAS 89.0±0.7 mm) compared with subjects who had a normal body mass index (VAS 45.2±21.8 mm), P<0.05. Our findings suggest that multimodal features of pain perception exist in RA, including neuropathic and sensitization elements, perhaps explaining why a subgroup of people with RA continue to experience ongoing pain, despite their apparent suppression of inflammation.
23737674 Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens. 2013 A statistically significant association between periodontal disease (PD) and systemic diseases has been identified. Rheumatoid arthritis (RA), which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species have been identified as periodontal pathogens, and these organisms are linked to various types of PD. The most analyzed species of periodontopathic bacteria are Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans. Antibodies and DNA from these oral pathogens have been isolated from the sera and synovial fluids of RA patients. This rapid communication describes the role of periodontal pathogens in the etiopathogenesis of RA.
26155116 Modulating effects of leflunomide on the balance of Th17/Treg cells in collageninduced art 2014 To evaluated the effect and mechanism of leflunomide (LEF) in murine model of collage-induced arthritis (CIA) on modulating the balance of Th17/Treg cells. DBA mice were divided into: control, CIA, CIA + LEF and CIA + Ibuprofen group. After 14 days immunization with bovine type II collagen (CII), except control group, mice were orally administered saline (CIA group), LEF or ibuprofen daily for 14 days. The severity of arthritis joint was assessed by using arthritis score. The numbers of CD3 + CD4 + interleukin 17 (IL-17) + Th17 cells and CD4 + CD25 + Foxp3+ Tregs were determined by flow cytometry, the expression of ROR-γt, Foxp3 and IL-21 mRNA in spleen were quantified by RT-PCR and IL-17, IL-21 and transforming growth factor β (TGF-β) level in serum was measured by ELISA. In comparison with CIA group, CIA + LEF and CIA + Ibuprofen group reduced the disease severity obviously (p < 0.05). Leflunomide reduced Th17 cells, the expression of ROR-γt and IL-21 mRNA (p < 0.05) and the levels of IL-17 and IL-21 in serum. In addition, Ibuprofen but not LEF has effect on Treg cells number, Foxp3 mRNA expression and TGF-β secretion. These results indicate that LEF effect on the balance od Th17/Treg through suppressing Th17 cells, but not stimulating Treg cells. Leflunomide may act as a potential immunomodulator for the treatment of rheumatoid arthritis (RA).
24839573 A case of rheumatoid arthritis and limited systemic sclerosis overlap successfully treated 2014 A 57-year-old woman with rheumatoid arthritis (RA) and limited systemic sclerosis (lSSc) was suspected to have lymphadenopathy and primary biliary cirrhosis (PBC). Lymph node biopsy showed reactive follicular lymphadenopathy with intrafollicular plasmacyte infiltration that was interleukin-6 positive by immunohistostaining. Because of gradually worsening arthritis, tocilizumab was administered and arthritis improved markedly. Interestingly, lymphadenopathy and PBC improved simultaneously. This suggested that interleukin-6 might play an important role in reactive lymphadenopathy and PBC associated with RA/lSSc.
25202442 25(OH) vitamin D serum values and rheumatoid arthritis disease activity (DA S28 ESR). 2014 Summer BACKGROUND: The role of vitamin D in the pathogenesis of rheumatoid arthritis is under investigation. This study was designed to evaluate the correlation between serum values of 25(OH) vitamin D [25(OH)D] and disease activity in rheumatoid arthritis (RA) patients according to Disease Activity Score 28 joints and ESR (DA S28 ESR). METHODS: Ninety-nine patients according to ACR classification criteria for RA and 68 healthy controls were included in this study. The participants with known confounding risk factors affecting serum values of 25(OH)D were excluded. All patients were under treatment with supplementary calcium carbonate (1500mg), 25(OH)D (800U), and Hydroxychloroquine (6mg/kg). The control group was mostly recruited from patients' relatives who lived with them to minimize the impact of diverse lifestyles on 25(OH)D status. Disease activity was assessed by DA S28 ESR. Serum concentrations of 25(OH)D were measured. Serum values of 25(OH)D less than 50 nmol/L were considered 25(OH)D deficiency. RESULTS: The mean 25(OH)D serum values were 83.74±46.45 nmol/L in patients and 46.53±34.07 nmol/L in controls. After adjustment for age, sex and BMI, multivariate analysis showed no correlation between 25(OH)D serum levels and DAS in RA (P=0.29, rp=0.11). However, 25(OH)D serum values were significantly lower in patients with early diagnosed RA compared with the other patients (p=0.012). In the early diagnosed patients, 25(OH)D and anti-CCP serum values were negatively correlated (P=0.04, rs=-0.5). CONCLUSION: This study showed that there was no correlation between 25(OH)D serum values and DAS over a short duration of disease course. However, in early RA, 25(OH) D serum values were lower than the established RA.
