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ID PMID Title PublicationDate abstract
31921102 More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis. 2019 Monocyte chemoattractant protein-1 (MCP-1/CCL2) is renowned for its ability to drive the chemotaxis of myeloid and lymphoid cells. It orchestrates the migration of these cell types both during physiological immune defense and in pathological circumstances, such as autoimmune diseases including rheumatoid arthritis and multiple sclerosis, inflammatory diseases including atherosclerosis, as well as infectious diseases, obesity, diabetes, and various types of cancer. However, new data suggest that the scope of CCL2's functions may extend beyond its original characterization as a chemoattractant. Emerging evidence shows that it can impact leukocyte behavior, influencing adhesion, polarization, effector molecule secretion, autophagy, killing, and survival. The direction of these CCL2-induced responses is context dependent and, in some cases, synergistic with other inflammatory stimuli. The involvement of CCL2 signaling in multiple diseases renders it an interesting therapeutic target, although current targeting strategies have not met early expectations in the clinic. A better understanding of how CCL2 affects immune cells will be pivotal to the improvement of existing therapeutic approaches and the development of new drugs. Here, we provide an overview of the pleiotropic effects of CCL2 signaling on cells of the myeloid lineage, beyond chemotaxis, and highlight how these actions might help to shape immune cell behavior and tumor immunity.
31154408 Canadian Rheumatology Association Meeting Fairmont The Queen Elizabeth Montreal, Quebec, C 2019 Jun 1 The 73rd Annual Meeting of The Canadian Rheumatology Association was held at the Fairmont The Queen Elizabeth, Montreal, Quebec, Canada February 27 - March 2, 2019. The program consisted of presentations covering original research, symposia, awards, and lectures. Highlights of the meeting include the following 2019 Award Winners: Distinguished Rheumatologist, Edward Keystone; Distinguished Investigator, Diane Lacaille; Teacher-Educator, Shirley Tse; Emerging Investigator, Glen Hazlewood; Best Abstract on SLE Research by a Trainee - Ian Watson Award, Alexandra Legge; Best Abstract on Clinical or Epidemiology Research by a Trainee - Phil Rosen Award, Lauren King; Best Abstract on Basic Science Research by a Trainee, Remy Pollock; Best Abstract for Research by an Undergraduate Student, Andrea Carboni-Jimènez; Best Abstract on Research by a Rheumatology Resident, May Choi; Best Abstract by a Medical Student, Leonardo Calderon; Best Abstract by a Post-Graduate Research Trainee, Carolina Munoz-Grajales; Best Abstract by a Rheumatology Post-Graduate Research Trainee, Andre Luquini; Best Abstract on Quality Care Initiatives in Rheumatology, Cheryl Barnabe and Ines Colmegna; Best Abstract on Research by Young Faculty, Bindee Kuriya; Practice Reflection Award, Gold, Jason Kur; Practice Reflection Award, Silver, May Choi. Lectures and other events included Keynote Lecture by Andre Picard: Quirky Past, Uncertain Future: The State of Medicare in Canada; Keynote Address by Diane Lacaille, Distinguished Investigator Awardee: Time to Re-Label Comorbidities in RA - Coexisting or Complications; State of the Art Lecture by Mark Roberts: Myositis and its Mimics; Dunlop-Dottridge Lecture by Gilles Boire: The 4-H of Biomarkers in Arthritis: A lot of Help, Potential Harm, Some Hype, Increasing Hope; and the Great Debate: Be it Resolved that Competency-based Medical Education will Result in Improved Quality of Care for Patients vs the "Old Way" of Training Rheumatologists. Arguing for: Mercedes Chan and Marie-Paule Morin, and against: Beth Hazel and Heather McDonald-Blumer. Topics including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, psoriatic arthritis, spondyloarthritis, vasculitis, osteoarthritis, fibromyalgia, and their respective diagnoses, treatments, and outcomes are reflected in the abstracts, which we are pleased to publish in this issue of The Journal.
