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ID PMID Title PublicationDate abstract
31692920 Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rhe 2019 Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by joint involvement, extra-articular manifestations, comorbidities, and increased mortality. In the last few decades, the management of RA has been dramatically improved by the introduction of a treat-to-target approach aiming to prevent joint damage progression. Moreover, the increasing knowledge about disease pathogenesis allowed the development of a new drug class of biologic agents targeted on immune cells and proinflammatory cytokines involved in RA network. Despite the introduction of several targeted drugs, a significant proportion of RA patients still fail to achieve the clinical target; so, more recently the focus of research has been shifted toward the inhibition of kinases involved in the transduction of the inflammatory signal into immune cells. In particular, two Janus kinase (JAK) inhibitors, baricitinib and tofacitinib, have been licensed for the treatment of RA as a consequence of a very favorable profile observed in randomized controlled trials (RCTs) conducted across different RA subpopulations. Both these new compounds are active on the majority of four JAK family members (JAK1, JAK2, JAK3, and TYK2), whereas the most recent emerging approach is directed toward the development of JAK1 selective inhibitors (upadacitinib and filgotinib) with the aim to improve the safety profile by minimizing the effects on JAK3 and, especially, JAK2. In this narrative review, we discuss the rationale for JAK inhibition in RA, with a special focus on the role of JAK1 selective blockade and a detailed description of available data from the results of clinical trials on upadacitinib and filgotinib.
31891115 Factors that influence rheumatologists' anti-tumor necrosis factor alpha prescribing decis 2019 BACKGROUND: Treatment decisions for any disease are usually informed by reference to published clinical guidelines or recommendations. These recommendations can be developed to improve the relative cost-effectiveness of health care and to reduce regional variation in clinical practice. Anti-tumor necrosis factor alpha (anti-TNF) treatments are prescribed for people with rheumatoid arthritis according to specific recommendations by the National Institute for Health and Care Excellence in England. Evidence of regional variation in clinical practice for rheumatoid arthritis may indicate that different factors have an influence on routine prescribing decisions. The aim of this study was to understand the factors that influence rheumatologists' decisions when prescribing anti-TNF treatments for people with rheumatoid arthritis in England. METHODS: Semi-structured one-to-one telephone interviews were performed with senior rheumatologists in different regions across England. The interview schedule addressed recommendations by the National Institute for Health and Care Excellence, prescribing behavior, and perceptions of anti-TNF treatments. Interviews were recorded digitally, transcribed verbatim, and anonymized. Data were analyzed by thematic framework analysis that comprised six stages (familiarization; coding; developing the framework; applying the framework; generating the matrix; interpretation). RESULTS: Eleven rheumatologists (regional distribution - north 36%; midlands: 36%; south: 27%) participated (response rate: 24% of the sampling frame). The mean duration of the interviews was thirty minutes (range: 16 to 56 min). Thirteen factors that influenced anti-TNF prescribing decisions were categorized by three nested primary themes; specific influences were defined as subthemes: (i) External Environment Influences (National Institute for Health and Care Excellence Recommendations; Clinical Commissioning Groups; Cost Pressures; Published Clinical Evidence; Colleagues in Different Hospitals; Pharmaceutical Industry); (ii) Internal Hospital Influences (Systems to Promote Compliance with Clinical Recommendations; Internal Treatment Pathways; Hospital Culture); (iii) Individual-level Influences (Patient Influence; Clinical Autonomy; Consultant Experience; Perception of Disease Activity Score-28 (DAS28) Outcome). CONCLUSIONS: Factors that influenced anti-TNF prescribing decisions were multifaceted, seemed to vary by region, and may facilitate divergence from published clinical recommendations. Strategic behavior appeared to illustrate a conflict between uniform treatment recommendations and clinical autonomy. These influences may contribute to understanding sources of regional variation in clinical practice for rheumatoid arthritis.
31070579 Small vessel multi-organ vasculitis and marantic endocarditis complicating rheumatoid arth 2019 Apr 22 Marantic endocarditis is an extremely rare extra-articular complication of rheumatoid arthritis. To date, documented cases typically occurred in the absence of other systemic features of disease activity. We report a rare and exceptional example of marantic endocarditis secondary to fulminant systemic rheumatoid vasculitis with multi-organ disease. Findings from this case and literature review suggest that marantic endocarditis associated with rheumatoid vasculitis displays a tendency to affect the mitral valve with high risk of embolization.
