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

ID PMID Title PublicationDate abstract
28972439 Suppressor of TCR signaling-2 (STS-2) suppresses arthritis development in mice. 2018 Jul OBJECTIVES: Suppressor of TCR signaling-2 (STS-2) is one of the RA susceptibility genes identified in genome-wide association studies (GWAS). We tried to verify the involvement of STS-2 on the development of autoimmune arthritis in a mouse model. METHODS: STS-2 knock-out (KO) and wild type (WT) mice were immunized with chicken type II collagen (CII). For CD4(+) helper T cell (Th) subset analysis, intracellular cytokines in splenocytes and lymph node cells were stained and analyzed by flow cytometry. Regulatory T cell (Treg) function was analyzed by co-culturing effector CD4(+)T cells and Tregs collected from non-immunized mice. RESULTS: CII-immunized STS-2 KO mice developed arthritis more frequently than WT mice. Although the T cell activation profile and Th subset in spleen and LNs were similar between STS-2 KO and WT mice, STS-2 KO mice showed increased IL-2-producing CD4(+)T cells in spleen when compared with WT mice. Accordingly, STS-2 KO CD4(+)T cells promoted IL-2 production by TCR stimulation. However, STS-2 KO Tregs normally suppressed T cell proliferation. CONCLUSION: We proved that STS-2 is involved in the arthritis development by collagen-induced arthritis. Higher IL-2 production from STS-2 KO T cells is suggested to have a main pathogenic role in arthritis development.
28838228 Red blood cell distribution width is useful in discriminating adult onset Still's disease 2018 Nov BACKGROUND/AIMS: Red blood cell distribution width (RDW) is a value representing the heterogeneity in the size of red blood cell, and it is usually used in distinguishing types of anaemia. Recently, it was reported that it could reflect the burden of inflammation in diverse diseases and their prognosis. Hence, in this study, we investigated whether RDW may contribute to discriminating adult onset Still's disease (AOSD) from sepsis in serious febrile patients within 24 hours after hospitalization. METHODS: We reviewed the medical records and enrolled 21 AOSD patients, 27 sepsis patients and 30 matched healthy controls. We collected at least two laboratory results of variables including RDW within 24 hours after hospitalization, and we calculated their mean values. RESULTS: Sepsis patients showed the significantly increased median white blood cell count, compared to AOSD patients (14,390.0/mm3 vs. 12,390.0/mm3 , p = 0.010). The median RDW in sepsis patients was higher than that in AOSD patients (15.0% vs. 13.3%, p = 0.001), and furthermore, the median RDW in both patient-groups was significantly higher than that in healthy controls. In contrast, the median ferritin level in sepsis patients was lower than that in AOSD patients (544.0 mg/dL vs. 3,756.6 mg/dL, p = 0.001). In multivariate analysis, RDW ≥ 14.8% (odds ratio, 17.549) and ferritin < 2,251.0 mg/dL (odds ratio, 32.414) independently suggested sepsis more than AOSD in patients initially presenting with fever requiring hospitalization. CONCLUSION: RDW might be a rapid and helpful marker for a differential diagnosis between AOSD from sepsis at an early phase.
28577018 A Case of Kidney Involvement in Primary Sjögren's Syndrome. 2017 Jun 3 BACKGROUND Sjögren's syndrome is an autoimmune disorder caused by the infiltration of monocytes in epithelial glandular and extra-glandular tissues. Hallmark presentations include mouth and eye dryness. Although renal involvement is uncommon in primary Sjögren's syndrome (pSS), patients may experience renal tubular acidosis type I (RTA I), tubulointerstitial nephritis, diabetes insipidus (DI), nephrolithiasis, and Fanconi syndrome. However, it is atypical to see more than 1 of these manifestations in a single patient. CASE REPORT We present the case of a 24-year-old woman with polyuria and polydipsia, who was initially diagnosed with nephrogenic diabetes insipidus. She also had chronic hypokalemia and nephrolithiasis. Based on clinical presentation and work up, she was diagnosed with pSS and treated accordingly. CONCLUSIONS This was a pSS patient with tubulointerstitial nephritis, diabetes insipidus, renal tubular acidosis, hypokalemia, and nephrolithiasis, who was receiving symptomatic treatment for diabetes insipidus. Diagnosis and treatment of pSS led to significant improvement in systemic and renal presentations of the patient. pSS should be considered as one of the differential diagnoses in patients with diabetes insipidus and renal tubular acidosis.
