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ID PMID Title PublicationDate abstract
22530144 Bedtime single-dose prednisolone in clinically stable rheumatoid arthritis patients. 2012 Introduction. Sign and symptoms of rheumatoid arthritis have circadian rhythms and are more prominent in the morning. Timing of glucocorticoid administration may be important with respect to the natural secretion of endogenous glucocorticoids. Herein, we intended to test the hypothesis that bedtime administration of prednisolone could be more efficient in controlling signs and symptoms in patients with RA. Material and Methods. Sixty patients with stable disease were treated with single dose prednisolone at 8 a.m. for the first three months and thereafter with similar dose at 10 PM for the next three months (before-after method). We compared fatigue scores, morning stiffness and pain scores, Clinical Disease Activity Indices, erythrocyte sedimentation rates, C Reactive Protein, and profile of adverse effects. Results. The mean of morning stiffness, fatigue scores, CRP and CDAI decreased statistically when prednisolone was administrated at 10 p.m. The means of pain scores and ESR were also decreased when the patients took prednisolone at night, without significant statistical difference. Conclusion. Administration of low-dose oral prednisolone could reduce disease activity scores in morning in clinically stable patients with RA. So it could be supposed that administrating bedtime prednisolone may permit the smallest possible dose.
22374445 [Regulation of inflammation through JAK3-Stat6 pathway in dendritic cells]. 2012 Dendritic cells (DCs) is the cell that act as source of the immune response by exquisitely presenting antigens to acquired immunity such as the T cells. Janus kinase (JAK) is a tyrosine kinase that is activated immediately after the cytokine binds to its unique receptor expressed on the cell surface. Among the JAKs, expression of JAK3 is limited on haematopoietic cells and is indispensable for lymphocyte development and proliferation. We have demonstrated that JAK3-deficient DCs normally develop, uptake antigens, produce inflammatory cytokines and function as an antigen-presenting cell, although they over-produce IL-10. Among the transcription factors that are known to be activated by JAK3, we explored the phenotype of Stat6-deficient DCs which is a transcription factor specifically activated by JAK3. Interestingly, development, function and inflammatory cytokine production was normal with over-production of IL-10 which was in line with the JAK3-deficient DCs. IL-4 is well known to activate JAK3-Stat6 in the cytoplasm and has been reported to be produced in the synovial fluid of rheumatoid arthritis patients. Hence the suppression of IL-10 production by IL-4 can be considered as one of the inflammatory process of arthritis. Moreover, induction of IL-10 production by DCs can be one mechanism of action of the JAK inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid arthritis in clinical trials.
21687505 Anti-inflammatory and immunomodulatory effects of paeonia lactiflora pall., a traditional 2011 In China, Korea, and Japan, a decoction of the dried root without bark of Paeonia lactiflora Pall. has been used in the treatment of rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms, and fever for more than 1200 years. A water/ethanol extract of the root is now known as total glucosides of peony (TGP), which contains more than 15 components. Paeoniflorin is the most abundant ingredient and accounts for the pharmacological effects observed with TGP in both in vitro and in vivo studies. The analgesic effect of TGP was confirmed in various animal models of pain, which may be mediated partly by adenosine A1 receptor. The direct anti-inflammatory effects of TGP were observed in animal models of both acute and subacute inflammation, by inhibiting the production of prostaglandin E2, leukotriene B4, and nitric oxide, and by suppressing the increase of intracellular calcium ion concentration. TGP was also reported to have protective effects of cells against oxidative stress. In vitro, dual effects of TGP were noted on the proliferation of lymphocytes, differentiation of Th/Ts lymphocytes, and the production of proinflammatory cytokines and antibodies. In vivo, TGP inhibited the delayed-type hypersensitivity in immuno-activated mice, and enhanced the delayed-type hypersensitivity in immuno-suppressed mice. In adjuvant arthritis rats, paeoniflorin exerted immunosuppressive effects. The beneficial effects of TGP in treating rheumatoid arthritis were verified by randomized controlled trials. The adverse events of TGP were mainly gastrointestinal tract disturbances, mostly mild diarrhea.
