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ID PMID Title PublicationDate abstract
29480357 Maintenance of Remission with Etanercept-DMARD Combination Therapy Compared with DMARDs Al 2018 Jun INTRODUCTION: To compare etanercept (ETN) and placebo (PBO) for maintaining low disease activity (LDA) achieved with ETN in patients with rheumatoid arthritis (RA) from Africa and the Middle East. METHODS: In this subset analysis of the Treat-to-Target trial (ClinicalTrials.gov identifier NCT01981473), 53 adult patients with moderate-to-severe RA nonresponsive to methotrexate were treated with 50 mg ETN/week for 24 weeks (Period 1). Patients achieving LDA were randomized to continue ETN treatment or switched to PBO for an additional 28 weeks (Period 2). The proportion of patients maintaining LDA or remission in each arm at the end of Period 2 was determined. Additional efficacy and patient-reported outcomes (PROs) were also evaluated. RESULTS: During Period 1, 51 patients achieved LDA according to the disease activity score-28 joints-erythrocyte sedimentation rate (DAS28-ESR LDA) and 30 achieved remission. At week 52, nine of 22 and eight of 29 in the ETN and PBO groups, respectively, remained in DAS28-ESR LDA without experiencing a flare. Additionally, six of 14 and five of 16 in the ETN and PBO groups, respectively, remained in remission. Among patients experiencing a flare during Period 2, 13 of 22 and 21 of 29 received ETN or PBO, respectively. The median time to flare was 193 and 87 days in the ETN and PBO groups, respectively. At week 52, consistently more patients in the ETN group than in the PBO group achieved predetermined efficacy and PRO endpoints. CONCLUSIONS: These data suggest continuing ETN maintenance therapy is beneficial to patients after they have achieved their treatment target. However, this subset analysis is limited by the small patient population and must be interpreted with caution. FUNDING: Pfizer. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT0198147.
30524940 Potential role of platelets for atherosclerotic events in rheumatoid arthritis. 2018 Dec Rheumatoid arthritis (RA) is a chronic inflammatory disease with increased risk of cardiovascular events and mortality that can be attributed to accelerated atherosclerosis. This pilot study aimed to investigate if changes in blood parameters were compatible with atherosclerotic events in RA patients. To this aim, 45 RA women (aged more than 18 years), and 25 age and gender-matched healthy donors (HD) were included. Biomarkers of oxidative stress, platelet activation and platelet aggregation were analysed in RA patients at baseline and after six months of treatment with disease modifying anti-rheumatic drugs (DMARDs). Flow cytometry analysis revealed that ca. 4% of platelets was in activated state (evaluated in term of Annexin V and PAC-1 positivity) in RA patients at baseline, and that the 76% of platelets displayed mitochondrial hyperpolarization. Moreover, platelets from RA patients at baseline aggregated more than those from HD after whole blood treatment with adenosine diphosphate. Interestingly, platelet aggregation in patients at baseline positively correlated with disease activity measured by DAS28 score. After six months of treatment with DMARDs, platelet activation and platelet aggregation reached values comparable to those of HD. Our preliminary data suggest that platelets might play an active role in the atherosclerosis occurring in RA patients.
30498726 Low prevalence of rheumatoid arthritis among patients with pre-existing type 2 diabetes me 2018 Oct BACKGROUND: Type 2 diabetes mellitus (T2DM) is a non-autoimmune disease characterized by chronic hyperglycemia and increased non-enzymatic glycation of amino groups. Glycation occurs through a series of events eventually leading to the formation of irreversible "advanced glycation end-products" (AGEs). AGEs may affect the function of long-lived proteins, including cytokines, immunoglobulins and their receptors, resulting in a "less active" immune system. We aimed to test the hypothesis that a common inflammatory chronic disease, such as rheumatoid arthritis (RA), in which the earliest event is an inflammatory response to unknown stimulus, has a lower prevalence in these patients than in normoglycemic, non-diabetic subjects. METHODS: In this study, we compared the prevalence of RA in a prospectively followed outpatient cohort of patients with T2DM patients (n=1,630) with a control, matched, non-diabetic population (n=1,630). RESULTS: Among non-diabetic controls, 13 patients (prevalence 0.80%) with RA were identified. An almost 3-fold lower prevalence of RA (0.25%) was found in consecutive patients with T2DM (P=0.029). Most of the RA cases among participants with T2DM were diagnosed early after diabetes onset. The onset of RA in patients with T2DM occurred at significantly older age (64±15 years) as compared to the non-diabetes group (48±18 years; P=0.004). CONCLUSIONS: The prevalence of RA is lower and occurs in an older age in patients with pre-existing T2DM in comparison with people without T2DM.