30804784 The Regulatory Effects of Paeoniflorin and Its Derivative Paeoniflorin-6'-O-Benzene Sulfon 2019 The plant extract "total glucosides of peony" (TGP) constitutes a mixture of glycosides that is isolated from the roots of the well-known traditional Chinese herb Paeonia lactiflora Pall. Paeoniflorin (Pae) is the most abundant component and the main biologically active ingredient of TGP. Pharmacologically, Pae exhibits powerful anti-inflammatory and immune regulatory effects in some animal models of autoimmune diseases including Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). Recently, we modified Pae with an addition of benzene sulfonate to achieve better bioavailability and higher anti-inflammatory immune regulatory effects. This review summarizes the pharmacological activities of Pae and the novel anti-inflammatory and immunomodulatory agent Paeoniflorin-6'-O-benzenesulfonate (CP-25) in various chronic inflammatory and autoimmune disorders. The regulatory effects of Pae and CP-25 make them promising agents for other related diseases, which require extensive investigation in the future.
30199605 Advances and challenges in targeting IRF5, a key regulator of inflammation. 2019 May Interferon regulatory factor 5 (IRF5) belongs to a family of transcription factors, originally implicated in antiviral responses and interferon production. However, studies conducted in different laboratories over the last decade have placed IRF5 as a central regulator of the inflammatory response. It has become clear that IRF5 contributes to the pathogenesis of many inflammatory and autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus. Given the role of IRF5 in physiology and disease, IRF5 represents a potential therapeutic target. However, despite a significant interest from the pharmaceutical industry, inhibitors that interfere with the IRF5 pathway remain elusive. Here, we review the advances made by various studies in targeting multiple steps of signalling leading to IRF5 activation with their therapeutic potential, and the possible complications of such strategies are discussed.
30510070 LACC1 Regulates TNF and IL-17 in Mouse Models of Arthritis and Inflammation. 2019 Jan 1 Both common and rare genetic variants of laccase domain-containing 1 (LACC1, previously C13orf31) are associated with inflammatory bowel disease, leprosy, Behcet disease, and systemic juvenile idiopathic arthritis. However, the functional relevance of these variants is unclear. In this study, we use LACC1-deficient mice to gain insight into the role of LACC1 in regulating inflammation. Following oral administration of Citrobacter rodentium, LACC1 knockout (KO) mice had more severe colon lesions compared with wildtype (WT) controls. Immunization with collagen II, a collagen-induced arthritis (CIA) model, resulted in an accelerated onset of arthritis and significantly worse arthritis and inflammation in LACC1 KO mice. Similar results were obtained in a mannan-induced arthritis model. Serum and local TNF in CIA paws and C. rodentium colons were significantly increased in LACC1 KO mice compared with WT controls. The percentage of IL-17A-producing CD4(+) T cells was elevated in LACC1 KO mice undergoing CIA as well as aged mice compared with WT controls. Neutralization of IL-17, but not TNF, prevented enhanced mannan-induced arthritis in LACC1 KO mice. These data provide new mechanistic insight into the function of LACC1 in regulating TNF and IL-17 during inflammatory responses. We hypothesize that these effects contribute to immune-driven pathologies observed in individuals carrying LACC1 variants.
31346842 Correction to: Differing X-ray patterns in seronegative and seropositive rheumatoid arthri 2019 Sep The first and family names of the authors were interchanged and are now presented correctly. The original article has been corrected.