22242205 Use of clinical disease activity index score for assessment of disease activity in rheumat 2011 Introduction. Serial objective assessment of disease activity in Rheumatoid Arthritis (RA) is imperative to achieve remission. The CDAI score appears more practical than DAS-28 in routine assessment of disease activity in RA patients. Objective. To evaluate correlation and agreement of the DAS-28 with CDAI in RA patients. Methods. A total of 200 patients of RA were evaluated by DAS-28 and CDAI and divided into 4 categories of disease activity i.e. Group-I: Remission (DAS-28 < 2.6; CDAI < 2.8), Group II: Low disease activity (DAS-28 = 2.6-3.2; CDAI = 2.8-10), Group III: Moderate disease activity (DAS-28 = 3.2- 5.1; CDAI = 10-22), Group IV: High disease activity (DAS-28 > 5.1; CDAI > 22). DAS-28 was compared to CDAI in each group using spearman correlation coefficient and kappa statistics. Results. Group I shows mean DAS-28 of 1.99 ± 0.38; mean CDAI of 0.90 ± 0.65, (P = 0.0001). Group II shows mean DAS-28 of 3.04 ± 0.17; mean CDAI of 6.45 ± 02.35, (P = 0.0001). Group III shows mean DAS-28 of 4.25 ± 0.58; mean CDAI of 16.46 ± 3.31 (P < 0.0001). Group IV shows mean DAS-28 of 6.38 ± 0.87; mean CDAI of 38.56 ± 11.88 (P < 0.0001). Kappa statistics (κ) of the above comparison was 0.533. Conclusion. Our findings indicate that CDAI-a composite score that employs only clinical variables and omits assessment of Acute Phase Reactant (APR), has moderate to good correlation (Kappa value = 0.533) to DAS-28 for assessment of disease activity in RA patients.
21514322 Selective elimination of pathogenic synovial fluid T-cells from rheumatoid arthritis and j 2011 Aug 30 In Rheumatoid Arthritis (RA) and Juvenile Idiopathic Arthritis (JIA) elimination of autoreactive T-cells by FasL/Fas-mediated Activation-Induced Cell Death (AICD) appears to be inhibited resulting in the perpetuation of the inflammatory response and concomitant progressive tissue destruction. Here, we report on a novel strategy that aims to overcome the local inhibition of AICD by using rationally designed recombinant fusion proteins in which sFasL is genetically fused to a T-cell selective targeting domain. The series included sFasL fusion proteins with engineered binding specificity for various T-cell surface-expressed proteins including CD7, CD28, RANKL and CD40L. The proposed mode of action is that selective binding of a given sFasL fusion protein results in its accretion at the cell surface of T-cells only, displaying a surplus of sFasL that is available to reactivate AICD in pathogenic synovial T-cells. Of the series of T-cell targeting FasL fusion proteins a CD7-targeted fusion protein, designated scFvCD7:sFasL, proved to be the most potent, with significant pro-apoptotic activity towards synovial fluid T-cells in all patient samples tested (RA; n=22: JIA; n=6). Treatment with scFvCD7:sFasL induced up to 80% apoptosis in CD3-positive synovial T-cells. Importantly, scFvCD7:sFasL potently activated Fas-signaling in synovial T(H1)-cells as well as synovial T(reg) cells, but not in synovial T(H2) cells. These findings indicate that scFvCD7:sFasL may be of therapeutic value for the selective elimination of pathogenic synovial T-cells of the T(H1) subtype in both RA and JIA.
22021998 Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuva 2011 Sep OBJECTIVE: To evaluate the concomitant administration of methotrexate and curcumin for antiarthiritic activity in rats. MATERIALS AND METHODS: Arthritis was induced in rats following a single subplantar injection of Freund's complete adjuvant (0.1 ml). Rats were divided into six groups of six animals each. Group I and II were control injected with saline and Freund's complete adjuvant (0.1 ml), respectively. Group III arthritic rats were treated with curcumin (100 mg/kg, i.p.) on alternate days. Group IV received methotrexate (MTX) (2 mg/kg, i.p.) once in a week. Group-V and VI were treated with MTX (1 mg/kg, i.p.) once in a week and after 30 min received curcumin (30 mg/kg and 100 mg/kg, thrice a week, i.p.) from 10(th) to 45(th) days, respectively. Body weight and the paw volume was measured on 9(th), 16(th), 23(rd), 30(th), 37(th), and 45(th) days. Determination of complete blood cell counts, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration was determined on the 46(th) day. RESULTS: An improvement in body weight and a significant (P < 0.05) reduction in arthritis was observed with the combination treatment as compared to the positive control. A significant improvement in the hematological profile was also observed in rats treated with curcumin and methotrexate. CONCLUSION: The study showed a significant anti-arthritic action and protection from hematological toxicity with the combination treatment of methotrexate and curcumin.
21683061 Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory si Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKBα. Accordingly, DP treatment inhibited TNFα-stimulated increases in NF-κB function and expression of NF-κB target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.