28447158 [Ultrasound diagnostics in Sjögren's syndrome]. 2017 Sep Ultrasound of the salivary glands is a specific examination for detecting pathology of salivary glands in the diagnosis of Sjögren's syndrome. It is easy to learn, rapidly performed, non-invasive and inexpensive. Other imaging techniques, such as sialography and scintigraphy, are currently only rarely performed. For the examination, linear ultrasound probes with frequencies between 7 and 12 MHz are recommended. Such probes are already widely available to the rheumatologist performing musculoskeletal ultrasound. The parotid and submandibular glands are bilaterally scanned both in longitudinal and transverse planes as a standard.Normal salivary glands have uniformly hyperechoic and homogeneous tissue. They can be clearly delineated from the surrounding muscles and soft tissue and appear similar to the thyroid gland. The salivary glands are typically hypoechoic and inhomogeneous in Sjögren's syndrome. Focal or diffuse hypoechoic or anechoic foci are found in the glands. The submandibular glands may become atrophic (sagittal diameter <8 mm). Particularly in disease flares, the parotid glands may become enlarged (sagittal diameter >20 mm). The sensitivity for the diagnosis is 60 to 90% and the specificity is over 90%.Doppler sonography does not further improve the diagnostic accuracy. Sonography has thus become an important tool in the diagnosis of Sjögren's syndrome.
28434265 Adipose tissue infiltration in minor salivary glands of patients with Sjögren's syndrome: 2017 Jun Fatty infiltration in minor salivary gland biopsies and its correlation to systemic autoimmune diseases are controversial in the literature. Presence and extent of fatty infiltration in minor salivary glands of 107 Sjögren's syndrome patients and 67 age-matched sicca controls were compared with statistical analyses. No significant difference was found regarding the presence or the extent of fatty infiltration between the two groups. Fatty infiltration seems to be unrelated to Sjögren's syndrome thus its examination in salivary gland biopsy samples cannot improve the diagnostic accuracy of the disease.
27998024 Prevalence of Primary Sjögren's Syndrome in a US Population-Based Cohort. 2017 Oct OBJECTIVE: To report the point prevalence of primary Sjögren's syndrome (SS) in the first US population-based study. METHODS: Cases of all potential primary SS patients living in Olmsted County, Minnesota, on January 1, 2015, were retrieved using Rochester Epidemiology Project resources, and ascertained by manual medical records review. Primary SS cases were defined according to physician diagnosis. The use of diagnostic tests was assessed and the performance of classification criteria was evaluated. The number of prevalent cases in 2015 was also projected based on 1976-2005 incidence data from the same source population. RESULTS: A total of 106 patients with primary SS were included in the study: 86% were female, with a mean ± SD age of 64.6 ± 15.2 years, and a mean ± SD disease duration of 10.5 ± 8.4 years. A majority were anti-SSA positive (75%) and/or anti-SSB positive (58%), but only 22% met American-European Consensus Group or American College of Rheumatology criteria, because the other tests required for disease classification (ocular dryness objective assessment, salivary gland functional or morphologic tests, or salivary gland biopsy) were rarely performed in clinical practice. According to the physician diagnosis, the age- and sex-adjusted prevalence of primary SS was 10.3 per 10,000 inhabitants, but according to classification criteria, this prevalence was only 2.2 per 10,000. The analysis based on previous incidence data projected a similar 2015 prevalence rate of 11.0 per 10,000. CONCLUSION: The prevalence of primary SS in this geographically well-defined population was estimated to be between 2 and 10 per 10,000 inhabitants. Physicians rarely used tests included in the classification criteria to diagnose the disease in this community setting.