31079426 Ten-Year Results of Reconstruction for Rheumatoid Cervical Spine Lesions and Occurrence Fa 2019 Oct STUDY DESIGN: Retrospective chart review. PURPOSE: This study evaluated long-term surgical outcomes of computer-assisted reconstruction using transarticular or cervical pedicle screws for cervical spine lesions caused by advanced rheumatoid arthritis (RA). OVERVIEW OF LITERATURE: We routinely employ C1-C2 transarticular and cervical pedicle screw instrumentation to reconstruct advanced and unstable RA cervical lesions. However, few reports are available on the long-term results of surgical reconstruction for rheumatoid cervical disorders, particularly regarding cervical pedicle screw fixation. METHODS: Six subjects (all female) with RA cervical lesions who underwent atlantoaxial or occipitocervical fixation and were followed for at least 10 years were retrospectively studied. A frameless, stereotactic, optoelectronic, computed tomography-based image guidance system was used for correct screw placement. Variables including the Japanese Orthopaedic Association score, EuroQol, Ranawat value, and C2-C7 angle before and 2, 5, and 10 years after surgery were assessed along with the occurrence of subaxial subluxation (SAS). RESULTS: Mean age at initial surgery was 58.2±7 years (range, 51-68 years), and mean follow-up period was 141±11 months (range, 122-153 months). Lesions included atlantoaxial subluxation (AAS, n=2) and AAS+vertical subluxation (n=4). Mean C2-C7 lordotic angle before and 2, 5, and 10 years after surgery was 20.1°±6.1°, 21.0°±4.0°, 18.8°±4.7°, and 17.8°±5.3°, respectively. SAS did not occur in cases maintaining the C2-C7 lordotic angle. In two cases where the C2-C7 lordotic angle declined from 5 years postoperatively, SAS occurred at the C2-C3 level in one and at the C4-C5 level in the other, both of which required reoperation. CONCLUSIONS: Patients with rheumatoid cervical lesions who undergo atlantoaxial or occipitocervical fixation using C1-C2 transarticular or pedicle screws carry a risk of SAS for up to 10 years postoperatively, which may require reoperation.
31828445 Correction to: In vivo imaging of early stages of rheumatoid arthritis by α5β1-integrin- 2019 Dec 11 Following publication of the original article [1], the authors have reported an error in the 'Histopathology' (under 'Materials and methods') section of the article that compromises the reproducibility of the paper.
30740359 Progression on Citrullination of Proteins in Gastrointestinal Cancers. 2019 The citrullination modification (Cit) of proteins has received increasing attention in recent years. This kind of protein modification was first discovered in autoimmune diseases such as rheumatoid arthritis. The citrullination modification process is catalyzed by the peptidyl arginine deiminases (PADIs) family. A well-known citrullination of histone involves the key mechanism of neutrophil extracellular traps (NETs) of inflammation in the peripheral blood. Further studies revealed that citrullination modification of proteins also involves in carcinogenesis in human being. Citrullinated proteins disturbed the stability of proteins and caused DNA damages. There is increasing evidence that citrullinated proteins can be used as potential targets for cancer diagnosis or treatment. This review introduces the concept of citrullination modification of proteins, substrate proteins, examining methods and biological significances.
32042838 Fulminant Liver Failure due to Hepatitis B Reactivation During Treatment With Tocilizumab. 2019 Dec Tocilizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor that is frequently used for the treatment of refractory rheumatoid arthritis. Since patients with hepatitis B virus (HBV) infection were excluded from pivotal trials, the risk of HBV reactivation with this novel drug class remains uncertain. We present the first case of tocilizumab-associated HBV reactivation resulting in fulminant hepatic failure and a need for liver transplant. Our findings underscore the need for prophylactic antiviral therapy in patients being treated with novel immunosuppressive agents.
31396157 Modulatory Effects of Plant Polyphenols on Bone Remodeling: A Prospective View From the Be 2019 During the past, a more comprehensive knowledge of mechanisms implicated in bone resorption processes has driven researchers to develop a compound library of many small molecules that specifically interfere with the genesis of osteoclast precursors cells. Natural compounds that suppress osteoclast commitment may have therapeutic value in treating pathologies associated with bone resorption like osteoporosis, rheumatoid arthritis, bone metastasis, and periodontal disease. The present review is focused on the current knowledge on the polyphenols derived from plants that could be efficacious in suppressing osteoclast differentiation and bone resorption.