21345249 Molecular targets of natural health products in arthritis. 2011 Feb 3 Patients with rheumatoid arthritis (RA) and osteoarthritis (OA) consume 'natural health products' (NHPs) whose therapeutic efficacy, toxicity and mechanisms of action are poorly understood. In a previous issue of Arthritis Research and Therapy, Haqqi and colleagues characterized IL-1-activated mitogen-activated protein kinase kinase 3 (MKK3) and p38-mitogen-activated protein kinase (MAPK) isoforms in human OA chondrocytes. The cartilageprotective mechanisms of pomegranate extract involve diminishing MKK3-activated p38α, JNK, NF-κB and Runx2 pathways, which regulate inflammatory proteins and cartilage-destroying proteases. Epigallocatechin- 3-gallate, resveratrol, curcumin and other NHP active ingredients suppress multiple inflammatory and catabolic molecular mediators of arthritis. Non-toxicity, reduced severity and incidence of arthritis in animal models warrant testing NHP active ingredients for preventing human OA and RA.
21894293 Contrast-enhanced ultrasonography in inflammatory arthritis. 2011 Sep The degree of inflammation is the keystone of therapy management in rheumatoid arthritis and other arthritides. The assessment of synovial perfusion using power Doppler ultrasound is an important point in the quantification of the joint inflammation but it is limited by the subjectivity of the vascularization grading and incapacity to detect flows in very small vessels. Contrast agent improves the ultrasound ability to depict and quantify blood flows in synovitis. Contrast-enhanced ultrasonography (CEUS) better differentiates synovitis from collection and distinguishes the active synovitis from inactive fibrotic or necrotic pannus. Quantitative assessment of inflammation is possible analyzing the time-intesity curves and by the correct measurement of the synovial thickness. The additional informations and the diagnostic value of CEUS in arthritides are still controversial but its excellent imaging of synovial vessels open the way for further clinical applications. This review aims to discuss the actual knowledges of CEUS in inflammatory arthritis.
22841036 Sleep disordered breathing in patients with primary Sjögren's syndrome: a group controlle 2012 Sep OBJECTIVE: Patients with primary Sjögren's syndrome (pSS) have higher fatigue levels and also suffer from excessive day time sleepiness. The underlying mechanisms for this are not fully understood. Knowing that these patients have higher salivary surface tension, we postulated that sleep disordered breathing (SDB) would be more common and would be a contributor to these symptoms amongst pSS patients. We investigated the prevalence of SDB in pSS patients and its relationship to their symptoms of fatigue and excessive daytime sleepiness. METHODS: This was an observational study of 28 pSS patients (mean±SEM age, 58.7±1.9) and 18 healthy subjects (mean±SEM age, 55.8±3.4) matched for age, sex, and BMI. All the participants underwent an overnight polysomnography. The two groups were compared for fatigue, sleepiness, anxiety, and depression scores, and for the frequency of obstructive apneas and hypopneas during sleep. Correlation analyses were used to explore relationships between sleep study variables and excess sleepiness and fatigue. RESULTS: Fatigue, sleepiness, anxiety and depression symptoms, and sleep onset latency were significantly greater in pSS patients than controls. pSS patients had twice the frequency of obstructive apneas and hypopneas compared with control subjects (median[IQR],18.6/h [10.4-40.1] vs. 9.9/h [6.5-23.4]; p=0.032) and OSA defined as an apnea-hypopnea index >15 events/h of sleep was more prevalent amongst pSS patients than controls (64% vs. 28%; p=0.033). While no significant correlations were found between parameters of sleep disordered breathing and sleepiness scores or fatigue scores in the pSS group, CPAP treatment in a small subset of the pSS who were more severely affected by OSA suggested significant symptomatic benefit. CONCLUSION: OSA appears to be increased in pSS and may be a useful therapeutic target to improve the quality of life of these patients.
22759918 Text-mining applied to autoimmune disease research: the Sjögren's syndrome knowledge base 2012 Jul 3 BACKGROUND: Sjögren's syndrome is a tissue-specific autoimmune disease that affects exocrine tissues, especially salivary glands and lacrimal glands. Despite a large body of evidence gathered over the past 60 years, significant gaps still exist in our understanding of Sjögren's syndrome. The goal of this study was to develop a database that collects and organizes gene and protein expression data from the existing literature for comparative analysis with future gene expression and proteomic studies of Sjögren's syndrome. DESCRIPTION: To catalog the existing knowledge in the field, we used text mining to generate the Sjögren's Syndrome Knowledge Base (SSKB) of published gene/protein data, which were extracted from PubMed using text mining of over 7,700 abstracts and listing approximately 500 potential genes/proteins. The raw data were manually evaluated to remove duplicates and false-positives and assign gene names. The data base was manually curated to 477 entries, including 377 potential functional genes, which were used for enrichment and pathway analysis using gene ontology and KEGG pathway analysis. CONCLUSIONS: The Sjögren's syndrome knowledge base ( http://sskb.umn.edu) can form the foundation for an informed search of existing knowledge in the field as new potential therapeutic targets are identified by conventional or high throughput experimental techniques.
