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ID PMID Title PublicationDate abstract
34859414 A Case of Thoracolithiasis Extracted with a Thoracoscope. 2021 Dec 20 We report on an 81-year-old male patient in whom chest computed tomography during follow-up for extramammary Paget's disease revealed a nodule in the right thoracic cavity. Because he had been taking methotrexate for rheumatoid arthritis, the possibility of methotrexate-associated lymphoproliferative lung disease was considered and methotrexate was discontinued as a precaution. No calcification was found inside the nodule, and there was no change in its size or position for 6 months. The patient had a history of malignant tumor, so thoracoscopic surgery was performed for diagnostic purposes. A free white nodule was found in the right thoracic cavity and was subsequently removed. The pathological diagnosis was thoracolithiasis; although the nodule had not moved since its discovery, movement was suspected to have occurred 3 years prior. Although thoracolithiasis is rare, it should be considered as a differential diagnosis for nodules at the end of the lung field and on the diaphragm.
34334364 Autoantibodies Against Unmodified and Citrullinated Human Endogenous Retrovirus K Envelope 2022 Jan OBJECTIVE: Autoantibodies against proteins encoded by human endogenous retrovirus K (HERV-K) have been reported in patients with rheumatoid arthritis (RA), but their relevance, if any, has remained unresolved. We revisited this question and tested if such autoantibodies may react with citrullinated epitopes on the envelope (Env) protein of HERV-K. METHODS: Immunoblotting and ELISAs were conducted with unmodified Env protein and with Env citrullinated by protein arginine deiminase 4 (PAD4). Sera from 100 patients with RA, plasma from 32 patients with juvenile idiopathic arthritis (JIA), and healthy adult and pediatric controls were included. Antibody reactivity was evaluated for correlations with clinical and laboratory variables of the patients. RESULTS: We replicated and expanded upon published data suggesting that patients with RA or JIA have autoantibodies against HERV-K Env, some with high titers. Anti-HERV-K antibodies correlated with cigarette smoking and with circulating myeloperoxidase-DNA complexes indicative of nonapoptotic neutrophil cell death. Further, most of the patients with RA, but not those with JIA, had autoantibodies that reacted more strongly with Env that was citrullinated by PAD4. These anticitrullinated Env autoantibodies correlated with seropositivity and tended to be higher in patients with erosive disease. CONCLUSION: Our data suggest that anti-HERV-K immunity is elevated in RA and JIA and may have a connection with pathogenic protein citrullination in RA.
33006176 Paeoniflorin-6'-o-benzene sulfonate (CP-25) improves vasculitis through inhibiting IL-17A/ 2021 Feb Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.
32928740 Factors associated with progression to inflammatory arthritis in first-degree relatives of 2021 Feb OBJECTIVES: Little is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting. METHODS: We screened for serum cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor isotype aAbs in subjects who were at increased risk for rheumatoid arthritis (RA) because they are a first-degree relative of an individual with classified RA (n=1780). We evaluated combinations of aAbs and high titre aAbs, as defined by 2-times (2 x) the standard cut-off and an optimal cut-off, as predictors of our two outcomes, aAb+ persistence and incident IA. RESULTS: 304 subjects (17.1%) tested aAb+; of those, 131 were IA-free and had at least one follow-up visit. Sixty-four per cent of these tested aAb+ again on their next visit. Anti-CCP+ at levels ≥2 x the standard cut-off was associated with 13-fold higher likelihood of aAb +persistence. During a median of 4.4 years (IQR: 2.2-7.2), 20 subjects (15.3%) developed IA. Among subjects that screened anti-CCP+ at ≥ 2 x or ≥an optimal cut-off, 32% and 26% had developed IA within 5 years, respectively. Both anti-CCP cut-offs conferred an approximate fourfold increased risk of future IA (HR 4.09 and HR 3.95, p<0.01). CONCLUSIONS: These findings support that aAb screening in a non-clinical setting can identify RA-related aAb+ individuals, as well as levels and combinations of aAbs that are associated with higher risk for future IA. Monitoring for the development of IA in aAb+ individuals and similar aAb testing approaches in at-risk populations may identify candidates for prevention studies in RA.
