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ID PMID Title PublicationDate abstract
32322117 The clinical phenotype associated with antisynthetase autoantibodies. 2020 OBJECTIVES: Specific systemic autoimmune syndrome characterized by inflammatory myopathy, arthritis or arthralgias, interstitial lung disease (ILD), fever, Raynaud's phenomenon, and mechanic's hands is called antisynthetase syndrome (AS). The aim of this study was to assess the clinical spectrum associated with presence of aminoacyl-transfer RNA synthetase autoantibodies (ASA). MATERIAL AND METHODS: A total of 305 patients with presence of myositis-specific autoantibodies were identified in the database of immunological tests performed in the Clinical Immunology and Transplantology Unit, Medical University of Gdansk between January 2011 and March 2016. In 110 patients (36%) ASA were detected. The detailed analysis included 50 patients with ASA for whom full clinical data were available. RESULTS: The incidence of specific ASA in the analyzed group was: Jo-1 46% (23 patients), PL-12 32% (16 patients), PL-7 16% (8 patients), OJ 12% (6 patients), EJ 6% (3 patients). In 10% (5 patients) there was coexistence of at least one ASA, and in another 5 patients there was coexistence of ASA with other antibodies specific for myositis (MSA). In the analyzed group of patients 11 (22%) satisfied the Bohan and Peter criteria for dermatomyositis, 1 for polymyositis. In 5 patients (10%) based on clinical presentation and ASA presence the AS was recognized. Another 3 patients met the criteria of the overlap syndrome polymyositis respectively with systemic lupus, rheumatoid arthritis, and scleroderma. In 5 patients undifferentiated connective tissue disease was diagnosed, and 14 consecutive patients were diagnosed with other connective tissue diseases, while 12 patients did not receive a definitive diagnosis. CONCLUSIONS: The clinical presentation of patients with the presence of ASA is varied. Their presence indicates not only idiopathic inflammatory myopathies, but also non-specifically other disease entities. These patients require observation for the development of idiopathic inflammatory myopathy, and ILD.
33370961 Infliximab-induced optic neuritis. 2020 Dec 22 Antitumour necrosis factor alpha agents are important treatments in many inflammatory conditions including rheumatoid arthritis, psoriatic arthritis and the inflammatory bowel diseases. However, there have been case reports of optic neuritis and other demyelinating diseases as complications of these agents. This case report presents a patient with ulcerative colitis on infliximab who presented with sudden onset mono-ocular visual field loss and highlights the diagnosis and management of infliximab-induced optic neuritis.
33094664 LncRNAs in adaptive immunity: role in physiological and pathological conditions. 2021 May The adaptive immune system is responsible for generating immunological response and immunological memory. Regulation of adaptive immunity including B cell and T cell biology was mainly understood from the protein and microRNA perspective. However, long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs (ncRNAs) that influence key factors in lymphocyte biology such as NOTCH, PAX5, MYC and EZH2. LncRNAs were described to modulate lymphocyte activation by regulating pathways such as NFAT, NFκB, MYC, interferon and TCR/BCR signalling (NRON, NKILA, BCALM, GAS5, PVT1), and cell effector functions (IFNG-AS1, TH2-LCR). Here we review lncRNA involvement in adaptive immunity and the implications for autoimmune diseases (multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis) and T/B cell leukaemias and lymphomas (CLL, MCL, DLBCL, T-ALL). It is becoming clear that lncRNAs are important in adaptive immune response and provide new insights into its orchestration.
32729069 Autoimmunity in 2019. 2020 Dec Based on the PubMed data, we have been performing a yearly evaluation of the publications related to autoimmune diseases and immunology to ascertain the relative weight of the former in the scientific literature. It is particularly intriguing to observe that despite the numerous new avenues of immune-related mechanisms, such as cancer immunotherapy, the proportion of immunology manuscripts related to autoimmunity continues to increase and has been approaching 20% in 2019. As in the previous 13 years, we performed an arbitrary selection of the peer-reviewed articles published by the major dedicated Journals and discussed the common themes which continue to outnumber peculiarites in autoimmune diseases. The investigated areas included systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), autoantibodies (autoAbs), and common therapeutic avenues and novel pathogenic mechanisms for autoimmune conditions. Some examples include new pathogenetic evidence which is well represented by IL21 or P2X7 receptor (P2X7R) in SLE or the application of single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq), and flow cytometry for the analysis of different cellular populations in RA. Cumulatively and of interest to the clinicians, a large number of findings continue to underline the importance of a strict relationship between basic and clinical science to define new pathogenetic and therapeutic developments. The therapeutic pipeline in autoimmunity continues to grow and maintain a constant flow of new molecules, as well illustrated in RA and PsA, and this is most certainly derived from the new basic evidence and the high-throughput tools applied to autoimmune diseases.