22157220 Gastrointestinal and hepatic manifestations of Sjogren syndrome. 2012 Jan Sjogren syndrome (SS) is an autoimmune disease that affects exocrine glands and therefore may affect the gastrointestinal system, from the mouth, esophagus, and bowel to the liver and pancreas. Oral involvement in SS is mainly characterized by dryness, with a wide spectrum of symptoms, from mild-to-severe xerostomia with dysgeusia and tooth decay. The dysphagia, although common, does not correlate with the reduced salivary flow rate or the dysmotility that may be present. Dyspepsia, found in up to 23% of patients, may be associated with gastritis, reduced acid production, and antiparietal cell antibodies, but rarely pernicious anemia. Pancreatic involvement, although rare, includes pancreatitis and pancreatic insufficiency. The most common causes of liver disease are primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatitis C virus (HCV). Although abnormal liver tests are found in up to 49% of patients, they are usually mild. Although sicca syndrome, abnormal histology of the salivary glands, and abnormal sialograms are common in primary biliary cirrhosis, the antibodies to Ro/SSA or La/SSB antigens are infrequent. Xerostomia, sialadenitis, abnormal salivary flow rates, and abnormal Schirmer test in HCV vary widely among the studies, although the antibodies to Ro/SSA or La/SSB are only 1%. Several studies show that HCV is in saliva, although how this may impact sicca syndrome or SS in HCV is unclear. SS as a disease of exocrine glands affects many parts of the gastrointestinal system.
22124545 The rapid efficacy of abatacept in a patient with rheumatoid vasculitis. 2012 Aug We report a case of rheumatoid vasculitis (RV) that responded well to abatacept, a cytotoxic T lymphocyte-associated antigen 4 (CTLA4)-immunoglobulin fusion protein. A 38-year-old woman developed RV despite treatment with methotrexate and tumor necrosis factor (TNF) inhibitors. The effects of steroid therapy, immunoabsorption plasmapheresis, and interleukin-6 inhibitor were insufficient, however, administration of abatacept rapidly improved her clinical symptoms with almost normalization of the immunological findings. This is the first published case report of the successful treatment of RV with abatacept.
21769488 Adult-onset Still's disease and chronic recurrent multifocal osteomyelitis: a hitherto und 2012 Jun Still's disease and chronic recurrent multifocal osteomyelitis (CRMO) are febrile rheumatic diseases of unknown etiology, which predominantly affect children but can also have their initial manifestation in adults. Both can present as intermittent, relapsing episodes and are considered potential candidates within the expanding spectrum of autoinflammatory disorders, although no genetic abnormalities have been described for either of them. Here, we describe a man with an initial manifestation of abacterial multifocal osteitis at the age of 41. During a relapsing-remitting course of his illness, he increasingly developed symptoms of adult-onset Still's disease (AOSD), and the diagnosis was established according to the Yamaguchi criteria. When treated with anakinra, not only the acute symptoms disappeared promptly, but also the osteitis went into complete remission. This is to our knowledge the first description of a simultaneous occurrence of these two manifestations of autoinflammation in adulthood.
21760509 Activation of the type I interferon pathway in primary Sjögren's syndrome: an update. 2011 Sep PURPOSE OF REVIEW: Recent advances suggest type I interferon (IFN) pathway as an emerging mediator of systemic autoimmunity. This review aims to summarize the latest developments in the biology of type I IFN pathway and its contributory role in the pathogenesis of autoimmune disorders with a particular focus on Sjögren's syndrome. RECENT FINDINGS: Increased circulating type I IFN levels along with upregulated type I IFN inducible genes in salivary gland tissues, peripheral blood and mononuclear cells suggest activation of type I IFN pathway in Sjögren's syndrome. Additional regulatory mechanisms and novel potential suppressors of type I IFN production provide new insights into disease pathogenesis, pointing to type I IFN system as a potential new therapeutic target. SUMMARY: Compelling evidence suggests type I IFN as a key player in pathogenesis of Sjögren's syndrome and an attractive potential therapeutic target. Meticulous stratification of patient subgroups characterized by activation of type I IFN pathway should be performed in carefully designed translational studies.