28557655 Tear Film Stability in Sjögren Syndrome Patients Treated with Hyaluronic Acid Versus Cros 2017 Sep PURPOSE: To compare the stability of the tear film after instillation of eye drops containing hyaluronic acid (HA) or crosslinked hyaluronic acid (CLHA)-based in patients with Sjögren syndrome-related dry eye (SSDE). METHODS: Forty subjects were included in this study and were divided into 2 groups: the first group (control group) consisted of 20 healthy volunteers; the second group (study group) constituted of 20 suffering from SSDE; before and 5, 30, and 60 min after instillation of eye drops the surface regularity index (SRI) and surface asymmetry index (SAI) were registered. RESULTS: Comparing HA and CLHA, in the control group, SAI show statistically significant difference in the time 0 and in time 5, whereas there is no a statistically significant difference after 30 and 60 min from instillation. For SRI there is no statistically significant difference at any time. In SSDE group there is no statistically significant difference in the time 0 and 5, whereas there is a statistically significant difference after 60 min for SAI, and after 30 and 60 min for SRI from instillation. Both SRI and SAI in dry eyes were significantly greater than in control eyes (P < 0.05). CONCLUSION: Our study showed a better efficacy of CLHA compared with HA in maintaining the stability of the tear film in a patient suffering from SSDE.
28207432 Spontaneous Canalicular Plug Erosion After Punctal Plug Placement. 2017 Apr PURPOSE: To describe a case of keratoconjunctivitis sicca treated with punctal plug placement with the first reported complication of subsequent plug erosion through the canaliculus and extrusion through the lid. METHODS: Punctal plugs were placed in a patient with Sjogren syndrome for treatment of keratoconjunctivitis sicca. More than 12 years later, the plug was noted to have eroded through the canaliculus and extruded through the conjunctiva and lid. RESULTS: The extruded plug was removed, and punctal cautery was performed on 2 other puncta with improved symptom control. CONCLUSIONS: Plug extrusion through the conjunctiva and lid is a possible consequence of punctal plug placement.
28324200 Prevalence and characterization of non-sicca onset primary Sjögren syndrome with intersti 2017 Jun Primary Sjögren syndrome (pSS)-related interstitial lung disease (ILD) involved about 10-20% of patients. In 20% of cases, ILD can be diagnosed before pSS; anyway, few studies have investigated the frequency of ILD as the first clinically relevant manifestation of pSS, generally referred to retrospective studies. Aim of our prospective study was to describe prevalence, clinical, serological, and instrumental features of non-sicca onset pSS patients with interstitial lung involvement. During a period of 48 months, all consecutive patients diagnosed as pSS were enrolled. For all patients, the reason for the first visit was recorded. When present, ILD was categorized as definite, possible, or inconsistent with usual interstitial pneumonia (UIP) pattern, according to the current criteria. ILD was the main presenting symptom in 13/77 new diagnoses of pSS patients; in particular, 6/13 patients were initially diagnosed as idiopathic ILD, and only later developed clinical manifestations suggestive for pSS; ILD-pSS patients were older than others and showed a higher EULAR primary Sjögren's syndrome disease activity index. A radiologic definite or possible UIP pattern was detected in 12/13 pSS. For the first time, we prospectively observed a prevalence of 16.8% of non-sicca onset pSS patients with ILD. Interestingly, UIP pattern was the most frequently detected, while typical autoantibodies were often absent. These features stressed the importance of differential diagnosis in the first stage of the disease, considering the possible poorer prognosis in this subgroup of patients. Multidisciplinary approach is crucial for a correct and early diagnosis, at both onset and follow-up.