30122937 Azilsartan improves the effects of etanercept in patients with active rheumatoid arthritis 2018 BACKGROUND AND AIM: Much evidence has emerged documenting the involvement of the renin-angiotensin system (RAS) in inflammatory processes. The objective of this study was to evaluate the effects of blocking RAS with azilsartan (Azil) on the clinical efficacy of etanercept (Etan) in patients with active rheumatoid arthritis (RA). PATIENTS AND METHODS: Forty-two patients diagnosed with active RA and poorly responding to methotrexate were enrolled in this pilot clinical study. They were randomly allocated into two groups, and treated with either Etan (50 mg/week) and placebo or the same dose of Etan with Azil (20 mg/day) for 90 days. The clinical outcome was evaluated using the Disease Activity Score-28 joint (DAS-28), simplified disease activity index (SDAI), clinical disease activity index (CDAI) and the health assessment questionnaire disease index (HAQ-DI). Blood samples were obtained for the assessment of C-reactive protein and erythrocyte sedimentation rate at baseline and after 90 days. RESULTS: The markers of pain and disease activity, C-reactive protein and erythrocyte sedimentation rate were significantly improved when Azil was used, as an adjuvant with Etan, compared with the use of Etan and placebo. CONCLUSION: Blocking RAS with azilsartan may improve the effects of etanercept on the clinical markers of pain and disease severity of patients with active RA not responding to methotrexate.
29422864 Clinical Pharmacogenetic Models of Treatment Response to Methotrexate Monotherapy in Slove 2018 Objectives: Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but nevertheless 30% of patients experience MTX inefficacy. Our aim was to develop a clinical pharmacogenetic model to predict which RA patients will not respond to MTX monotherapy. We also assessed whether this model can be generalized to other populations by validating it on a group of Serbian RA patients. Methods: In 110 RA Slovenian patients, data on clinical factors and 34 polymorphisms in MTX pathway were analyzed by Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression to select variables associated with the disease activity as measured by Disease Activity Score (DAS28) score after 6 months of MTX monotherapy. A clinical pharmacogenetic index was constructed from penalized regression coefficients with absolute value above 0.05. This index was cross-validated and also independently validated on 133 Serbian RA patients. Results: A clinical pharmacogenetic index for prediction of DAS28 after 6 months of MTX monotherapy in Slovenian RA patients consisted of DAS28 score at diagnosis, presence of erosions, MTX dose, Solute Carrier Family 19 Member 1 (SLC19A1) rs1051266, Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) rs2306283, Thymidylate Synthase (TYMS), and Adenosine Monophosphate Deaminase 1 (AMPD1) rs17602729. It correctly classified 69% of Slovenian patients as responders or nonresponders and explained 30% of variability in DAS28 after 6 months of MTX monotherapy. Testing for validity in another population showed that it classified correctly only 22.5% of Serbian RA patients. Conclusions: We developed a clinical pharmacogenetic model for DAS28 after 6 months of MTX monotherapy in Slovenian RA patients by combining clinical and genetic variables. The clinical pharmacogenetic index developed for Slovenian patients did not perform well on Serbian patients, presumably due to the differences in patients' characteristics and clinical management between the two groups.