31731017 Sjögren's syndrome in children with recurrent parotitis. 2020 Feb OBJECTIVE: Optimize the diagnosis of pediatric Sjögren's syndrome in children who present with parotitis. METHODS: Twenty children presented to a pediatric otolaryngology or rheumatology clinic with recurrent parotitis. Presenting symptoms, serologies, sialendoscopy findings, and minor salivary gland biopsy pathology results were reviewed. RESULTS: Twenty patients aged 3-17 years presented with recurrent parotitis. Ten percent of this cohort met the American-European Consensus Group adult diagnostic criteria for Sjögren's syndrome. Forty percent of this cohort met diagnosis of Sjögren's syndrome when utilizing Bartunkova's proposed pediatric criteria for diagnosis of Sjögren's syndrome. CONCLUSION: Sjögren's syndrome is surprisingly common in pediatric patients who present with recurrent parotitis. Otolaryngologists who treat pediatric parotitis should have a high index of suspicion for Sjögren's syndrome. LEVEL OF EVIDENCE: 4.
31376889 Pulmonary Involvement in Sjögren Syndrome. 2019 Sep Sjögren syndrome (SS) is a progressive autoimmune disease characterized by dryness, predominantly of the eyes and mouth, caused by chronic lymphocytic infiltration of the lacrimal and salivary glands. Extraglandular inflammation can lead to systemic manifestations, many of which involve the lungs. Studies in which lung involvement is defined as requiring the presence of respiratory symptoms and either radiograph or pulmonary function test abnormalities quote prevalence estimates of 9% to 22%. The most common lung diseases that occur in relation to SS are airways disease and interstitial lung disease. Evidence-based guidelines to inform treatment recommendations for lung involvement are largely lacking.
31654988 Total Glucosides of Paeony protects against collagen-induced mouse arthritis via inhibitin 2019 Dec BACKGROUND: The development of rheumatoid arthritis (RA) is related to germinal center (GC) response and autoreactive T cells, which mediate adaptive immunity and play an important role in stimulating the production of autoantibodies and pro-inflammatory cytokines by B cells and macrophages. Total Glucosides of Paeony (TGP) has anti-inflammatory, immunomodulatory and analgesic effects and is widely used to treat RA. However, few studies investigated whether the therapeutic effect of TGP is associated with the inhibition of autoimmune response. PURPOSE: The aim of this study was to investigate the effects and mechanisms of TGP on RA. STUDY DESIGN: Type II collagen-induced arthritis (CIA) mouse model was used, and TGP and paeoniflorin were intragastrically treated. METHODS: DBA/1 mice were divided into 5 groups: control, model, positive drug (paeoniflorin) and high- and low-dose TGP group. After 21 days of intragastric administration, the pathological change, inflammation expression and molecular mechanism of each group of mice were detected by Micro-CT, histochemical analysis, ELLSA, Western blot, RT-qPCR and flow cytometry. RESULTS: Our study found that TGP treatment effectively improved inflammation and joint destruction in CIA mice. It reduced the production of serum IgG2a and pro-inflammatory cytokines, including serum interleukin (IL)-21, tumor necrosis factor (TNF)-α and IL-6, and the phosphorylation of NF-κB p65 and STAT3 in a dose-dependent manner. More importantly, TGP could suppress the frequency of germinal center B cells and Tfh cells in the spleen. CONCLUSION: TGP can not only improve symptoms, but also inhibit bone destruction. The therapeutic effect of TGP on CIA is mainly achieved by inhibiting spleen Tfh cell differentiation and GC formation through STAT3 signaling pathway.
31321541 CGRP and Painful Pathologies Other than Headache. 2019 CGRP has long been suspected as a mediator of arthritis pain, although evidence that CGRP directly mediates human musculoskeletal pain remains circumstantial. This chapter describes in depth the evidence surrounding CGRP's association with pain in musculoskeletal disorders and also summarises evidence for CGRP being a direct cause of pain in other conditions. CGRP-immunoreactive nerves are present in musculoskeletal tissues, and CGRP expression is altered in musculoskeletal pain. CGRP modulates musculoskeletal pain through actions both in the periphery and central nervous system. Human observational studies, research on animal arthritis models and the few reported randomised controlled trials in humans of treatments that target CGRP provide the context of CGRP as a possible pain biomarker or mediator in conditions other than migraine.