31864144 Evaluation of salivary gland fat fraction values in patients with primary Sjögren's syndr 2020 Feb PURPOSE: To explore the role of salivary fat fraction (FF) values in evaluating patients with primary Sjögren's syndrome (pSS). MATERIAL AND METHOD: A total of 28 patients with pSS, ten patients with suspected pSS, and 28 volunteers were enrolled. The FF values of the parotid and submandibular glands were generated from mDIXON Quant. A one-way analysis of variance was used to compare the FF values among the groups. A receiver-operating characteristic analysis was applied to assess the diagnostic performance of the parotid and submandibular FF values in distinguishing patients with pSS from non-pSS subjects. In particular, we focused on distinguishing patients with grade 0 pSS from those with suspected pSS. RESULTS: The parotid and submandibular mean FF value of patients with pSS was significantly higher than that of healthy volunteers. The submandibular mean FF value of patients with pSS was higher than those suspected ones. Submandibular FF value performed better than parotid FF value in differentiating patients with pSS from those non-pSS subjects (area under the curve [AUC] = 0.927 vs. 0.734), patients with pSS from patients with suspected pSS (AUC = 0.907 vs. 0.725). This value also performed better at distinguishing patients with grade 0 pSS from those patients with suspected pSS (AUC = 0.925 vs. 0.783). CONCLUSIONS: The salivary gland FF value, especially the submandibular gland FF value, distinguished patients with pSS from those patients with suspected pSS and healthy volunteers.
30136608 HLA-DQB1 DPB1 alleles in Japanese patients with adult-onset Still's disease. 2019 Sep Objective: HLA class II alleles are major determinants of genetic predisposition to rheumatic diseases. Predisposing effects of HLA had been suggested in AOSD, however, ethnic differences may account for variations in AOSD association with HLA. We determined the contribution of HLA-DQB1, DPB1 alleles to susceptibility to Adult-onset Still's disease (AOSD) in the Japanese population. Methods: HLA-DQB1 and DPB1 alleles were analyzed in 87 Japanese patients with AOSD and 413 Japanese healthy subjects. Results: We found significant association between HLA-DQB1*06:02 (Pc = 0.010, odds ratio: 2.54) and AOSD, whereas there was no association between the DQB1*06:02 allele and disease phenotypes of AOSD. Moreover, we did not find a predisposing effect of the HLA-DPB1 allele to AOSD. Haplotype analysis showed that presence of DRB1*15:01-DQB1*06:02 was associated with Japanese patients with AOSD. However, conditional logistic regression tests were unable to demonstrate independent association between DRB1*1501 or DQB1*0602 and AOSD. Conclusions: Our results show significant association between AOSD and the HLA DQB1*06:02 allele, and between the DRB1*1501-DQB1*06:02 haplotype and AOSD susceptibility. These findings suggest that genetic susceptibility to AOSD depends on the genotype combinations of HLA DRB1 and DQB1 alleles.
31440029 Remicade(®) (infliximab): 20 years of contributions to science and medicine. 2019 On August 24, 1998, Remicade(®) (infliximab), the first tumor necrosis factor-α (TNF) inhibitor, received its initial marketing approval from the US Food and Drug Administration for the treatment of Crohn's disease. Subsequently, Remicade was approved in another five adult and two pediatric indications both in the USA and across the globe. In the 20 years since this first approval, Remicade has made several important contributions to the advancement of science and medicine: 1) clinical trials with Remicade established the proof of concept that targeted therapy can be effective in immune-mediated inflammatory diseases; 2) as the first monoclonal antibody approved for use in a chronic condition, Remicade helped in identifying methods of administering large, foreign proteins repeatedly while limiting the body's immune response to them; 3) the need to establish Remicade's safety profile required developing new methods and setting new standards for postmarketing safety studies, specifically in the real-world setting, in terms of approach, size, and duration of follow-up; 4) the study of Remicade has improved our understanding of TNF's role in the immune system, as well as our understanding of the pathophysiology of a range of diseases characterized by chronic inflammation; and 5) Remicade and other TNF inhibitors have transformed treatment practices in these chronic inflammatory diseases: remission has become a realistic goal of therapy and long-term disability resulting from structural damage can be prevented. This paper reviews how, over the course of its development and 20 years of use in clinical practice, Remicade was able to make these contributions.