29955385 Clinical and radiographic course of early undifferentiated arthritis under treatment is no 2018 OBJECTIVE: To analyse whether early arthritis patients who do not fulfil the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 classification criteria for rheumatoid arthritis (RA) have a different course of the disease dependent on whether they can or cannot be classified as RA because of radiographic disease (EULAR task force) at diagnosis. METHODS: For this observational study within the Swiss RA cohort SCQM, we included patients with early undifferentiated arthritis (disease duration ≤1 year), who had not received any previous disease-modifying antirheumatic drugs (DMARDs). 2010 ACR/EULAR criteria negative patients were separated into two groups (radiographic vs non-radiographic arthritis) depending on whether or not they had radiographic changes defined as erosive disease by a EULAR task force (≥3 joints with erosions). The primary outcome measure was the radiographic progression detected employing the Ratingen erosion score. Health Assessment Questionnaire (HAQ) and DAS-28 were used as secondary outcome measures. The average observation period was 4 years. RESULTS: A total of 592 patients were analysed. 240 were not classifiable as RA by application of the 2010 ACR/EULAR criteria at baseline. In 57 patients, radiographs at the first visit were not available. 133 patients had radiographic arthritis and 50 non-radiographic arthritis. Treatment was initiated in all patients with DMARDs, mostly methotrexate. No differences in DAS-28 and HAQ scores were found during follow-up. The average erosion scores were higher among patients with initially radiographic arthritis throughout the study. The progression of erosion scores over time, however, was higher in patients with initially non-radiographic arthritis with less subsequent radiological progression (3.3 erosions/year vs 0.4, respectively, p<0.0001). CONCLUSIONS: The clinical and radiographic course of early undifferentiated arthritis under treatment was not dependent on the presence of erosions in three or more joints (ie, the definition of radiographic disease by the EULAR task force) at diagnosis in our cohort.
30007486 Guideline recommended treatment to targets of cardiovascular risk is inadequate in patient 2019 Jan 1 OBJECTIVES: Patients with inflammatory joint diseases (IJD) have an increased risk of cardiovascular disease (CVD). Our goal was to examine indications for, and use of, lipid-lowering therapy (LLT) and antihypertensive treatment (AntiHT) in patients with IJD. Furthermore, to investigate the frequency of low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) goal attainment among IJD patients. METHODS: The cohort was derived from the NOrwegian Collaboration on Atherosclerosis in patients with Rheumatic joint diseases (NOCAR). Indications for AntiHT were: systolic/diastolic BP ≥ 140/90 mm Hg, self-reported hypertension or AntiHT. CVD risk was estimated by the systematic coronary risk evaluation (SCORE) algorithm. LDL-c goals were <2.6 mmol/L in case of diabetes, total cholesterol > 8 mmol/L or a SCORE estimate ≥ 5%, and <1.8 mmol/L for those with established CVD or SCORE ≥ 10%. Comparisons across IJD entities were performed using age and sex adjusted logistic regression. RESULTS: In total, 2277 patients (rheumatoid arthritis: 1376, axial spondyloarthritis: 474, psoriatic arthritis: 427) were included. LLT and AntiHT were indicated in 36.1% and 52.6% of the patients, of whom 37.6% and 47.0% were untreated, respectively. LDL-c and BP targets were obtained in 26.2% and 26.3%, respectively. Guideline recommended treatment and/or corresponding treatment targets were not initiated or obtained in approximately 50%. Rheumatoid arthritis patients were particularly likely to be undertreated with LLT, whereas hypertension undertreatment was most common in psoriatic arthritis. CONCLUSIONS: Inadequate CVD prevention encompasses all the three major IJD entities. The unmet need for CVD preventive measures is not only prevalent in RA, but exists across all the major IJD entities.
30213687 Poly-γ-glutamic acid suppresses osteoclastogenesis in human osteoclast precursors and pre 2018 Nov Poly-γ-glutamic acid (γ-PGA), a natural polymer derived from Bacillus subtilis, shows anti-inflammatory activity. However, the effects of γ-PGA on osteoclasts, which are important cells for joint destruction in inflammatory diseases such as rheumatoid arthritis (RA), have not yet been reported. In this study, we show that γ-PGA markedly inhibits osteoclast differentiation in normal PBMC-derived osteoclast precursors and in synovial fluid macrophages of patients with RA. γ-PGA also reduces RANK expression by down-regulating M-CSF receptors. Additionally, oral administration of γ-PGA attenuated bone destruction in a collagen-induced arthritis (CIA) model, demonstrating decreases in inflammation, cartilage damage, and osteoclast formation in histological analyses. Taken together, these data suggest that γ-PGA could be a good candidate for therapeutic prevention of joint destruction in RA.