31618794 Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR cla 2020 Feb OBJECTIVE: Major salivary gland ultrasonography (SGUS) is widely used for the diagnosis of primary Sjögren's syndrome (pSS). Our objective was to assess the contribution of SGUS compared to other items of the 2016 ACR/EULAR pSS classification criteria, based on expert opinion. METHODS: A secure web-based relational database was used by 24 experts from 14 countries to assess 512 realistic vignettes developed from data of patients with suspected pSS. Each vignette provided classification criteria items and information on history, clinical symptoms and SGUS findings. Each expert assessed 64 vignettes, and each vignette was assessed by 3 experts. A diagnosis of pSS was defined according to at least 2 of 3 experts. Validation was performed in the independent French DiapSS cohort of patients with suspected pSS. RESULTS: A criteria-based pSS diagnosis and SGUS findings were independently associated with an expert diagnosis of pSS (P < 0.001). The derived diagnostic weights of individual items in the 2016 ACR/EULAR criteria including SGUS were as follows: anti-SSA, 3; focus score ≥ 1, 3; SGUS score ≥ 2, 1; positive Schirmer's test, 1; dry mouth, 1; and salivary flow rate < 0.1 mL/min, 1. The corrected C statistic area under the curve for the new weighted score was 0.96. Adding SGUS improves the sensitivity from 90.2 % to 95.6% with a quite similar specificity 84.1% versus 82.6%. Results were similar in the DiapSS cohort: adding SGUS improves the sensitivity from 87% to 93%. CONCLUSION: SGUS had similar weight compared to minor items, and its addition improves the performance of the 2016 ACR/EULAR classification criteria.
32151461 Microbiota-mediated mucosal inflammation in arthritis. 2019 Dec Mucosal surfaces are a unique symbiotic environment between a host and a vast and diverse ecology of microbes. These microbes have great immunomodulatory potential with respect to the host organism. Indeed, the mucosal immune system strikes a delicate balance between tolerance of commensal organisms and overt inflammation to ward off pathogens. Disruptions of the microbial ecology at mucosal surfaces has been described in a vast number of different human disease processes including many forms of arthritis, and the resulting implications are still being understood to their fullest. Herein, we review the current state of knowledge in microbe-host interactions as it relates to the development of arthritis through bacterial translocation, bacterial metabolite production, education of the immune response, and molecular mimicry.
31020271 Effects of tofacitinib on the clinical features of periodontitis in patients with rheumato 2019 BACKGROUND: The pathobiology of rheumatoid arthritis (RA) is similar to that of periodontitis in that proinflammatory cytokines play an important pathologic role. There is evidence to suggest that inhibitors of tumor necrosis factor (TNF) and interleukin-6 (IL-6) receptor for the treatment of RA ameliorated periodontal inflammation. However, no study has evaluated the effect of tofacitinib, an oral Janus kinase inhibitor for the treatment of RA, on periodontitis. CASE PRESENTATION: The present report cases are 51- and 43-year-old non-smoking women with RA who demonstrated localized moderate chronic periodontitis. Both cases showed improvement in the periodontal inflammatory condition after 3 months of tofacitinib therapy, although the teeth count and supragingival bacterial plaque level were relatively unchanged. Improvements were also observed in the serum levels of IL-6 in both cases as well as in the serum levels of TNF-α and anti-cyclic citrullinated peptide immunoglobulin G in one case and of rheumatoid factor and matrix metalloproteinase-3 in the other case. Patients who received tofacitinib exhibited an inconsistent clinical response, likely due to the low disease activity of RA at the start of the administration. CONCLUSIONS: These are the first reported cases in which tofacitinib may have a beneficial effect on periodontitis. However, more research is required to understand the relationship between periodontitis and tofacitinib therapy.