31198690 Molecular Interaction Network Approach (MINA) identifies association of novel candidate di 2019 Molecular Interaction Network Approach (MINA) was used to elucidate candidate disease genes. The approach was implemented to identify novel gene association with commonly known autoimmune diseases [1]. In MINA, we evaluated the hypothesis that "network proximity" within a whole genome molecular interaction network can be used to inform the search for multigene inheritance. There are now numerous examples of gene discoveries based upon network proximity between novel and previously identified disease genes (Yin et al., 2017 [2], Wang et al., 2011 [3], and Barrenas et al., 2009 [4]). This study extends the application of interaction networks to the interrogation of Genome Wide Association studies: first, by showing that a group of nine autoimmune diseases (AuD) genes "seed genes", are connected in a highly non-random manner within a whole genome network; and second, by showing that the minimal number of connecting genes required to connect a maximal number of AuD candidate genes are highly enriched as candidate genes for AuD predisposing mutations. The findings imply that a threshold number of candidate genes for any heritable disorder can be used to "seed" a molecular interaction network that •Serves to validate the disease status of closely associated seed genes•Identifies genes that are highly enriched as novel candidate disease genes•Provides a strategy for elucidation of epistatic gene x gene interactions The method could provide a critical toll for understanding the genetic architecture of common traits and disorders.
31118865 Casual effect of methotrexate+etanercept/infliximab on survival of patients with rheumat 2019 Background and objectives: Following the discovery of new drugs, physicians and pharmaceutical companies have become interested in examining patients' mortality and morbidity rates. In this respect, the effects of methotrexate (MTX)+etanercept/infliximab (ETA/INF) therapy on the survival of rheumatoid arthritis patients (RA) were evaluated in this study using marginal structural piecewise constant baseline hazard model. Patients and methods: According to the standard protocol, MTX is considered as the first-line treatment for RA patients. If there is no adequate response to MTX, biologic drugs will be added. To compare the survival rates of RA patients in MTX- and MTX+ETA/INF-treated groups, the piecewise constant baseline hazard model was fitted. Then, due to the existence of the time-dependent confounder (VAS) which was affected by previous treatment, the weight for each person-time was calculated via the inverse probability treatment weighting method. These weights were then used by marginal structural piecewise constant baseline hazard model. Finally, these models were compared. Results: The median (IQR) of the follow-up period in patients receiving MTX+ETN/INF and MTX was 11 (15.25) and 11 (31), respectively, and the 8-year survival rate was reported by 70% versus 68%, respectively. First, the piece-wise constant baseline hazard model was fitted. Fitting the given model showed that MTX+ETA/INF had a significant effect on patients' survival (HR=0.789, 95% CI [0.634, 0.983]). Second, marginal structural piecewise constant baseline hazard model was fitted. But, the results of this model revealed that MTX+ETA/INF did not have a significant impact on patients' survival (HR=0.968, 95% CI [0.860, 1.090]). Conclusion: Adjusting the pain score over time as a time-dependent confounder via marginal structural piecewise constant baseline hazard model, it has been demonstrated that MTX+ETA/INF does not have a significant effect on patients' survival rates. Therefore, a significant difference can be found between survival rates of these groups using longitudinal studies.
31308768 Frequency of sleep disorders in patients with rheumatoid arthritis. 2019 Purpose: To determine the prevalence of common sleep problems among patients with rheumatoid arthritis (RA) and their relationship with the disease activity and quality of life. Patients and methods: The study sample consisted of 101 patients who attended a rheumatology clinic at a university hospital between October 2015 and May 2016. All subjects were clinically examined and interviewed by physicians using a questionnaire. The collected information included sociodemographic characteristics, the patients' medical histories, the Disease Activity Score (DAS28), the Berlin questionnaire to assess the risk of obstructive sleep apnea (OSA), the Epworth Sleepiness Scale to assess excessive daytime sleepiness (EDS), the Athens Insomnia Scale to assess insomnia, the International RLS Study Group score to diagnose restless legs syndrome (RLS), and the Health Assessment Questionnaire (HAQ) to assess the quality of life. Results: The mean age of the participants was 48.7±14.6 years, and 95% of the participants were females. Approximately 60% of the participants were in the remission/low category of disease activity, and the average DAS28 score was 3.3±0.8 years. The prevalence rates of insomnia, EDS, sleep disturbance, risk of OSA, and RLS were 63%, 20%, 20%, 37%, and 63%, respectively. Furthermore, the distribution of sleep disorders was not affected by the disease activity. The association between the HAQ and sleep disorders among the RA patients was not significant. Conclusion: Sleep disorders are common among RA patients and may require further attention by treating clinicians; nevertheless, these disorders are not associated with disease activity and do not affect the quality of life.