29305014 NF-κB and the Transcriptional Control of Inflammation. 2018 The NF-κB transcription factor was discovered 30 years ago and has since emerged as the master regulator of inflammation and immune homeostasis. It achieves this status by means of the large number of important pro- and antiinflammatory factors under its transcriptional control. NF-κB has a central role in inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and autoimmunity, as well as diseases comprising a significant inflammatory component such as cancer and atherosclerosis. Here, we provide an overview of the studies that form the basis of our understanding of the role of NF-κB subunits and their regulators in controlling inflammation. We also describe the emerging importance of posttranslational modifications of NF-κB in the regulation of inflammation, and highlight the future challenges faced by researchers who aim to target NF-κB transcriptional activity for therapeutic benefit in treating chronic inflammatory diseases.
28253537 mRNA profiling identifies low levels of phosphatases dual‐specific phosphatase‐7 (DUSP 2017 Jul Phosphotyrosine phosphatases (PTPs) control phosphorylation levels and, consequently, regulate the output of intracellular signalling networks in health and disease. Despite the high number of PTPs expressed in CD4 T cells and their involvement in autoimmunity, information about the expression profile of PTPs in these cells has not been obtained in patients diagnosed with autoimmune diseases. Here, we compare the expression profile of PTPs in CD4 T cells of healthy volunteers and patients submitted to an early arthritis clinic, due to suspicion of rheumatoid arthritis, an autoimmune disease mediated by CD4 T cells. We found lower transcript levels of the mitogen-activated protein kinase (MAPK) phosphatase dual-specific phosphatase-7 (DUSP7) and the cell division cycle-25B (CDC25B) in T cells of patients. While the low expression level of DUSP7 was restricted to patients with positive rheumatoid factor and anti-citrullinated protein antibodies, the altered expression of CDC25B correlated with the activity of the disease. Low levels of CDC25B might contribute to the progression of the autoimmune arthritis and/or might be consequence of the inflammatory environment in the active disease. The possible role of DUSP7 and CDC25B as biomarkers of the disease in clinical protocols is discussed.
28361180 Evaluation of Endothelial Function by Flow-Mediated Dilation: a Comprehensive Review in Rh 2017 Dec Flow-mediated dilation (FMD) represents a non-invasive marker of endothelial function to evaluate vascular homeostasis, which reflects the effects of several mechanisms, including vessel tone regulation, cell proliferation, and inflammatory responses. Beyond classical atherosclerotic risk factors such as arterial hypertension, diabetes mellitus, smoking, obesity, and dyslipidemia, chronic inflammation contributes to the endothelial dysfunction causing plaque formation and there is growing evidence of a significantly higher cardiovascular morbidity associated with autoimmune diseases. The endothelium reacts to several endogenous and exogenous stimuli, through surface receptors and intracellular signalling, and releases numerous vasoactive substances, including endothelins, prostacyclins, and nitric oxide (NO). Chronic inflammatory rheumatic diseases are commonly associated with decreased endothelial NO production, vascular damage, and premature atherosclerosis. Despite partially eclipsed by pulse wave velocity measure in the modern scientific literature, we provide a comprehensive overview and critically discuss the available data supporting FMD as a surrogate marker of endothelial function and, therefore, its potential role in predicting early atherosclerosis in patients with rheumatic diseases.
28405546 Arthropathy in Dermatology: A Comprehensive Review. 2017 Mar Dermatology and rheumatology are two specialties that deal with significant overlap. In this context, it is important that the dermatologists acquaint themselves with conditions presenting with arthropathy. As the first step, it is essential to know whether the origin of musculoskeletal symptom is articular or extra-articular; inflammatory or noninflammatory; acute or chronic; oligo- or poly-articular. This will help in narrowing down the differential diagnoses as well as in better correlation with the cutaneous symptoms. In this review, we discuss the skin and articular manifestations of common inflammatory and noninflammatory arthropathies including rheumatoid arthritis, spondyloarthropathies, connective tissue disorders, vasculitis, crystal arthropathies, infective arthritis, arthritis associated with degenerative, endocrine and metabolic conditions, etc. We have also added a section on the common cutaneous features associated with the treatment of rheumatologic diseases. A basic understanding of the joint pathologies and associated skin changes will help a long way in the better management of these conditions.