22733222 [Rare cause of acute liver failure]. 2012 Aug A rare cause of acute liver failure is adult onset Still's disease (AOSD), a systemic inflammatory disorder. We present the case of a 24-year-old woman who presented with acute liver failure necessitating high urgency liver transplantation. The diagnosis of AOSD was established in accordance with the Yamaguchi classification criteria, including arthralgia, fever, sore throat, rash and hepatosplenomegaly. The early detection and therapy of AOSD can possibly avoid the development of liver failure with a poor prognosis.
23192906 Clinical pulmonary involvement in primary Sjogren's syndrome: prevalence, quality of life 2013 Jan OBJECTIVE: The aim of the present study was to describe the prevalence of clinical pulmonary manifestations in primary SS (pSS), and based on registry data, to assess quality of life (QoL) and mortality in these patients. METHODS: Patients with pSS consecutively included in the Norwegian systemic CTD and vasculitis registry (NOSVAR) were investigated for pulmonary manifestations when presenting with clinical pulmonary symptoms. Pulmonary involvement was defined as typical abnormalities identified with high-resolution CT (HRCT) and/or pulmonary function tests (PFTs). RESULTS: Among patients referred from our primary area, Oslo (n = 117), lung involvement was found in 26 patients (22%). In our total cohort (n = 216), 59 patients (27%) were affected. A higher rate of pulmonary complications and trends towards longer disease duration and higher age indicated a selection of more complicated cases referred from outside our primary area. Abnormal HRCTs were found in 50 patients (23%) and PFTs in 34 patients (16%). The Medical Outcomes Study 36-Item Short-Form Health Survey Physical Functioning subscore, was significantly reduced in patients with lung involvement (P = 0.03). Furthermore, a 4-fold increased risk of dying after 10 years of disease among patients with lung involvement (n = 10, 17%) compared with those without lung involvement (n = 7, 4.5%) (P = 0.002) was found. CONCLUSION: We found a high population-based prevalence of clinical pulmonary involvement (22%) among patients with pSS. Moreover, patients with lung involvement had reduced QoL represented by the subscale Physical Functioning, and mortality was increased.
22408869 [Sjögren's syndrome: diagnosis and systemic manifestations]. 2012 Feb Sjögren's syndrome is an autoimmune exocrinopathy characterized by keratoconjunctivis sicca, xerostomia and immune-inflammatory systemic manifestations. The diagnosis is easy to establish when the patient presents with sicca complex as a main symptom, or recurring attacks of parotitis. However, it is way more complex when the disease begins with extraglandular features, such as non erosive polyarticular arthritis, Raynaud's phenomenon, peripheral or central nervous system involvement, kidney disease or interstitial pneumonary disease, or even vasculitis. In such circumstances, diagnosis is often delayed several years.
22210274 A case of uveitis in adult-onset Still's disease with ophthalmologic symptoms. 2013 Jul Adult-onset Still's disease (AOSD) is a rare and systemic inflammatory disorder of unknown etiology and pathogenesis. AOSD is characterized by high fever accompanied by a range of systemic symptoms. However, there are rare cases of AOSD with ophthalmologic symptoms as well as with an obvious causation of corticosteroid withdrawal. In this case, a 43-year-old male patient diagnosed with AOSD showed ocular inflammation after withdrawing from corticosteroid treatment. This patient was treated with prednisolone for AOSD and discharged after achieving complete remission of breathlessness, backache, thoracalgia, joint pain, and spiking fever. The patient unauthorizedly stopped taking prednisolone after he was discharged from the hospital and returned to the Department of Ophthalmology with the complaint of decreased visual acuity in both eyes for half a month and sudden vision loss in the left eye for 3 days. After regular ophthalmologic examinations and fluorescence angiography examination, he was diagnosed with acute panuveitis as the manifestation of AOSD. Uveitis was effectively treated with corticosteroid drugs. This case reported a rare manifestation of AOSD in an ophthalmological system that was associated with the withdrawal of corticosteroid treatment. This report highlighted the therapeutic effect of local and systemic corticosteroid use for AOSD manifested with uveitis. This case is interesting for both rheumatologists and ophthalmologists.
21327424 A case of primary Sjögren's syndrome presenting primarily with central nervous system vas 2012 Mar Sjögren's syndrome is primarily a chronic systemic autoimmune disease that affects exocrine organs. Neurologic symptoms frequently present as peripheral neuropathy due to small vessel vasculitis. Type and prevalence of central nervous system involvement are still controversial. In this report, we present a 35-year-old woman with primary Sjögren's syndrome with central nervous system vasculitic involvement.