31875749 Treatment of serologically negative Sjögren's syndrome with tacrolimus: A case report. 2020 Apr We herein report an unusual case of primary Sjögren's syndrome in a 38-year-old woman with typical clinical symptoms (joint pain, dry mouth, and positive Schirmer test) and immunoglobulin G positivity but negativity for antinuclear antibody and all antinuclear antibody spectrum antibodies. Emission computed tomography demonstrated normal ingestion but impaired secretion by the submandibular and bilateral parotid glands. Labial gland biopsy revealed chronic tissue inflammatory changes and Chisholm grade 4 lymphocyte infiltration, confirming primary Sjögren's syndrome. The patient's condition was successfully controlled by nonsteroidal treatment with tacrolimus. Patients presenting with chronic dry mouth should be examined by a Schirmer test, lip gland biopsy, and salivary gland emission computed tomography for possible Sjögren's syndrome, even if serological autoantibodies are negative, to facilitate early intervention. Tacrolimus is a potential treatment option in patients intolerant of steroidal drugs.
31875742 Ileocecal junction perforation by colonic T-cell lymphoma in a patient with primary Sjögr 2020 Apr Primary Sjögren's syndrome (pSS) is associated with an increased risk of lymphoma, especially non-Hodgkin's lymphoma. The rarest pathological subtype is T-cell lymphoma. We herein report a case of a 52-year-old man with a 17-year history of pSS who was admitted to our hospital with chronic epigastric pain and a positive fecal occult blood test. Colonoscopy revealed multiple colonic ulcers, and histological and immunological studies demonstrated the T-cell origin of this lymphoma. However, the patient rejected all treatments. He developed recurrent intestinal obstruction and infection for 3 years until an intestinal perforation occurred. The right half of the colon was resected and colostomy was performed. However, the patient died of an intestinal fistula and intraperitoneal infection 40 days postoperatively. This case highlights the rarity of the correlation between T-cell lymphoma and pSS.
31365336 The role of low density granulocytes and NETosis in the pathogenesis of adult-onset Still' 2019 Nov OBJECTIVES: To analyse the potential contribution of low-density granulocytes (LDGs) and NETosis, as well as the differential protein cargo of neutrophil extracellular traps (NETs), as physiopathogenic mechanisms of adult-onset Still's disease (AOSD). METHODS: We recruited 30 patients with AOSD according to the Yamaguchi diagnostic criteria. LDGs were addressed by multiparametric flow cytometry as those CD14-, CD15+, CD10+ cells in the peripheral blood mononuclear cells fraction. NETs were quantified by ELISA, immunofluorescence and fluorescence spectrometry. The expression of LL-37 and high mobility group box 1 (HMGB-1) in NETs was measured by immunofluorescence and confocal microscopy. Additionally, normal density neutrophils from healthy controls were stimulated with serum from patients with AOSD and NET induction was assessed by immunofluorescence. RESULTS: Patients with active disease as well as those with arthritis, cutaneous manifestations and fever had a higher amount of NETs and LDGs. Serum NETs from AOSD patients correlated with the number of swollen joints (r=0.41, p=0.032), absolute number of monocytes (r=0.529, p=0.005). The spontaneous NETs from patients with cutaneous manifestations and fever had higher cargo of HMGB-1 compared with patients in remission. CONCLUSIONS: LDGs and NETs are increased in patients with active AOSD and correlate with particular clinical features. Patients with cutaneous lesions and fever present a higher cargo of HMGB1 in their spontaneous NETs.