32554720 Article placement order in rheumatology journals: a content analysis. 2020 Jun 17 OBJECTIVES: To analyse variables associated with article placement order in serial rheumatology journals. DESIGN: Content analysis. SETTING: Original articles published in seven rheumatology journals from 2013 to 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The following data were extracted from 6787 articles: order number of article in issue, gender of first and last author, geographical region, industry funding, research design and disease category. Cumulative density function plots were used to determine whether article placement distribution was different from the expected distribution. ORs for articles published in the first three places of an issue compared with the last three places were calculated. Altmetric Score and downloads were meta-analysed. RESULTS: Article placement order did not associate with author gender or geographical region but was associated with funding source and research design. In addition, articles about rheumatoid arthritis were more likely to be ordered at the front of issues (p<0.001). Articles about crystal arthritis, systemic lupus erythematosus, vasculitis, pain syndromes and paediatric rheumatic diseases were more likely to be ordered at the end of issues (all p<0.001). Association of article placement order with disease category was observed only in journals with tables of contents grouped by disease. Articles ordered in the first three places had higher Altmetric and download rates, than articles in the last three places. CONCLUSIONS: Author gender and geographical region do not influence article placement order in serial rheumatology journals. However, bias for certain disease categories is reflected in article placement order. Editorial decisions about article placement order can influence the prominence of diseases.
32632847 Autoantibody Production in Obesity: Is There Evidence for a Link Between Obesity and Autoi 2020 Sep PURPOSE OF REVIEW: During the last decades, obesity and autoimmune disorders have shown a parallel significant rise in industrialized countries. This review aims at providing a comprehensive update of the relationship between the adipose tissue in obesity and autoimmune disorders, highlighting the underlying mechanisms with a particular emphasis on adipokines and pro-inflammatory cytokines, the impaired B cell activity, and the production of natural and pathogenic autoantibody repertoire in the context of obesity. RECENT FINDINGS: Obesity is related to a higher risk of rheumatoid arthritis, psoriasis and psoriatic arthritis, multiple sclerosis, and Hashimoto's thyroiditis, while it may promote inflammatory bowel disorders and type 1 diabetes mellitus. Interestingly, subjects with obesity present more severe forms of these autoimmune disorders as well as decreased therapeutic response. Both obesity and autoimmune disorders present elevated levels of leptin, resistin, and visfatin. Autoantibody production, a hallmark of autoimmune disorders, has been demonstrated in obese animal models and human subjects. Obesity results in deficiencies of the human self-tolerance mechanisms by promoting pro-inflammatory processes, reducing Bregs as well as Tregs, and the latter resulting in increased Th17 and Th1 cells, creating the perfect milieu for the development of autoimmune disorders. More mechanistic, animal, and clinical studies are required to delineate the exact mechanisms underlying auto-reactivity in obesity as well as the adipose-immune crosstalk for potential successful therapeutic strategies.
32057541 Endoplasmic reticulum-associated degradation and beyond: The multitasking roles for HRD1 i 2020 May Endoplasmic reticulum (ER)-associated degradation (ERAD) is a mechanism against ER stress, wherein unfolded/misfolded proteins accumulated in the ER are transported to the cytosol for degradation by the ubiquitin-proteasome system. The ER resident E3 ubiquitin ligase HRD1 has been identified as a key ERAD factor that directly catalyzes ubiquitin conjugation onto the unfolded or misfolded proteins for proteasomal degradation. The abnormally increased HRD1 expression was discovered in rheumatoid synovial cells, providing the first evidence for HRD1 dysregulation involved in human inflammatory pathogenesis. Further studies shown that inflammatory cytokines involved in rheumatoid pathogenesis including IL-1β, TNF-α, IL-17 and IL-26 induce HRD1 expression. Recent studies using mice with tissue-specific targeted deletion of HRD1 gene have revealed important functions of HRD1 in immune regulation and inflammatory diseases. HRD1 has been shown critical for dendritic cell expression of antigens to both CD4 and CD8 T cells. Both TCR and costimulatory receptor CD28 signaling induces HRD1 expression, which promotes T cell clonal expansion and IL-2 production. Together with the fact that HRD1 is required for maintaining the stability of regulatory T cell (Treg) stability, HRD1 appears to fine tone T cell immunity. In addition, HRD1 is involved in humoral immune response by regulating early B cell development and maintaining B cell survival upon recognition of specific antigen. HRD1 appears to target its substrates for ubiquitination through, either ERAD-dependent or -independent, at least two distinct molecular mechanisms in a cell or tissue specific manner to achieve its physiological functions. Dysregulation of HRD1 expression and/or it functions are involved in autoimmune inflammatory diseases in particular rheumatoid arthritis and lupus. Here, we review current findings on the mechanism of HRD1 protein in immune regulation and the involvement of HRD1 in the pathogenesis of autoimmune inflammatory diseases.