30959214 Systemic rheumatic diseases: From biological agents to small molecules. 2019 Jun The development of biologics and small oral molecules has recently changed the scenario of pharmacologic treatment of systemic rheumatic diseases and it has become a real revolution. These drugs have innovative mechanisms of action, based on the inhibition of specific molecular or cellular targets directly involved in disease pathogenesis. This new scenario has lead to a regular update of the management recommendations of several institutions, such as those for Rheumatoid Arthritis treatment that address the use of conventional and biologic therapies including TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, IL-6 inhibitors (tocilizumab and sarilumab), biosimilars and small oral molecules (the JAK inhibitors tofacitinib and baricitinib). Monotherapy, combination therapy, treatment strategies (such as treat-to-target) and the targets of sustained clinical remission or low disease activity are the final goal of the guidelines for rheumatic patients management. In another condition represented by Axial Spondyloarthritis guidelines suggest to start first with non-steroidal anti-inflammatory drugs to improve lifestyle and reduce spine inflammation, but if this is not achieved in 2-4 weeks it is important to consider the use of local therapies (i.e. glucocorticoid injections) or to start biologic therapy such as TNF inhibitors and then eventually switching to another TNF inhibitor or swapping to IL-17 inhibitor. In the case of active Psoriatic Arthritis, guidelines suggest to start with non-steroidal anti-inflammatory drugs and even local glucocorticoid injections especially for oligoarthritis, then to start conventional therapies if lack of efficacy, and finally start biologics or small oral molecules in the presence of drugs toxicity, unfavorable prognostic factors and still active arthritis. In several cases, active Psoriatic Arthritis patients develop a complex clinical condition with comorbidities such as diabetes, inflammatory bowel disease and high risk of infections, and for this reason the American College of Rheumatology and the National Psoriasis Foundation have developed specific guidelines for their management. Biologic and new small molecules therapies are very expensive, but the availability of biosimilars offers the opportunity of reducing the treatment cost and significantly decreasing the cost of originators as well. In fact, we live in a period characterized by the need to rationalize costs of these drugs, to allow treating a higher number of patients and to maintain a homogeneous possibility of treatment choice. For these reasons, we need to follow scientific guidelines and patients' clinical conditions to choose the correct treatment, also based on the economic burden of therapies.
31528840 Experiences of South Asian patients in early inflammatory arthritis clinic: a qualitative 2019 OBJECTIVE: The aim was to explore how UK South Asian patients living with RA interact with health care professionals and experience receiving health information in an early inflammatory arthritis clinic. METHODS: A semi-structured interview schedule, designed in conjunction with a patient partner, was used for face-to-face interviews. South Asian participants with RA were recruited from Central Manchester University Hospitals National Health Service Foundation Trust. Data were recorded and transcribed by an independent company. Data were analysed using inductive thematic analysis. RESULTS: Fifteen participants were interviewed. Three predominant themes emerged around participants' experiences and interaction with health care professionals in early inflammatory arthritis clinic. First, 'the personal experiences of RA and cultural link to early inflammatory arthritis clinic', where participants described the impact of RA as individuals and their altered roles within their cultural setting. Second, 'experiences of interacting and receiving information in the early inflammatory arthritis clinic', where participants described their limited engagement with health care professionals and the quality of information discussed in the clinic. Third, 'views on future content for early inflammatory arthritis clinics', where participants highlighted new innovative ideas to build on current practice. CONCLUSION: We believe this to be the first study to generate insight into the experiences of South Asian patients of interacting with health care professionals while attending an early inflammatory arthritis clinic. Policy directives aimed at improving access to services and delivery of information for ethnic minority groups in early inflammatory arthritis clinics should include consideration of the different roles of cultures. Professionals should be cognizant of the factors that drive health inequalities and focus on improving service delivery.
31700250 Safety of Intra-articular Methotrexate Injection With and Without Electroporation for Infl 2019 The general disease activity of patients with rheumatoid arthritis (RA) is well controlled by disease-modifying antirheumatic drugs, but local inflammation often remains in a few small joints. Electroporation, making small pores in cell membranes, has proven useful for drug delivery. The safety of a combination therapy of methotrexate (MTX) and electroporation for local joint inflammation in RA was investigated in a prospective, randomized, double-blind, placebo-controlled, exploratory study (UMIN000016606). The patients were randomly allocated to groups receiving a combination of MTX and electroporation (True-EP) and MTX alone (False-EP) groups. The MTX solution was injected into finger joints under ultrasound guidance. The True-EP group underwent electroporation with MTX, and the False-EP group was given MTX but only pinched using the electrode. The ultrasound grade, disease activity, and safety were evaluated from baseline to 26 weeks. Five patients (3 True-EP and 2 False-EP) with a mean age of 57.4 years and disease duration of 10.2 years were enrolled. The grey-scale grade was unchanged in 3 cases (2 True-EP and 1 False-EP) and increased in 2 cases (1 True-EP and 1 False-EP). Disease activity was alleviated in 3 cases (2 True-EP and 1 False-EP). No patients experienced burned skin or electroshock. The combination therapy of electroporation and MTX was safe for RA patients.
31302619 Fever with persistent flagellate erythema in a primigravida: a rare presentation of adult- 2019 Jul 12 We describe a case of a 25-year-old primigravida, who presented to the emergency department with fever, arthralgia and erythematous maculopapular eruption. There was confluent violaceous macular erythema on the arms, v-area of the neck and upper back with periorbital oedema, mimicking dermatomyositis. There was flagellate erythema on the back. Skin biopsy and systemic investigations helped to rule out dermatomyositis. A final diagnosis of adult-onset Still's disease with atypical cutaneous manifestations was made. This atypical variant is associated with a worse prognosis. Early recognition of this clinical variant can be life-saving for the patient.