33863926 Functional disability is related to serum chemerin levels in rheumatoid arthritis. 2021 Apr 16 Adipokines, especially chemerin, can interact with cytokines and other molecules in inflammation. To date, there is insufficient information regarding a possible correlation between functional disability and chemerin and other pro-inflammatory molecules in rheumatoid arthritis (RA). To identify the association of functional disability with serum chemerin and other pro-inflammatory molecules, including other adipokines, cytokines and E-selectin, in patients with RA. Cross-sectional study. Assessment: disease activity (DAS28-ESR) and functional disability (HAQ-DI). We compared the adipokines (chemerin, leptin, adiponectin, resistin, and visfatin), cytokines (TNF-α, IL-6, IL-1β, and IL-18) and E-selectin levels between RA with functional disability and RA non-disabled patients. Of 82 patients with RA, 43 (52%) had functional disability. The RA with functional disability group had higher chemerin (140 vs. 112 ng/mL, p = 0.007) than the non-disabled RA group. Chemerin correlated with the HAQ-DI (rho = 0.27, p = 0.02) and DAS28-ESR (rho = 0.21, p = 0.05). Severe activity correlated with IL-6 (rho = 0.33, p = 0.003) and E-selectin (rho = 0.23, p = 0.03) but not with disability. No other pro-inflammatory molecules correlated with HAQ-DI. High chemerin levels were associated with functional disability in RA, whereas no other molecules correlated with loss of function. These results encourage further studies assessing new roles of chemerin as a marker of impairment in RA.
34193085 Mortality rate in rheumatoid arthritis-related interstitial lung disease: the role of radi 2021 Jun 30 BACKGROUND: To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. METHODS: A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. RESULTS: 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4-104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4-4.17]. Women of 60-75 years of age were the group with the highest SMR. CONCLUSIONS: RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.
33470051 A patient-centered knowledge translation tool for treat-to-target strategy in rheumatoid a 2021 Mar AIM: Implementation of treat-to-target (T2T) for rheumatoid arthritis (RA) presents many challenges and an evidence-practice gap has emerged. This study assessed clinician and patient barriers to the implementation of an RA-T2T strategy and developed a knowledge translation (KT) tool for use in "real-life" clinical settings. METHODS: Surveys of patients and rheumatologists measured agreement with RA-T2T recommendations and use in daily practice. Patient knowledge and perceptions were assessed as was clinician willingness to alter practice and barriers to RA-T2T using visual analog scales. An electronic KT-tool was developed and a two-phase usability trial undertaken to assess use in clinical interactions. RESULTS: Ninety-one percent of patients had no prior knowledge of RA-T2T but agreed with the recommendations showing mean level agreement scores (8.39-9.54, SD 2.37-1.54). Ninety percent were willing to try RA-T2T, 49% felt their treatment could be improved and 28% wanted more involvement in treatment decisions. Rheumatologists agreed with RA-T2T recommendations (7.30-9.27, SD 2.59-0.91). Barriers to implementation identified by rheumatologists included time, appointment availability and perceived patient reluctance to escalate medications. Usability experiences with the KT-tool were tracked and clinicians reported it was easy to use (100%), resulted in a discussion of RA-T2T (73%) and a target being set for 63% of consults. Patients reported they read (92%) and understood (87%) the information in the KT-tool, and that a target was set in 62% of interactions. CONCLUSIONS: RA-T2T uptake in clinical practice may be improved through understanding local clinician and patient barriers and an implementation strategy utilizing a patient-driven KT-tool.