31943973 Responses to Cytokine Inhibitors Associated with Cellular Composition in Models of Immune- 2020 Jan OBJECTIVE: Immune-mediated inflammatory arthritis (IMIA) is a heterogeneous group of diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA). Disease-modifying antirheumatic drugs (DMARDs) target very different cellular components of the disease processes. Characterization of the pathobiological subtypes of IMIA could provide more specific treatment approaches for each disease. For example, RA has been proposed to consist of at least three synovial pathotypes (lymphoid, myeloid, and fibroid), and only a subgroup of RA patients have erosive disease. The objective of this study was to evaluate the effects of various DMARDs on different synovial cell subsets using human ex vivo models of IMIA. METHODS: Synovial fluid and blood samples were obtained from a study population consisting of patients with RA, PsA, or peripheral SpA with at least one swollen joint (n = 18). The DMARDs used in this study were methotrexate, adalimumab, etanercept, tocilizumab, anakinra, ustekinumab, secukinumab, tofacitinib, and baricitinib. Paired synovial fluid mononuclear cells (SFMCs), peripheral blood mononuclear cells (PBMCs), and fibroblast-like synovial cells (FLSs) were used in three different previously optimized ex vivo models. RESULTS: In SFMCs cultured for 48 hours, all DMARDs except anakinra decreased the production of monocyte chemoattractant protein (MCP)-1. In SFMCs cultured for 21 days, only the two tumor necrosis factor alpha (TNFα) inhibitors adalimumab and etanercept decreased the secretion of tartrate-resistant acid phosphatase (P < 0.01, P < 0.001). In the FLS and PBMC 48-hour co-cultures, only tocilizumab (P < 0.001) and the two Janus kinase inhibitors tofacitinib and baricitinib (both P < 0.05) decreased the production of MCP-1 by around 50%. CONCLUSION: TNFα inhibition was effective in preventing inflammatory osteoclastogenesis, whereas tocilizumab, tofacitinib, and baricitinib had superior efficacy in cultures dominated by FLSs. Taken together, this study reveals that responses to cytokine inhibitors associate with cellular composition in models of IMIA. In particular, this study provides new evidence on the differential effect of DMARDs on leukocytes compared with stromal cells.
32522458 Multimodal VEGF-Targeted Contrast-Enhanced Ultrasound and Photoacoustic Imaging of Rats wi 2020 Sep Owing to the heavy health burdens from rheumatoid arthritis, a sensitive and objective imaging method is needed for early diagnosis and accurate evaluation of the disease. We aimed to fabricate vascular epithelial growth factor (VEGF)-targeted microbubbles (MBs) to evaluate the expression levels of VEGF within the inflammatory lesions of rats with adjuvant-induced arthritis (AIA) using a multimodal photoacoustic (PA)/ultrasound (US) imaging system. Fluorescein isothiocyanate-biotin double-labeled vascular endothelial growth factor receptor 2 antibodies and Cy5.5-biotin double-labeled VEGF2 antibodies were added to the avidin-labeled MBs to synthesize VEGF-targeted MBs. The antibodies could specifically bind to the MBs according to the flow cytometry and fluorescence imaging. In vitro experiments on the cellular uptake of the target MBs also validated the interaction of the VEGF antibodies and the MBs. Multimodal contrast-enhanced US (CEUS)/PA imaging was performed in sequence on the inflamed paws of the AIA rats with a single PA/US imaging system after the injection of the targeted MBs. The CEUS and PA signals were then quantified and verified by the pathologic results. A CEUS pattern of fast wash in and slow washout was observed in the AIA rats after injection of targeted MBs. Compared with AIA rats injected with unconnected VEGF antibodies and naked MBs, AIA rats injected with targeted MBs presented a higher peak intensity (p = 0.0079 and 0.0079 respectively) and a longer time to peak (p = 0.0117 and 0.0117, respectively). The PA signals were also significantly enhanced after injection of targeted MBs (p = 0.0112 and 0.0119, respectively), which was in accordance with the pathologic and immunohistochemical results. In conclusion, VEGF-targeted MBs can be used as agents for multimodal CEUS/PA imaging and to detect VEGF expression in the inflammatory lesions of AIA rats in vivo. This strategy may be useful in imaging evaluation of arthritis by identifying inflammation-related molecules in different imaging modes.