30206553 The use of biologic therapies in uveitis. 2018 Apr PURPOSE: Non-infectious uveitis has been long controlled with the use of corticosteroids with many side effects and poor control in some cases. The purpose of this paper was to assess the different biologic agents (in this case infliximab and adalimumab) and to compare their efficacy in the treatment of uveitis. RESULTS: Adalimumab has been proven very successful in replacing or aiding corticosteroid therapy in different autoimmune mediated uveitis (Juvenile Idiopathic Arthritis, Rheumatoid arthritis, sarcoidosis) whereas infliximab has been used intravenously and recently intravitreally with very promising results in controlling Behcet's related uveitis. CONCLUSION: Biologic Response Modifiers represent the future of therapy in immune-mediated uveitis. Abbreviations AU = Anterior Uveitis, BCVA = Best Corrected Visual Acuity, BRM = Biologic Response Modifiers, CME = Cystoid Macular Oedema, CPR = C Protein Reactive, ESR = Erythrocyte Sediment Rate, HSV = Herpes Simplex Virus, ICAM = Intercellular Adhesion Molecules, IMT = Immunomodulatory Therapy, JIA = Juvenile Idiopathic Arthritis, MMP = Matrix Metalloproteinases, MTX = Methotrexate, RA = Rheumatoid Arthritis, TB = Tuberculosis, VCAM = Vascular Adhesion Molecules.
31308804 Panax ginseng: a candidate herbal medicine for autoimmune disease. 2019 Jul Panax ginseng Meyer (P. ginseng; Korean ginseng) is well known for its medicinal properties. It can alleviate pathological symptoms, promote health, and prevent potential diseases via its anti-inflammatory, antioxidant, homeostatic, and other positive effects on biological metabolism. Although many studies have determined effects of P. ginseng on various diseases, such as cardiovascular, neurological, and immunological diseases, little is known about the effect of P. ginseng on autoimmune diseases. Here, we review a few reports about effects of P. ginseng on autoimmune diseases (e.g., multiple sclerosis, Crohn's disease, ulcerative colitis, atopic dermatitis, and rheumatoid arthritis) and suggest the possibility of P. ginseng as a candidate herbal medicine to prevent and treat autoimmune diseases as well as the need to study it.
29869008 Novel insights into the role of inflammasomes in autoimmune and metabolic rheumatic diseas 2018 Aug Inflammasomes are large intracellular complexes that induce inflammation in response to exogenous and endogenous damage signals. They regulate production and release of the proinflammatory cytokines IL-1β and IL-18, playing a defensive role against infections. Inflammasomes have also been involved in the pathogenesis of a wide range of autoinflammatory conditions that are caused by dysregulation of the IL-1 pathway, such as cryopyrinopathies and hereditary periodic fever syndromes. On top of that, research in recent years suggests that defects in inflammasome regulation and signaling associate with a number of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and others. In this review, we describe the inflammasome and mechanisms that trigger it, provide a brief review of autoinflammatory disorders and discuss the current understanding and emerging data from experimental and clinical studies for the role of the innate immune system and inflammasomes in the biology and pathogenesis of systemic autoimmune diseases.
28752573 Adiponectin exerts a potent anti-arthritic effect and insulin resistance in collagen-induc 2018 Aug AIM: Previous research has shown that adiponectin (AD) induces severe insulin resistance (IR) and exhibits pro-inflammatory effect, so it could serve as a useful risk biomarker in rheumatoid arthritis (RA). The present study aims to evaluate the effect of AD on IR and anti-arthritis in collagen-induced arthritic (CIA) rats. METHOD: After immunization with bovine type II collagen (CII), Wistar rats were administered with AD (60 μg/kg/day) or saline into the ankle joint cavity of the left hind leg for 15 days. The severity of arthritis was clinically and histologically assessed. Arthritis score was recorded every other day for each paw. Paw volume was measured on alternate days to monitor the progression of the disease in the arthritic control group. Tumor necrosis factor (TNF)-α, interleukin (IL)-1, AD, insulin and fasting glucose were measured in sera. Histopathology of joint synovial tissues was also examined. RESULTS: Treatment with AD resulted in significantly delayed onset of arthritis as well as decreased clinical arthritis and histopathological severity scores. AD reduced both serum fasting glucose, TNF-α, IL-1 and IR. Histological analysis confirmed treatment with AD suppressed joint synovial inflammation and immunohistochemical expression of TNF-α compared to the CIA group. Surprisingly, adiponectin levels measured by enzyme-linked immunosorbent assay in serum were significantly increased in CIA rats compared to the normal group. CONCLUSIONS: Adiponectin might display anti-inflammatory effects. These results suggest that AD may be a potential immunosuppressant for the treatment of RA linked to metabolic disease.