33807259 Symmetry Criterion for Patients with Rheumatoid Arthritis of the Foot: A Cross-Sectional S 2021 Mar 31 OBJECTIVE: The aim of the study was to analyze the feet of rheumatoid arthritis (RA) patients, to determine the degree to which both feet were affected, primarily analyzing the severity of RA in both feet looking at structure and morphology, and secondly looking at the symmetry in terms of the anthropometrics and posture. METHOD: This cross-sectional study was conducted from January to December 2018. The data from 229 patients with RA and with foot pain and no RA recruited (Granada, Spain) were analyzed. Two researchers independently interviewed the patients to obtain the study data. The clinical data were obtained using specific foot health and quality of life questionnaires and a validated platform for foot measurement. Anthropometric measurements were obtained by means of a foot measurement platform and the Foot Posture Index (FPI). The bivariate analysis was performed with the Student's t test and the non-parametric Wilcoxon test. The level of significance was established at p < 0.05. RESULTS: In the RA group, anthropometric measurements revealed significant differences between the left and right feet in 13 of the 23 parameters considered, as follows: (non-load-bearing) foot length, length of the first metatarsophalangeal joint, maximum height of the internal longitudinal arch, and width of the midfoot (p < 0.001, p = 0.038, p < 0.001, and p = 0.037 respectively); and Foot Posture Index (p = 0.001). CONCLUSIONS: In patients with RA, statistically significant differences were found in the Foot Posture Index and in several parameters related to foot structure and morphology. From this, we conclude that from a morphological, structural, and postural standpoint, a pattern of symmetric joint involvement should not be viewed as a specific criterion for RA in the foot.
34267065 Elevated serum Dickkopf-1 is a biomarker for bone erosion in patients with psoriatic arthr 2021 Jul 15 BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients. METHODS: Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA. RESULTS: Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246-15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA. CONCLUSIONS: The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.
34187325 Arthritis-associated osteoclastogenic macrophages (AtoMs) participate in pathological bone 2022 Mar Rheumatoid arthritis is a chronic form of arthritis that causes bone destruction in joints such as the knees and fingers. Over the past two decades, the clinical outcomes of rheumatoid arthritis have improved substantially with the development of biological agents and Janus kinase inhibitors. Osteoclasts are myeloid lineage cells with a unique bone-destroying ability that can lead to joint destruction. On the other hand, osteoclasts play an important role in skeletal homeostasis by supporting bone remodeling together with osteoblasts in the bone marrow under steady-state conditions. However, the same osteoclasts are considered to participate in physiological bone remodeling and joint destruction. We found that pathological osteoclasts have different differentiation pathways and regulatory transcription factors compared to physiological osteoclasts. We also identified arthritis-associated osteoclastogenic macrophages (AtoMs), which are common progenitors of pathological osteoclasts in mice and humans that develop specifically in inflamed synovial tissue. This review presents details of the newly identified AtoMs and the original intravital imaging systems that can visualize synovial tissue and pathological osteoclasts at the pannus-bone interface.
34525234 Treatment of palindromic rheumatism: A systematic review. 2021 Nov OBJECTIVES: Palindromic rheumatism (PR) characterised by self-resolving attacks of arthritis and peri-arthritis that may progress to other autoimmune connective tissue diseases (CTDs). The aim of this systematic review was to analyse the effectiveness of different treatments on PR. METHODS: Articles were collected from Cochrane, PubMed, Science Direct, Scopus, ProQuest, Ebsco, Google Scholar, MEDLINE and EMBASE. Search keywords were "palindromic rheumatism," "palindromic rheumatism and remission," "palindromic rheumatism and course," "palindromic rheumatism and prognosis," "palindromic rheumatism and treatment" and "palindromic rheumatism and therapy." The studies that were included met the following criteria: (a) adult patients aged ≥16 with PR; (b) being on treatment with medications defined as those that were developed for the treatment of inflammatory arthritis and (c) including outcome measures to evaluate the efficacy of the treatment including remission rate and progression to other diseases. RESULTS: Twenty-four studies met the inclusion criteria. Although case series and retrospective studies showed that conventional disease-modifying antirheumatic drugs (DMARDs) can control attacks of the disease, 15%-70% of patients with PR evolve to autoimmune CTDs during several years, despite treatment with DMARDs. A retrospective study showed that tight control strategy could control attacks of the disease and prevent its progression to RA. The evidence provided from available studies is insufficient to determine that DMARDs can prevent the progression of PR to autoimmune CTDs. CONCLUSION: Although case series and retrospective studies showed that DMARDs can control attacks of the disease, our review suggests that randomised clinical trials and prospective studies with adequate sample size are needed to prove that DMARDs can prevent progression of PR to autoimmune CTDs and which DMARDs are preferred for the treatment of PR.