28967798 Tofacitinib in psoriatic arthritis. 2017 Nov Psoriatic arthritis is a heterogeneous disease that has been difficult to manage until the recent advent of biologics. However, there are still unmet medical needs for newer agents. Tofacitinib is a Janus family of kinases inhibitor approved for treating rheumatoid arthritis in many countries and psoriasis in Russia. We reviewed the evidences of tofacitinib in psoriatic arthritis treatment. The efficacy and safety profiles result from Phase III clinical trials (OPAL BROADEN and OPAL BEYOND) and one open-label extension study (OPAL BALANCE). Both tofacitinib 5 or 10 mg twice a day were superior to placebo for American College of Rheumatology 20% improvement criteria response at 3 months and showed significant improvement of skin, enthesitis and dactylitis. Tofacitinib is a promising treatment option for psoriatic arthritis.
29228558 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates arthritic joints through reducin 2017 Nov 14 The pathogenesis of rheumatoid arthritis (RA) has been implicated neutrophil extracellular traps (NETs) formation which could generate autoantigen. Neutrophil contributes to initiate and maintain the inflammatory process in the joint. In this study, we show that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) decreases neutrophil migration by regulating the activity of STAT3, a regulator of IL-6 and MIP-2 expression. PLAG caused a decrease in IL-6 production in the RAW264.7 macrophage cell line and in rheumatoid arthritis-fibroblast-like synoviocytes via the regulation of STAT3 signaling without affecting NF-κB signaling. In a mouse model of collagen-induced arthritis (CIA), arthritic symptoms were recapitulated, with increased IL-6 level in the synovium, and PLAG treatment restored IL-6 to a level comparable to that achieved with commercial therapeutics (such as Remicade or methotrexate). Staining of joint tissue with neutrophil-specific antibody showed that PLAG significantly reduced the infiltration of neutrophils into the joint synovium of CIA mice. The inhibitory effect of PLAG on IL-6/STAT3 or MIP-2 signaling also reduced the migration of differentiated neutrophils in vitro. Therefore, PLAG inhibits the infiltration of destructive neutrophils into inflammatory sites, and can be utilized as a potent therapeutic agent for the treatment of sustained inflammation and joint destruction.
28052563 Self-reported use of natural health products among rheumatology patients: A cross-sectiona 2017 Dec OBJECTIVES: To describe the self-reported use of natural health products (NHPs) and identify characteristics that predict selected NHP use in rheumatology patients. METHODS: We conducted a cross-sectional survey of consecutive rheumatology patients in two major clinics in Edmonton, Alberta. Survey items included demographic data, rheumatologic diagnoses, prescribed medications, NHPs, and information regarding patients' use of NHPs. Selected NHPs of interest - defined to include joint-specific products, oils with putative joint benefits, and other non-vitamin, non-mineral products - were classified by 2 reviewers. The characteristics of selected NHP users and non-users were compared using chi-squared and ANOVA tests, followed by multivariable-adjusted logistic regression. RESULTS: 1063 patients completed the survey (response rate = 36%, mean age 53 [sd 15], 70% female). 36% of respondents reported using one or more of a wide range of selected NHPs (mean 1.8, range 1-9). The most common source of NHP recommendations for selected NHP users were physicians (42%). Significant predictors of selected NHP use were: being female (aOR 1.41, 95%CI [1.05-1.90], p = 0.02), having a post-secondary degree (aOR 1.60 [1.15-2.22], p = 0.005), and the number of non-rheumatic medications (aOR 1.08 [ 1.00-1.15], p = 0.03) and NSAIDs (aOR 1.32 [1.06, 1.63], p = 0.01). Similar findings were observed among only inflammatory arthritis patients. CONCLUSIONS: Our study confirms the frequent use of selected NHPs, possibly to mitigate persistent symptoms of rheumatologic illness. Rheumatologists appear to be trusted sources of advice and recommendations on NHP use and should provide balanced counselling for their patients.