32466852 Alteration of CD226/TIGIT immune checkpoint on T cells in the pathogenesis of primary Sjö 2020 Sep OBJECTIVES: Hyperactivity of T lymphocytes might play an important role in the pathogenesis of primary Sjögren's syndrome (pSS). CD226/T cell immunoglobulin and ITIM domain (TIGIT) pathway is a newly identified immune checkpoint involved in the pathogenesis of cancer and rheumatic diseases. However, its role in the pathophysiology of pSS is obscure. Hence, this study aimed to explore the potential role of CD226/TIGIT expression on T cells in the pathogenesis of pSS. METHODS: In patients with pSS, other rheumatic disease controls (DCs), and healthy controls (HCs), the expression of CD226 and TIGIT on T cells along with their activity following stimulation were detected by flow cytometry. The correlations between the expression of CD226 and TIGIT on T cells and clinical data were analyzed. RESULTS: The frequencies of CD226/TIGIT expressing CD4(+) and CD8(+) T cells were significantly higher in patients with pSS than in HCs and DCs. Among them, the TIGIT/CD226 expressing CD4(+) T cells closely correlated with pSS disease activity: the percentages of CD4(+)CD226(+) and CD4(+)TIGIT(+) T cells were significantly higher in the active pSS than the inactive pSS. The proportion of CD4(+)TIGIT(+) T cells positively correlated with the erythrocyte sedimentation rate. Further in vitro analysis revealed that CD4(+)CD226(+) T cells exerted superior effector function than the CD226(-) counterparts in both pSS and HCs. TIGIT was preferably expressed on activated cells, and the activity of CD4(+)TIGIT(+) T cells was comparable with CD4(+)TIGIT(-) T cells in HCs. However, in pSS, CD4(+)TIGIT(+) T cells showed enhanced activity than the CD4(+) TIGIT(-) T cells. CONCLUSION: CD226/TIGIT checkpoint molecules were over-expressed on T cells in pSS. Proportional and functional alteration of CD226/TIGIT expressing CD4(+) T cells may be involved in the pathogenesis of pSS, and be a potential novel therapeutic target for the disease.
32358369 Clinical significance of progranulin correlated with serum soluble Oxford 40 ligand in pri 2020 May The present study aimed to investigate the association between the expressions of serum progranulin (PGRN) and serum soluble Oxford 40 ligand (sOX40L) and determine their clinical significances in primary Sjögren's syndrome (pSS).The present study included a total of 68 patients with pSS and 50 healthy controls. Demographic data and clinical basic information were collected. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum levels of PGRN, sOX40L and interleukins. Spearman's correlation coefficient and Mann-Whitney U test were used to determine the correlation between PGRN, and sOX40L and the association between PGRN and sOX40L and disease activity and disease severity.Serum interleukin (IL)-4, IL-6, IL-10, PGRN, and sOX40L levels were significantly higher in pSS patients as compared to the healthy controls. A positive correlation was observed between PGRN and sOX40L. Patients with elevated levels of PGRN or sOX40L exhibited higher disease activity compared to those with lower levels. Patients with III to IV stages of pSS or multiple system damage showed higher serum levels of PGRN and sOX40L.Elevated serum PGRN, and sOX40L levels were relevant with disease activity and severity in patients with pSS.