24173233 Exposure to mimivirus collagen promotes arthritis. 2014 Jan Collagens, the most abundant proteins in animals, also occur in some recently described nucleocytoplasmic large DNA viruses such as Mimiviridae, which replicate in amoebae. To clarify the impact of viral collagens on the immune response of animals exposed to Mimiviridae, we have investigated the localization of collagens in Acanthamoeba polyphaga mimivirus particles and the response of mice to immunization with mimivirus particles. Using protein biotinylation, we have first shown that viral collagen encoded by open reading frame L71 is present at the surface of mimivirus particles. Exposure to mimivirus collagens elicited the production of anti-collagen antibodies in DBA/1 mice immunized intradermally with mimivirus protein extracts. This antibody response also targeted mouse collagen type II and was accompanied by T-cell reactivity to collagen and joint inflammation, as observed in collagen-induced arthritis following immunization of mice with bovine collagen type II. The broad distribution of nucleocytoplasmic large DNA viruses in the environment suggests that humans are constantly exposed to such large virus particles. A survey of blood sera from healthy human subjects and from rheumatoid arthritis patients indeed demonstrated that 30% of healthy-subject and 36% of rheumatoid arthritis sera recognized the major mimivirus capsid protein L425. Moreover, whereas 6% of healthy-subject sera recognized the mimivirus collagen protein L71, 22% of rheumatoid arthritis sera were positive for mimivirus L71. Accordingly, our study shows that environmental exposure to mimivirus represents a risk factor in triggering autoimmunity to collagens.
25225527 Effects of B-lymphocyte dysfunction on the serum copper, selenium and zinc levels of rheum 2014 Sep OBJECTIVE: To study the effects of B-lymphocyte dysfunction on the serum copper, selenium and zinc levels of rheumatoid arthritis (RA) patients, and to provide evidence for clinical practice. METHODS: Sixty RA patients enrolled in our hospital from August 2009 to August 2013 were selected as the observation group. Another 60 healthy subjects who received physical examinations in our hospital were selected as the control group. Their B-lymphocyte stimulator (BlyS) levels and CD19(+)CD25(+) lymphocyte percentages were determined. The levels of trace elements were measured, and correlation analysis was performed. RESULTS: The BlyS levels of the observation group and the control group were (0.39±0.21) ng/ml and (0.13±0.04) ng/ml respectively, which were significantly different (P<0.05). The percentages of CD25(+), CD19(+) and CD19(+)CD25(+) lymphocytes in the observation group were significantly higher than those in the control group (P<0.05). The serum copper, selenium and zinc levels of the observation group were significantly lower than those of the control group (P<0.05). Pearson's correlation analysis showed that the BlyS level was correlated with the levels of copper, selenium and zinc respectively (r=-0.541, -0.370, -0.430, P<0.05). CONCLUSION: Rheumatoid Arthritis may be induced by BlyS-mediated B-lymphocyte dysplasia and dysfunction, accompanied by decreased expressions of copper, selenium and zinc.
24967065 Matrix-mini-tablets of lornoxicam for targeting early morning peak symptoms of rheumatoid 2014 May OBJECTIVES: The aim of present research was to develop matrix-mini-tablets of lornoxicam filled in capsule for targeting early morning peak symptoms of rheumatoid arthritis. MATERIALS AND METHODS: Matrix-mini-tablets of lornoxicam were prepared by direct compression method using microsomal enzyme dependent and pH-sensitive polymers which were further filled into an empty HPMC capsule. To assess the compatibility, FT-IR and DSC studies for pure drug, polymers and their physical mixture were performed. The formulated batches were subjected to physicochemical studies, estimation of drug content, in vitro drug release, drug release kinetics, and stability studies. RESULTS: When FTIR and DSC studies were performed it was found that there was no interaction between lornoxicam and polymers which used. All the physicochemical properties of prepared matrix-mini-tablets were found to be in normal limits. The percentage of drug content was found to be 99.60±0.07%. Our optimized matrix mini-tablets-filled-capsule formulation F30 released lornoxicam after a lag time of 5.02±0.92 hr, 95.48±0.65 % at the end of 8 hr and 99.90±0.83 % at the end of 12 hr. Stability was also found for this formulation as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. CONCLUSION: A novel colon targeted delivery system of lornoxicam was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis.