29862859 ABBV-105, a selective and irreversible inhibitor of Bruton's tyrosine kinase, is efficacio 2019 May OBJECTIVES: Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase required for intracellular signaling downstream of multiple immunoreceptors. We evaluated ABBV-105, a covalent BTK inhibitor, using in vitro and in vivo assays to determine potency, selectivity, and efficacy to validate the therapeutic potential of ABBV-105 in inflammatory disease. METHODS: ABBV-105 potency and selectivity were evaluated in enzymatic and cellular assays. The impact of ABBV-105 on B cell function in vivo was assessed using mechanistic models of antibody production. Efficacy of ABBV-105 in chronic inflammatory disease was evaluated in animal models of arthritis and lupus. Measurement of BTK occupancy was employed as a target engagement biomarker. RESULTS: ABBV-105 irreversibly inhibits BTK, demonstrating superior kinome selectivity and is potent in B cell receptor, Fc receptor, and TLR-9-dependent cellular assays. Oral administration resulted in rapid clearance in plasma, but maintenance of BTK splenic occupancy. ABBV-105 inhibited antibody responses to thymus-independent and thymus-dependent antigens, paw swelling and bone destruction in rat collagen induced arthritis, and reduced disease in an IFNα-accelerated lupus nephritis model. BTK occupancy in disease models correlated with in vivo efficacy. CONCLUSION: ABBV-105, a selective BTK inhibitor, demonstrates compelling efficacy in pre-clinical mechanistic models of antibody production and in models of rheumatoid arthritis and lupus.
30723786 Alpha-1 Antitrypsin Therapy for Autoimmune Disorders. 2018 Oct 5 Autoimmune diseases are conditions caused by an over reactive immune system that attacks self-tissues and organs. Although the pathogenesis of autoimmune disease is complex and multi-factorial, inflammation is commonly involved. Therefore, anti-inflammatory therapies hold potential for the treatment of autoimmune diseases. However, long-term control of inflammation is challenging and most of the currently used drugs have side effects. Alpha-1 antitrypsin (AAT) is an anti-inflammatory protein with a well-known safety profile. The therapeutic potential of AAT has been tested in several autoimmune disease models. The first study using a recombinant adeno-associated viral (rAAV) vector showed that AAT gene transfer prevented the development of type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse model. Subsequent studies showed that treatment with AAT protein prevented and reversed type 1 diabetes. The beneficial effects of AAT treatment have also been observed in other autoimmune disease models such as rheumatoid arthritis and systemic lupus erythematosus. This paper reviews the therapeutic application of AAT and discusses possible mechanisms of action in various autoimmune diseases.
29516402 Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases. 2018 Jun Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications.
29409370 Clinical practice guideline for Sjögren's syndrome 2017. 2018 May OBJECTIVES: The objective of this study is to develop clinical practice guideline (CPG) for Sjögren's syndrome (SS) based on recently available clinical and therapeutic evidences. METHODS: The CPG committee for SS was organized by the Research Team for Autoimmune Diseases, Research Program for Intractable Disease of the Ministry of Health, Labor and Welfare (MHLW), Japan. The committee completed a systematic review of evidences for several clinical questions and developed CPG for SS 2017 according to the procedure proposed by the Medical Information Network Distribution Service (Minds). The recommendations and their strength were checked by the modified Delphi method. The CPG for SS 2017 has been officially approved by both Japan College of Rheumatology and the Japanese Society for SS. RESULTS: The CPG committee set 38 clinical questions for clinical symptoms, signs, treatment, and management of SS in pediatric, adult and pregnant patients, using the PICO (P: patients, problem, population, I: interventions, C: comparisons, controls, comparators, O: outcomes) format. A summary of evidence, development of recommendation, recommendation, and strength for these 38 clinical questions are presented in the CPG. CONCLUSION: The CPG for SS 2017 should contribute to improvement and standardization of diagnosis and treatment of SS.