33179091 Mesenchymal stem cells negatively regulate CD4+ T cell activation in patients w 2021 Jan Treatment with mesenchymal stem cells (MSCs) has been revealed to suppress CD4+ T cells and autoimmunity in both mouse models and patients with primary Sjögren syndrome (pSS); however, the underlying mechanism remains unclear. MicroRNAs (miRNAs or miRs) mediate CD4+ T cell activation, but the mechanism is not understood, particularly for CD4+ T cells treated with MSCs. Characterization of miRNAs may reveal pSS pathogenesis, guide MSC treatment and provide more personalized management options. The present study aimed to perform an miRNome analysis of quiescent and T cell receptor (TCR)‑activated CD4+ T cells treated with MSCs via miRNA profiles and bioinformatics. Following 72 h of co‑culture, MSCs inhibited TCR‑induced CD4+ T cell activation and decreased IFN‑γ levels. The numbers of aberrant miRNAs in pSS naïve (vs. healthy naïve), pSS activation (vs. pSS naïve), MSC treatment and pre‑IFN‑γ MSC treatment (vs. pSS activation) groups were 42, 55, 27 and 32, respectively. Gene enrichment analysis revealed that 259 pathways were associated with CD4+ T cell stimulation, and 240 pathways were associated with MSC treatment. Increased miRNA‑7150 and miRNA‑5096 and decreased miRNA‑125b‑5p and miRNA‑22‑3p levels in activated CD4+ T cells from patients with pSS were reversed by MSC treatment. Notably, the proliferation of CD4+ T cells and CD4+ IFN‑γ+ cells, expression levels of miRNA‑125b‑5p and miRNA‑155 in CD4+ T cells and supernatant IFN‑γ secretion were associated with disease activity. miRNA may play a vital role in MSC treatment for activated CD4+ T cells. The results indicated that the expression levels of miRNA‑125b‑5p and miRNA‑155 in TCR‑activated CD4+ T cells from patients with pSS may provide insight regarding autoimmune diseases and offer a novel target for prospective treatment. Therefore, these results may be crucial in providing MSC treatment for pSS.
32153241 Population-based study of patients with primary Sjögren's syndrome and lymphoma: lymphoma 2020 May Objective: To examine lymphoma subtypes, clinical characteristics, and gender differences in patients with primary Sjögren's syndrome (pSS) and lymphoma in a population-based setting.Method: Patients with Sjögren's syndrome and lymphoma diagnoses were identified by linkage of the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007. Clinical data were collected from medical records and lymphoma tissues were re-examined. The lymphoma subtype distribution was compared with the Swedish Lymphoma Register.Results: We identified 105 pSS patients with lymphoma. Diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma [MZL including mucosa-associated lymphoid tissue (MALT) lymphoma] (31%) were the most common lymphoma subtypes. The proportion of DLBCL was not increased compared to the general population reference (32%, p = 1), in contrast to MZL (general population 5%, p < 0.0001). Compared to DLBCL, MALT lymphoma was diagnosed at a younger age (55 vs 67 years, p = 0.0001), and earlier after patient-reported sicca onset (7 vs 18 years, p = 0.0001) and pSS diagnosis (2 vs 9 years, p = 0.0005). Sixteen of the pSS-lymphoma cases were men (15%), twice the proportion in general pSS populations. Compared to women, men had a shorter median time from pSS diagnosis to lymphoma diagnosis (1 vs 8 years, p = 0.0003) and more often had lymphoma in the salivary glands (56% vs 29%, p = 0.04).Conclusion: DLBCL and MZL are common in pSS patients, but only MZL/MALT lymphoma occurs at an increased relative frequency in pSS compared to the general population. The study supports increased awareness of signs of lymphoma in men in the first years after pSS diagnosis.
31490711 Transgenic rice seeds expressing altered peptide ligands against the M3 muscarinic acetylc 2020 Sep Objective: We previously reported that Rag1(-/-) mice inoculated with splenocytes from M3 muscarinic acetylcholine receptor (M3R) knockout mice immunized with an M3R peptide mixture developed sialadenitis-like Sjögren's syndrome (M3R-induced sialadenitis [MIS]). We also found that intravenous administration of altered peptide ligand (APL) of N-terminal 1 (N1), which is one of the T-cell epitopes of M3R, suppressed MIS. In this study, we aimed to evaluate the suppressive ability and its mechanisms of rice seeds expressing N1-APL7 against MIS.Methods: Rice seeds expressing N1 and N1-APL7 were orally administered to MIS mice for 2 weeks. The changes in saliva flow and sialadenitis (salivary gland inflammation) were analyzed. The M3R-specific T-cell response in the spleen and the expression of regulatory molecules in the cervical lymph nodes and mesenteric lymph nodes were also analyzed.Results: Oral administration of N1-APL7-expressing rice seeds significantly recovered reduction in saliva flow and suppressed sialadenitis when compared with treatment with nontransgenic rice seeds and N1 rice seeds. IFNγ production from M3R-reactive T cells tended to decline in the N1-APL7 rice-treated group as compared with those in the other groups. In the N1-APL7 rice-treated group, the mRNA expression levels of Foxp3 in the cervical-lymph-node CD4(+) T cells were higher than those in the other groups.Conclusion: Oral administration of N1-APL7-expressing rice suppressed MIS via suppression of M3R-specific IFNγ and IL-17 production and via enhancement of regulatory molecule expression.Key messagesWe generated N1-peptide- or N1-APL7-expressing rice seeds. Oral administration of N1-APL7-expressing rice seeds significantly recovered the reduction of saliva flow and suppressed sialadenitis via the suppression of M3R specific IFNγ and IL-17 production and via enhancement of regulatory T (Treg) cells.