24287190 Diagnosis of Sjögren's syndrome: American-European and the American College of Rheumatolo 2014 Feb Classification criteria provide a formalized approach to studying course and management of rheumatic disease, as well as a measure of improvement in care. Understanding the purposes of classification criteria sets and the differences between different classification criteria is crucial for understanding rheumatic disease and for the design and conduct of clinical and epidemiologic investigations. In this article, the similarities and differences between the American-European Consensus Group Criteria (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome and the clinical implications of switching to the ACR classification criteria from the AECG are described.
24353626 Anti-cyclic citrullinated peptide antibody is a good indicator for the diagnosis of rheuma 2013 May OBJECTIVES: Anti-cyclic citrullinated peptide (CCP) antibody has recently been used in the classification of rheumatoid arthritis (RA). This antibody is more specific than rheumatoid factor (RF) for the diagnosis of RA. The study objectives were to determine the sensitivity, specificity, positive and negative predictive values of anti-CCP in RA diagnosis. METHODOLOGY: Eighty RA patients and 80 non-RA individuals were included in the study. Blood was collected from both arms of study subjects and tested for anti-CCP and RF antibodies. Relevant clinical information and laboratory profiles of the RA patients were evaluated using patients' medical records and Integrated Laboratory Management System (ILMS), respectively. Results : The sensitivity and specificity of anti-CCP were 35% and 100% respectively. The positive and negative predictive values were 100% and 61%, respectively. Positive anti-CCP was found significantly associated with multiple joint pain (p< 0.001) and hand's joints pain (p=0.01), symmetrical joints involvement (p=0.015) and high CRP value (p<0.001). Anti-CCP was also found to have positive association with RF (p<0.001). CONCLUSION: Anti-CCP is highly specific for the diagnosis of RA. High positive predictive value should be taken into consideration for effective treatment.
23372569 Killer cell immunoglobulin-like receptor gene associations with autoimmune and allergic di 2013 Killer cell immunoglobulin-like receptors (KIRs) are a family of cell surface inhibitory or activating receptors expressed on natural killer cells and some subpopulations of T lymphocytes. KIR genes are clustered in the 19q13.4 region and are characterized by both allelic (high numbers of variants) and haplotypic (different numbers of genes for inhibitory and activating receptors on individual chromosomes) polymorphism. This contributes to diverse susceptibility to diseases and other clinical situations. Associations of KIR genes, as well as of genes for their ligands, with selected diseases such as psoriasis vulgaris and atopic dermatitis, rheumatoid arthritis, recurrent spontaneous abortion, and non-small cell lung cancer are discussed in the context of NK and T cell functions.
23858344 Eruptive seborrheic keratoses associated with adalimumab use. 2013 Jun 30 BACKGROUND: Seborrheic keratoses are common, benign cutaneous growths, however in rare situations they can acutely erupt in large numbers. Eruptive seborrheic keratoses can be associated with internal malignancy (sign of Leser-Trelat), but may also appear in conjunction with inflammatory dermatoses and adverse drug reactions. MAIN OBSERVATION: A 71-year-old Caucasian man presented with acute onset of a pruritic, burning papular erythematous rash on his chest, upper extremities and lower extremities after a routine adalimumab injection for rheumatoid arthritis. Two skin biopsies obtained showed findings diagnostic of seborrheic keratoses. Spontaneous resolution of the diffuse eruptive seborrheic keratoses was achieved within 3 months of discontinuing adalimumab therapy. CONCLUSIONS: We believe the development of eruptive seborrheic keratoses due to adalimumab therapy is rare, and because our patient responded promptly to discontinuation of the drug we suggest this should be the preferred course of action in future cases.