34344703 Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutati 2021 Dec OBJECTIVES: To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. METHODS: FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. RESULTS: Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. CONCLUSION: Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.
33407801 Efficacy and safety of upadacitinib over 84 weeks in Japanese patients with rheumatoid a 2021 Jan 6 BACKGROUND: The objective of the study was to evaluate the efficacy and safety of upadacitinib over 84 weeks in Japanese patients with active rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. METHODS: All patients completing a 12-week, randomized, double-blind treatment period entered a blinded extension and continued upadacitinib 7.5, 15, or 30 mg once daily (QD), or were switched from placebo to upadacitinib 7.5, 15, or 30 mg QD. Efficacy and safety were assessed over 84 weeks. RESULTS: Of 197 randomized patients, 187 (94.9%) completed the 12-week period and entered the blinded extension; 152 (77.2%) patients were ongoing at week 84. At week 84, the proportions of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) were 85.7%, 77.6%, and 58.0% with continued upadacitinib 7.5, 15, and 30 mg, respectively (nonresponder imputation), and were similar in patients who had switched from placebo. Favorable response rates were also observed for more stringent measures of response (ACR50/70) and remission (defined by the Disease Activity Score of 28 joints with C-reactive protein, Clinical Disease Activity Index, or Simplified Disease Activity Index). The 15 mg and 30 mg doses of upadacitinib were associated with more rapid and numerically higher initial responses for some measures of disease activity and remission compared with the 7.5 mg dose. Rates of adverse events, infection, opportunistic infection, serious infection, and herpes zoster were lower with upadacitinib 7.5 and 15 mg versus 30 mg. CONCLUSIONS: Upadacitinib demonstrated sustained efficacy and was well tolerated over 84 weeks in Japanese patients with RA, with upadacitinib 15 mg offering the most favorable benefit-risk profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT02720523 . Registered on March 22, 2016.
33020846 A randomized prospective open-label controlled trial comparing the performance of a connec 2021 Apr 6 OBJECTIVES: In RA, telemedicine may allow tight control of disease activity while reducing hospital visits. We developed a smartphone application connected with a physician's interface to monitor RA patients. We aimed to assess the performance of this e-Health solution in comparison with routine practice in the management of patients with RA. METHODS: A six-month pragmatic, randomized, controlled, prospective, clinical trial was conducted in RA patients with high to moderate disease activity starting a new DMARD therapy. Two groups were established: 'connected monitoring' and 'conventional monitoring'. The primary outcome was the number of physical visits between baseline and six months. Secondary outcomes included adherence, satisfaction, changes in clinical, functional and health status scores (Short-Form 12). RESULTS: Of the 94 randomized patients, 89 completed study: 44 in the 'conventional monitoring' arm and 45 in the 'connected monitoring' arm. The total number of physical visits between required baseline and six-month visits was significantly lower in the 'connected monitoring' group [0.42 (0.58) vs 1.93 (0.55); P <0.05]. No differences between groups were observed in the clinical and functional scores. A better quality of life for Short-Form 12 subscores (Role-Physical and Role-Emotional) were found in the 'connected monitoring' group. CONCLUSION: Our results suggest that connected monitoring reduces the number of physical visits while maintaining a tight control of disease activity and improving quality of life in patients with RA starting a new treatment. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03005925.
33730208 Patient perspectives on how to improve education on medication side effects: cross-section 2021 May Rheumatoid arthritis (RA) patients often report lacking information on medication side effects. The aims of this study were to observe how rheumatology healthcare providers deliver medication information and to determine in which specific domains information is missing. First, 12 single-blinded structured observations were performed during regular RA patient consultations. The observers noted whether and how medication and medication side effects were discussed. Second, 100 RA patients were asked to fill out an adaptation of the Satisfaction with Information about Medicines Scale (SIMS). Medication was discussed during all observed consultations. With new medication, its purpose and mode of action were explained in all cases, but possible side effects in only 33%. Overall, medication side effects were discussed in 58% of consultations. Most information delivery was verbal (92%). Response rate to the questionnaire was 61%. Overall satisfaction with medication education was mean 7.3 (± 1.9) (NRS 0-10) with a comparable high SIMS total satisfaction sum score of mean 12.3 (± 4.4). At subscale score levels, 89% were satisfied with the amount of information on the action and usage of medication, but only 47% with the information on the potential problems of medication. RA patients express overall high satisfaction with their medication education but there is still an unmet need for information on potential risks and side effects. Using the SIMS questionnaire in daily clinical practice may help focus medication education to the needs of the individual patient.