31012366 P300 values in patients diagnosed with primary Sjogren syndrome. 2019 Mar PURPOSE: Primary Sjogren syndrome (PSS) is an autoimmune disease characterized by symptoms of a dry mouth and eyes, in which other organs and systems are widely involved. Central nervous system (CNS) involvement in PSS is reported in a wide range between 2.5-60%. The reason is that the clinical picture can remain asymptomatic despite the presence of CNS involvement in the disease process. In this study, our aim was to evaluate subclinical cognitive impairment in patients with PSS by investigating P300 potential parameters. METHOD: Forty-three female patients with PSS (mean age: 52.6 ± 11.4 years) and 35 healthy female controls (mean age: 54.5 ± 8.09 years) were included in the study. Mini-Mental State evaluations (MMSE) and brain MRI were performed in the patient and control groups. An event-related evoked potentials test (P300) was applied to those with normal MMSE. RESULTS: The P300 latencies of patients with PSS were significantly longer compared with the control group (p = .019). In patients with PSS, there was no difference in P300 parameters between ANA, Anti-SSA, Anti-SSB-positive and negative patients, and patients with or without sedimentation and CRP elevation. In addition, brain MRI revealed no statistically significant difference between patients with PSS with and without ischemic gliotic lesions (p=.48). CONCLUSION: In our study, P300 latency was also found to be significantly longer in patients who had no white matter change. We believe that prolonged P300 potential latencies without associated white matter lesions in brain imaging may be associated with subclinical CNS involvement.
31591677 Osteoclastic microRNAs and their translational potential in skeletal diseases. 2019 Sep Skeleton undergoes constant remodeling process to maintain healthy bone mass. However, in pathological conditions, bone remodeling is deregulated, resulting in unbalanced bone resorption and formation. Abnormal osteoclast formation and activation play a key role in osteolysis, such as in rheumatoid arthritis and osteoporosis. As potential therapeutic targets or biomarkers, miRNAs have gained rapidly growing research and clinical attention. miRNA-based therapeutics is recently entering a new era for disease treatment. Such progress is emerging in treatment of skeletal diseases. In this review, we discuss miRNA biogenesis, advances in the strategies for miRNA target identification, important miRNAs involved in osteoclastogenesis and disease models, their regulated mechanisms, and translational potential and challenges in bone homeostasis and related diseases.
29529894 Evaluation of systemic activity of pediatric primary Sjögren's syndrome by EULAR Sjögren 2019 Jan OBJECTIVES: The purpose of this study is to evaluate systemic disease activity of pediatric Sjögren's syndrome (SS) using European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). METHODS: We retrospectively reviewed medical records of patients with SS who have been diagnosed according to 1999 Japanese diagnostic criteria for SS before 16 years old at KKR Sapporo Medical Center, Hokkaido University Hospital, and affiliated hospitals. We analyzed clinical and laboratory data and calculated ESSDAI at both diagnosis and peak activity. RESULTS: Twenty-five patients (2 boys and 23 girls) were enrolled. Only 4 patients had sicca symptoms at diagnosis. Mean ESSDAI scores at diagnosis and peak activity were 12.68 (2-31) and 15.08 (2-38), respectively. Only 3 patients were inactive (ESSDAI score <5) at diagnosis. Frequently involved domains at diagnosis were the biological (96%) followed by the constitutional (68%), glandular (44%), articular (44%), cutaneous domains (28%), renal (16%), and central nervous system (12%). At peak activity, biological domain (96%) was followed by the constitutional (72%), glandular (60%), articular (44%), cutaneous (28%), central nervous system (20%), and renal domains (16%). CONCLUSION: Pediatric SS is suspected from active systemic manifestations. The items of ESSDAI are useful clues to the diagnosis of pediatric SS.