29766809 Associations between Depressive Disorders and Inflammatory Rheumatic Diseases. 2018 Depressive disorders, are not only common but also among the leading causes of disability worldwide. They are associated with increased incidences of various other diseases. It has been shown that in patients with autoimmune diseases, when depression coexists, the quality of life is worse and medical treatment and management is compromised. Depression-like symptoms, such as fatigue and disinterest are also common in inflammatory rheumatic diseases and often associated with poor quality of life. Medical therapy targeting inflammation results in alleviation of these symptoms in many patients. Interestingly, there is cumulating evidence suggesting potential roles of inflammatory cytokines in the pathogenesis of major depression. Effects of some of the biological agents used in rheumatic diseases have been studied on depressive disorders. Results have been controversial and further studies are needed in this area. These findings suggest associations between depression and inflammatory rheumatic diseases and raise the possibility that treatment of one of them might influence the outcome of the other. We have reviewed the current literature on associations between depression and inflammatory rheumatologic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome and ankylosing spondylitis.
28462679 Thumb boutonnière deformity without rheumatoid arthritis or trauma. 2018 Mar Boutonnière deformity of the thumb without rheumatoid arthritis or trauma is not widely recognised. This study aimed to investigate its prevalence, relation to sex and age, and identifying factors associated with the extensor mechanism using ultrasonography. We examined 248 thumbs from 127 participants who were asymptomatic for hand disorders and had no history of hand injury. Boutonnière deformity was identified in 20 thumbs of 17 participants and was significantly more prevalent among elderly participants than among young participants. No significant differences in sex or hand dominance were noted. The deformity had a significant effect on range of motion and grip and pinch strengths. The extensor pollicis brevis (EPB) tendon was significantly narrower in affected thumbs than in non-affected thumbs. The prevalence of boutonnière deformity without rheumatoid arthritis or trauma was 13%, and the deformity was associated with advanced age and a narrow EPB tendon. LEVEL OF EVIDENCE: III.
30108447 Intervention of integrative medicine treatment has impact on serum levels of ET-1, TNF-α, 2018 Jul Rheumatoid arthritis (RA) is a systemic autoimmune disease that can destroy peripheral joints. However, very little is known regarding specific biological marker for RA in Chinese patients. In this study, we determined the serum biomarkers and clinical features of RA-CVD. We also evaluated the short-term efficacy of routine RA treatment combined with integrative medicine treatment on RA-CVD. We found that anti-cyclic citrullinated peptide (CCP) and disease activity score in 28 joints (DAS28) are associated with risks of cardiovascular disease (CVD) in RA. And, melatonin (MLT) may play a negative regulatory role in cardiovascular damage in patients with RA. Furthermore, endothelin (ET-1) and inflammatory markers may be subclinical cardiovascular damages in RA. Moreover, of the 17 patients with RA-CVD, test results of ET-1, TNF-α and OSCAR after integrative medicine treatment were significantly decreased than before treatment. Collectively, our results provide a therapeutic potential of integrative medicine to the treatment of RA-CVD.
29947426 Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer. 2018 Aug Ectopic (or tertiary) lymphoid structures (ELS) are organized aggregates of lymphocytes resembling secondary lymphoid organs and developing in chronically inflamed nonlymphoid tissues during persistent infections, graft rejection, autoimmune conditions, and cancer. In this review, we will first depict the mechanisms regulating ELS generation, focusing on the role played by lymphoid chemokines. We will then characterize ELS forming in target organs during autoimmune conditions, here exemplified by rheumatoid arthritis, and cancer, highlighting the relevance of the tissue-specific factors. Finally, we will discuss the clinical significance of ELS and the therapeutic potential of their inhibition and/or enhancement depending on the disease considered.