33899926 Lymphocyte modulation by tofacitinib in patients with rheumatoid arthritis. 2021 Aug Tofacitinib is an oral small molecule targeting the intracellular Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways approved for the treatment of active rheumatoid arthritis (RA). We investigated the effects of tofacitinib on the response of RA lymphocytes to B and T cell collagen epitopes in their native and post-translationally modified forms. In particular, peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy subjects were cultured with type II collagen peptides (T261-273, B359-369, carT261-273, citB359-369) or with phorbol myristate acetate (PMA)/ionomycin/CD40L in the presence or absence of 100 nM tofacitinib for 20 h and analyzed by fluorescence activated cell sorter (FACS). Cultures without brefeldin A were used for cytokine supernatant enzyme-linked immunosorbent assay (ELISA) analysis. Tofacitinib down-regulated inflammatory cytokines by stimulated B [interleukin (IL)-6 and tumor necrosis factor (TNF)-α] and T [interferon (IFN)-γ, IL-17 or TNF-α] cells in the short term, while a significant reduction of IL-17 and IL-6 levels in peripheral blood mononuclear cell (PBMC) supernatant was also observed. IL-10 was significantly reduced in collagen-stimulated B cells from patients with RA and increased in controls, thus mirroring an altered response to collagen self-epitopes in RA. Tofacitinib partially prevented the IL-10 down-modulation in RA B cells stimulated with collagen epitopes. In conclusion, the use of tofacitinib exerts a rapid regulatory effect on B cells from patients with RA following stimulation with collagen epitopes while not reducing inflammatory cytokine production by lymphocytes.
32656595 Localisation of citrullinated and carbamylated proteins in inflamed gingival tissues from 2021 Mar OBJECTIVES: It has been proposed that citrullination and carbamylation occur in the inflamed periodontium and could be the plausible mechanisms for the generation of antigens involved in the development and progression of RA. The purpose of this study was to determine the presence and location of citrullinated and carbamylated proteins in the gingival tissues and compare their abundance in periodontitis (PD) patients with or without RA. MATERIALS AND METHODS: Gingival tissue samples of healthy (n = 5), PD with RA (n = 5) and PD without RA (n = 5) were collected. Specimens were formalin fixed, paraffin embedded and sectioned at 4 μm. The tissue sections were analysed for the presence of citrullinated and carbamylated proteins by immunohistochemistry. Semi-quantitative analysis was performed to quantify and compare the protein abundance between groups. RESULTS: The number of cells containing citrullinated and carbamylated proteins with higher intensity was markedly increased in gingival tissues from PD with or without RA in comparison with healthy controls. CONCLUSION: Inflamed gingival tissue is a potential source of citrullinated and carbamylated proteins other than synovial tissues. The extent to which the local accumulation of these proteins contributes to the pathogenesis of RA needs further elucidation. CLINICAL RELEVANCE: If PD is a potential source of post-translationally modified proteins, untreated PD should not be taken lightly in the context of RA. Hence, addressing gingival inflammation should be viewed as an important preventive measure in the general population not only for the progression of periodontal disease but also reducing the risk of developing extra-oral comorbidities.