31909075 Nonsurgical management of temporomandibular joint autoimmune disorders. 2019 INTRODUCTION: Temporomandibular disorders (TMD) are observed in a number of autoimmune diseases but limited studies have assessed the effect of autoimmune diseases on TMD. Therefore, the present review article was conducted to determine the effect of autoimmune diseases on TMD. METHODS: International databases, including Web of Sciences, PubMed and Scopus, were searched in order to find related articles. The search key words were; temporomandibular joint (TMJ) autoimmune disorders, TMJ, TMD, medical therapy and non-invasive, local and systemic management. Published articles from June, 2010 to June, 2019 were included in the review. RESULTS: A total of 11 related articles including rheumatoid arthritis (RA), lupus erythematosus and systemic sclerosis were found. All articles noted that TMJ has unique features that distinguishes it from other human body joints. Cases of TMJ injury and TMD require specific treatments. Therefore, early diagnosis of TMD is essential. It was also mentioned in the articles that the collagen-induced arthritis (CIA) method is a suitable method for investigating TMD and its relationship with RA. Treatment methods included oral steroids, Disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, methotrexate 75 mg, and combination therapy with methotrexate. CONCLUSION: Based on the results of this study, TMD exists in some autoimmune diseases, including RA, lupus erythematosus and systemic sclerosis. Therefore, there should be an interdisciplinary collaboration between physicians and dentists in order to choose the best conservative treatment and medication therapy for TMD to reduce the progression and pain associated with this type of disorder.
31055973 The role of damage-associated molecular pattern for pathogenesis and biomarkers in adult-o 2019 Jun Introduction: Adult-onset Still's disease (AOSD) is a systemic inflammatory disease, which presents itself as an adult form of systemic juvenile idiopathic arthritis. Innate immune activation driven by a combination of genetic and environmental factors is the primary mechanism underlying disease pathogenesis in AOSD patients. Few biomarkers have been identified for AOSD diagnosis or for the assessment of disease activity or prediction of clinical outcomes. Damage-associated molecular patterns (DAMPs) can activate innate immunity, resulting in tissue damage. Changes in several DAMPs are associated with disease pathogenesis in AOSD patients. Areas covered: This review describes the role of DAMPs in AOSD pathogenesis and discusses their potential for use as disease biomarkers. Together with overall pathogenesis of AOSD, high-mobility group box-1, advanced glycation end products, S100 proteins, and neutrophil extracellular traps are introduced and discussed in detail. Expert opinion: The activation of macrophages and neutrophils is associated with several DAMPs, causing high concentrations of proinflammatory cytokines in AOSD patients. Involvement of certain DAMPs in AOSD patients is well documented due to the presence of sterile inflammation; however, direct evidence for some DAMPs is lacking. Further research into the role of DAMP molecules in AOSD patients may reveal new biomarkers and provide targets for disease intervention.
31105830 MicroRNA-147 negatively regulates expression of toll-like receptor-7 in rat macrophages an 2019 Background/Introduction: Aberrant expression of Toll like receptors (TLR) plays a vital role in pathogenesis of rheumatoid arthritis (RA). Micro RNAs (miRs) could play important role in the related signaling pathways. The present study was undertaken to establish the link between miR-147 and TLR-7 in rat macrophages (in vitro) and in pristane (PS) induced arthritic rats. METHODOLOGY: Dual luciferase assay was done to confirm the interaction between miR-147 and TLR-7. The effect of miR-147 on regulation of TLR-7 was done by RT-qPCR and Immunoblotting studies in rat macrophages (ATCC(®) CRL-2192(TM)) after treating them with miR-147 mimics and inhibitors. R-848 (Imiquimod) was used as TLR-7 stimulant, the mRNA and protein expression levels of IFN-β and TNF-α were recorded to determine the regulation of TLR-7. The levels of miR-147 and TLR-7 were evaluated during induction of rat bone marrow derived macrophage in the PS induced rat macrophages and spleens of methotrexate exposed rats. The miR-147 mimics was injected intraperitoneal to the PS treated rats and the severity of arthritis was studied. RESULTS: The study confirmed TLR-7 mRNA as the potential target of miR-147 in rats. Alterations in miR-147 by transfecting mimics or inhibitors in ATCC(®) CRL-2192(TM) cells exhibited suppression and amelioration of TLR-7 and cytokine expression. The alteration in expression of miR-147 was inversely correlated with expression of TLR-7 during bone marrow derived macrophages induction in PS exposed cells and spleens. The abnormal expression was reversed in spleens of methotrexate treated arthritic rats. The treatment of miR-147 mimic caused suppression in expression of TLR-7 and improved the severity of arthritis in PS induced arthritic rats. CONCLUSIONS: MiR-147 inversely regulates the TLR-7 signaling by targeting TLR-7 itself both in vivo and in vitro. The study provides a novel approach for conditions involving abnormal TLR-7 expression in arthritis.