28365217 Tropical arthritogenic alphaviruses. 2018 Mar Tropical alphaviruses have special tropism for bone and joint tissue. Patients can develop chronic rheumatic disorders similar to rheumatoid arthritis and ankylosing spondylitis. The prototype is Chikungunya virus, although other lesser known viruses in our environment such as Sindbis, Ross River, Mayaro, O'nyong nyong and Barmah Forest viruses have the potential to be sped through vectors and cause chronic rheumatic disease. International population movements have increased the numbers of patients diagnosed with these tropical viruses in areas in which they are not endemic. Since they can leave persistent symptoms and affect the quality of life of the patients, it is important that we be aware of them. Changes in ecosystems have favored the expansion of competent mosquitoes, making fears of local transmission in southern Europe a reality. The objective of this review is to provide a clinical approach to the different arthritogenic tropical alphaviruses, especially those in which chronic rheumatic disease is more frequent.
28148584 Psoriatic arthritis: state of the art review. 2017 Feb Psoriatic arthritis (PsA) accounts for around 20% of referrals to the early arthritis clinic and presents a significant diagnostic and management challenge. Early diagnosis is important to prevent long term functional disability and to ensure optimal management of arthritis and key comorbidities. From the rheumatologist's perspective, the differential diagnosis includes rheumatoid arthritis, gout and other inflammatory arthritides. Once diagnosed, it is essential to assess the disease fully, including arthritis, enthesitis, dactylitis, skin/nail disease and axial involvement. Using this information, appropriate treatment can be planned using therapies that are effective at treating the relevant domains of disease. Despite poor data, traditional disease-modifying anti-rheumatic drugs are commonly used and have been effective in observational studies. Following tumour necrosis factor inhibitors, which have proven excellent efficacy in multiple domains of PsA, new biologics are available or in development and will improve treatment options for people with refractory PsA.
28804717 Angiogenesis Dysregulation in Psoriatic Arthritis: Molecular Mechanisms. 2017 There is evidence that psoriatic arthritis is closely linked to angiogenesis. Morphological changes described in blood vessels of psoriatic arthritis joints suggest the presence of a dysregulated angiogenesis resulting in the formation of immature vessels. Even if the reason of this inefficient angiogenesis is still unclear, an imbalance between angiogenic and antiangiogenic factors is probably responsible for inducing a dysregulated angiogenesis in psoriatic arthritis, which seems to be involved in its pathogenesis and clinical features. Nevertheless, among chronic arthritides, while angiogenesis in rheumatoid arthritis has been largely studied with a great amount of literature data, limited data on angiogenesis role in psoriatic arthritis are available. This review article is focused on current knowledge on the mechanisms responsible for dysregulated angiogenesis in psoriatic arthritis.
28836746 Review of Biosimilars of Adalimumab. 2017 May A first fully humanized monoclonal antibody approved by US Food and Drug Administration (FDA) in 2002 was Adalimumab. Clinical efficacy and safety of adalimumab has been assessed in various trials in rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, Crohn's Disease, and ulcerative colitis. It is one of the major sales success among biological and still one of the greatest blockbuster amongst monoclonal antibodies. With the advent of patent expiry of the parent drug HUMIRA, several potential biosimilars have debuted in various markets worldwide. Present article will discuss current situation of molecules that are front-runners to become adalimumab biosimilars with particular stress on Indian market and ZRC3197 (Adalimumab Biosimilar).