33330982 Salivary and serum concentrations of monocyte chemoattractant protein-1, macrophage inhibi 2021 Sep BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), and fractalkine are chemokines that are expressed by a variety of cell types to regulate macrophage inflammatory response. The aim of the study was to examine the effects of periodontitis and rheumatoid arthritis (RA) on their serum and salivary concentrations. METHODS: Adults with either periodontitis (P, n = 21), or with rheumatoid arthritis (RA, n = 23), or with both diseases (RA+P, n = 23) were included in the study. Systemically and periodontally healthy individuals (n = 22) served as controls. Saliva and serum samples were collected from all participants before the medical and periodontal examinations. Salivary and serum MCP-1, MIF, and fractalkine concentrations were measured by the Luminex technique. Total salivary protein levels were determined by the Bradford assay. RESULTS: Salivary MCP-1, MIF, and fractalkine concentrations were elevated in both RA groups (RA+P and RA) in comparison with systemically healthy controls. As related to total salivary protein levels, higher MCP-1 (P = 0.003) and fractalkine (P = 0.045) concentrations were found in controls compared with the P group. In serum, MCP-1 concentrations in the RA+P group were higher (P = 0.003) than those of group P. Elevated serum fractalkine concentrations were observed in both periodontitis groups (RA+P, P = 0.014; and P, P = 0.013) compared with controls. CONCLUSIONS: In RA, MCP-1, MIF, and fractalkine concentrations are elevated in saliva. These chemokines may disrupt oral macrophage responses and potentially take part in the interaction between periodontitis and RA.
34713773 The role of NLRP3 inflammasome in the pathogenesis of rheumatic disease. 2022 Feb Inflammasome is a molecular platform that is formed in the cytosolic compartment to mediate host immune responses to infection and cellular damage. Inflammasome can activate caspase-1, leading to the maturation of two inflammatory cytokines interleukin 1β (IL-1β) and IL-18 and initiation of a proinflammatory form of cell death called pyroptosis. Among various inflammasome complexes, the NLRP3 inflammasome is by far the most studied inflammasome. NLRP3 inflammasome is a key factor in regulating host immune defense against infectious microbes and cellular damage. However, the dysregulated NLRP3 inflammasome activation also participates in the pathogenesis of many human disorders. NLRP3 inflammasome plays an important role in the pathogenesis of rheumatic disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), Sjögren's syndrome (SS), dermatomyositis/polymyositis (DM/PM), gout, and systemic sclerosis (SSc). For example, NLRP3 inflammasome has been found highly activated in synovial tissues and peripheral blood mononuclear cells from RA patients. In this paper, we will discuss the role of NLRP3 inflammasome in the pathogenesis of rheumatic disease.
32725883 Predictors of long-term clinical remission in rheumatoid arthritis. 2021 Feb AIM: Little is known about possible predictors of long-term survival on biologic disease-modifying antirheumatic drugs (bDMARD) after achievement of deep clinical remission in rheumatoid arthritis (RA) patients. We aimed at assessing factors associated with drug persistence of the first bDMARD in RA patients who achieved Simplified Disease Activity Index (SDAI) remission. METHODS: The clinical charts of RA patients beginning a first bDMARD were retrospectively reviewed, and those who achieved SDAI-based remission were selected for this analysis. Drug retention rate and mean survival time (MST) were estimated using Kaplan-Meier curves, and hazard ratios (HRs) of discontinuing bDMARD were estimated by multivariate Cox-regression models. RESULTS: Eight-six patients were on SDAI remission, and the survival rate of bDMARDs since 'baseline-time' was 82.6% (MST = 77.8 (95% CI: 69-86) months). Once on remission, patients not taking concomitant glucocorticoids had significantly higher survival rate (90.7%, MST = 86.3 (95% CI: 78-95) months) than patients who continued to intake low dose of glucocorticoids (68.8%, MST = 56.9 (95% CI: 45-69) months; P = .008). On the contrary, those patients assuming methotrexate (MTX) had significantly higher survival (87.7% (MST = 81.8 (95% CI: 73-91) months) than patients who were not taking MTX (66.7% (MST = 55.3 (95% CI: 40-71) months) (log-rank 4.72, P = .03). After the achievement of disease remission, stopping glucocorticoids (HR 0.31, 95% CI: 0.10-0.93) and methotrexate co-therapy (HR 0.34, 95% CI: 0.12-0.98) were independently associated with a lower risk of bDMARD discontinuation. CONCLUSIONS: Among RA patients on clinical remission with a first bDMARD, those stopping glucocorticoids and continuing MTX had much longer survival on bDMARD.