32510591 Δ(9) -Tetrahydrocannabinolic acid alleviates collagen-induced arthritis: Role of PPARγ a 2020 Sep BACKGROUND AND PURPOSE: Δ(9) -Tetrahydrocannabinolic acid (Δ(9) -THCA-A), the precursor of Δ(9) -THC, is a non-psychotropic phytocannabinoid that shows PPARγ agonist activity. Here, we investigated the ability of Δ(9) -THCA-A to modulate the classic cannabinoid CB(1) and CB(2) receptors and evaluated its anti-arthritis activity in vitro and in vivo. EXPERIMENTAL APPROACH: Cannabinoid receptors binding and intrinsic activity, as well as their downstream signalling, were analysed in vitro and in silico. The anti-arthritis properties of Δ(9) -THCA-A were studied in human chondrocytes and in the murine model of collagen-induced arthritis (CIA). Plasma disease biomarkers were identified by LC-MS/MS based on proteomic and elisa assays. KEY RESULTS: Functional and docking analyses showed that Δ(9) -THCA-A can act as an orthosteric CB(1) receptor agonist and also as a positive allosteric modulator in the presence of CP-55,940. Also, Δ(9) -THCA-A seemed to be an inverse agonist for CB(2) receptors. In vivo, Δ(9) -THCA-A reduced arthritis in CIA mice, preventing the infiltration of inflammatory cells, synovium hyperplasia, and cartilage damage. Furthermore, Δ(9) -THCA-A inhibited expression of inflammatory and catabolic genes on knee joints. The anti-arthritic effect of Δ(9) -THCA-A was blocked by either SR141716 or T0070907. Analysis of plasma biomarkers, and determination of cytokines and anti-collagen antibodies confirmed that Δ(9) -THCA-A mediated its activity mainly through PPARγ and CB(1) receptor pathways. CONCLUSION AND IMPLICATIONS: Δ(9) -THCA-A modulates CB(1) receptors through the orthosteric and allosteric binding sites. In addition, Δ(9) -THCA-A exerts anti-arthritis activity through CB(1) receptors and PPARγ pathways, highlighting its potential for the treatment of chronic inflammatory diseases such as rheumatoid arthritis.
32080619 Tendon and ligament mechanical loading in the pathogenesis of inflammatory arthritis. 2020 Apr Mechanical loading is an important factor in musculoskeletal health and disease. Tendons and ligaments require physiological levels of mechanical loading to develop and maintain their tissue architecture, a process that is achieved at the cellular level through mechanotransduction-mediated fine tuning of the extracellular matrix by tendon and ligament stromal cells. Pathological levels of force represent a biological (mechanical) stress that elicits an immune system-mediated tissue repair pathway in tendons and ligaments. The biomechanics and mechanobiology of tendons and ligaments form the basis for understanding how such tissues sense and respond to mechanical force, and the anatomical extent of several mechanical stress-related disorders in tendons and ligaments overlaps with that of chronic inflammatory arthritis in joints. The role of mechanical stress in 'overuse' injuries, such as tendinopathy, has long been known, but mechanical stress is now also emerging as a possible trigger for some forms of chronic inflammatory arthritis, including spondyloarthritis and rheumatoid arthritis. Thus, seemingly diverse diseases of the musculoskeletal system might have similar mechanisms of immunopathogenesis owing to conserved responses to mechanical stress.
33200729 Autoantibody profile in eosinophilic granulomatosis and polyangiitis: predominance of anti 2021 Mar OBJECTIVES: To evaluate the autoantibody profile in eosinophilic granulomatosis and polyangiitis (EGPA) patients. METHODS: 33 EGPA patients were tested for anti-neutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), rheumatoid factor (RF), anti-alpha-enolase antibodies, and anti-eosinophil peroxidase (EPO) antibodies. Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), hypereosinophilic syndrome (HES), rheumatoid arthritis (RA), primary biliary cirrhosis (PBC) patients and healthy subjects were tested as a control group. RESULTS: Anti-alpha-enolase antibodies were positive in 82% of EGPA patients at high titers. Although a high sensitivity was shown for an anti-alpha-enolase antibody titer above 1/100 (82%), the specificity for EGPA remained low (44%) (AUC=0.653, p=0.008). Anti-alpha-enolase antibodies predominated in males with EGPA (p=0.048) and were associated with skin involvement (p=0.040). Most of the EGPA patients positive for anti-alpha enolase antibodies (20 out of 27) had a negative indirect immunofluorescence test (IFT) for ANCA. ANCA were positive in 8 EGPA patients (24%) with a perinuclear pattern in all but one patient. The ANCA-target antigen was myeloperoxidase (MPO) and/or alpha-enolase. A usually fine-speckled ANA pattern was observed in 42% of the EGPA patients. RF was positive in 1 (6%) of the 18 EGPA patients tested. There was no association between the presence and levels of autoantibodies and EGPA disease activity. None of the patients and controls was positive for anti-EPO antibodies. CONCLUSIONS: Alpha-enolase may be a target of autoimmunity in EGPA patients and shows usually negative ANCA IFT results.
33072123 Role of Extracellular Vesicles in Autoimmune Pathogenesis. 2020 Autoimmune diseases are conditions that emerge from abnormal immune responses to natural parts of the body. Extracellular vesicles (EVs) are membranous structures found in almost all types of cells. Because EVs often transport "cargo" between cells, their ability to crosstalk may be an important communication pathway within the body. The pathophysiological role of EVs is increasingly recognized in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Type 1 diabetes, and autoimmune thyroid disease. EVs are considered as biomarkers of these diseases. This article outlines existing knowledge on the biogenesis of EVs, their role as messegers in cellular communication and the function in T/B cell differentiation and maturation, and focusing on their potential application in autoimmune diseases.
32645531 Rheological properties of synovial fluid due to viscosupplements: A review for osteoarthri 2020 Nov The synovial fluid is a transparent electrolyte solution included in joints to provide lubrication helping the proper movement. It exhibits complex rheological properties due to the interaction among its constituents i.e. hyaluronic acid, albumin, lubricin and phospholipids. In degenerative osteoarthritis and inflammatory rheumatoid arthritis diseases, the quantity of synovial fluid and lubrication efficiency significantly deteriorates. In that case, viscosupplementation with intra-articular hyaluronic acid may be prescribed to replenish the concentration, the molecular weight and the rheological properties of natural synovial fluid. The present review concentrates on the recent advancements in viscosupplementation with emphasis into their rheological properties, its effects on the rheological behavior of synovial fluid, and finally its clinical effectiveness. Initially, the properties of synovial fluid are summarized, and then a discussion on commercial viscosupplements, the role of polymeric properties and their rheological properties are reviewed. Moreover, a detailed discussion on the clinical effectiveness and challenges of viscosupplements are provided.
31884014 Evaluation of an Immediate-Release Formulation of Hydroxychloroquine Sulfate With an Inter 2020 Apr Hydroxychloroquine sulfate (HCQ) is a quinoline used for the prevention and treatment of uncomplicated malaria, lupus erythematosus, and rheumatoid arthritis. For each indication, HCQ is an option for treatment of pediatric and juvenile patients on a weight basis; however, no tailored pediatric product is available on the market. Preliminary research confirmed that a slightly buffered, ion-pairing system significantly reduces the bitterness of HCQ, suggesting a high likelihood that a pediatric taste-masking system could be interwoven into an adult immediate-release formulation allowing the creation of a palatable suspension with water using common excipients. Because HCQ is a Biopharmaceutics Classification System Class 1 drug, the pharmacokinetics for an adult immediate-release formulation would not be altered by embeding a taste-masking system. Embedding the taste-masking and suspension agents within the adult tablet formulation would remove the need for aqueous-based vehicles and simplify the creation of a water-based suspension formulation to support improved compliance, dosing accuracy, and health outcomes in pediatric patients who are weight-base dosed with HCQ.