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ID PMID Title PublicationDate abstract
32094142 Using internet search data to explore the global public concerns in ankylosing spondylitis 2021 Feb OBJECTIVE: This study explored the changes of global public interest in internet search of ankylosing spondylitis (AS) based on Google Trends (GT) data, in order to reflect the characteristics of AS itself. METHODS: GT was used to obtain the search popularity scores of the term 'AS' on a global scale, between January 2004 and December 2018, under the 'health' classification. Based on the global search data of AS provided by GT, the cosinor analysis was used to test whether there was seasonality in AS. RESULTS: In general, AS related search volume demonstrated a decreasing trend from January 2004 to December 2014 and then remain stable from January 2015 to December 2018. No obvious seasonal variations were detected in AS related search volume (amplitude=1.54; phase: month=3.9; low point: month=9.9; p>0.025), which peaked in April and bottomed out in October. The top 17 rising topics were adalimumab, spondylolisthesis, Morbus, Vladimir Mikhailovich Bekhterev, autoimmune disease, rheumatoid arthritis, ankylosis, HLA- B27 positive, Crohn's disease, rheumatology, spondylosis, arthritis, uveitis, rheumatism, sacroiliac, psoriatic arthritis and spondylitis. CONCLUSIONS: Globally, there is no significant seasonal variation in GT for AS. The top fast-growing topics related to AS may be beneficial for doctors to provide targeted health education of the disease to patients and their families.
34426107 Micro RNAs 26b, 20a inversely correlate with GSK-3 β/NF-κB/NLRP-3 pathway to highlight t 2021 Oct Rheumatoid arthritis (RA) is an inflammatory disease with challenging therapeutic potential due to the implication of cross-talking intracellular pathways in the pathogenesis of the disease. This study aimed to evaluate the effects of the combination therapy of atorvastatin and quercetin on glycogen synthase kinase-3 beta/ nuclear factor kappa-B/ nucleotide-binding oligomerization domain-like receptor family pyrin domain containing-3 or inflammasome (GSK-3β/NF-KB/NLRP-3) pathway as well as on microRNAs 26b and 20a (miR-26b, miR-20a) and to investigate the possible beneficial outcomes of the combination to offer a better treatment option than methotrexate (MTX) in adjuvant-induced arthritis (AIA). Assessment of arthritis progression, serum inflammatory, and oxidative parameters were done. The tibiotarsal tissue expression of the inflammatory parameters was evaluated. Western blot analysis was done to assess the expression level of the important members in the GSK-3β/NF-κB/NLRP-3 pathway. Furthermore, the expression level of both microRNAs and serum level of transaminases were determined. All treatments, especially the combination regimen, abated arthritis progression, the elevated serum level of inflammatory and oxidative stress parameters in arthritic rats. Moreover, They down-regulated the gene expression of the important members of the aforementioned signaling pathway, amended the tissue levels of inflammatory parameters and elevated the expression level of miR-26b and miR-20a. Finally, we concluded that the combination therapy modulated miR-26b and miR-20a as well as GSK-3β/NF-κB/NLRP-3 pathway, provided additive anti-inflammatory and anti-oxidant effects and offered an additional hepatoprotective effect as compared to untreated arthritic rats and MTX-treated groups, suggesting its promising role to be used as replacement therapy to MTX in RA.
34593938 Associations of vascular and bone status in arthritis patients. 2021 Sep 30 Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p < 0.05). Moreover, total and trabecular BMD determined by QCT inversely correlated with IMT (p < 0.05). On the other hand, among vascular parameters, platelet-derived growth factor BB and IMT correlated with DXA femoral and QCT total BMD, respectively (p < 0.05). In the RM-ANOVA analysis, anti-TNF treatment together with baseline osteocalcin, procollagen 1 N-terminal propeptide (P1NP) or vitamin D3 levels determined one-year changes in IMT (p < 0.05). In the MANOVA analysis, baseline disease activity indices (DAS28, BASDAI), the one-year changes in these indices, as well as CRP exerted effects on multiple correlations between bone and vascular markers (p < 0.05). As the pattern of interactions between bone and vascular biomarkers differed between baseline and after 12 months, anti-TNF therapy influenced these associations. We found a great number of correlations in our RA and AS patients undergoing anti-TNF therapy. Some of the bone markers have been associated with vascular pathophysiology, while some vascular markers correlated with bone status. In arthritis, systemic inflammation and disease activity may drive both vascular and bone disease.
33547770 Intervention of Tyrosine Hydroxylase Expression Alters Joint Inflammation and Th17/Treg Im 2021 Feb 6 BACKGROUND/AIMS: Neuroendocrine dysregulation has been associated with rheumatoid arthritis (RA). Tyrosine hydroxylase (TH), a rate-limiting enzyme for synthesis of neuroendocrine hormones such as epinephrine, is also expressed in T lymphocytes and regulates balance between helper T (Th) 17 cells and regulatory T (Treg) cells. Herein, we aimed to show that TH expression in joints alleviates joint inflammation and Th17/Treg imbalance in collagen-induced arthritis (CIA), an animal model of RA, and these effects may be implemented by the mechanism of epinephrine action on α1-adrenoreceptor (α1-AR) in T cells. METHODS: CIA was prepared by intradermal injection of collagen type II in tail base of DBA1/J mice. On the 33rd day post-immunization, lentiviral vectors encoding TH or TH shRNA were injected into ankle joints of CIA mice. Limb inflammation of the mice was assessed beginning from day 21 until day 69 post-immunization by measurement of limb swelling, erythema and rigidity. Th17 and Treg differentiation and function in ankle joints were assessed on day 69 post-immunization by test of the expression of Th17 transcriptional factor ROR-γt and the levels of proinflammatory cytokines interleukin (IL)-17 and IL-22 as well as the expression of Treg transcriptional factor Foxp3 and the levels of antiinflammatory cytokines transforming growth factor (TGF)-β1 and IL-10. T cells were obtained from the spleen of mice that had been immunized with collagen type II 41 day earlier and treated with epinephrine or α1-AR agonist phenylephrine in vitro. Flow cytometry was used to analyze the percentages of CD25(-)IL-17(+) cells and CD25(+)Foxp3(+) cells in CD4(+) T cells. RESULTS: TH gene overexpression in ankle joints of CIA mice reduced limb inflammation and Th17-related transcription factor expression and inflammatory cytokine production but increased Treg-related antiinflammatory cytokine production in the joints. In contrast, TH gene silence in ankle joints of CIA mice enhanced limb inflammation and Th17 cell activity but decreased Treg cell function in the joints. Epinephrine upregulated α1-AR expression in T cells derived from CIA mice. Both epinephrine and phenylephrine reduced CIA-induced Th17 transcription factor expression and inflammatory cytokine production but enhanced Treg antiinflammatory cytokine production in vitro. CONCLUSION: Upregulating TH expression in joints alleviates joint inflammation and Th17/Treg imbalance in CIA at least partially by enhancing epinephrine action on α1-AR in T cells.
31581859 Off-label studies on tofacitinib in dermatology: a review. 2021 Jun PURPOSE: Tofacitinib citrate is an oral Janus kinase 1/3 inhibitor approved for rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis. Tofacitinib is being increasingly used off-label for dermatological conditions, with varying efficacy across recent studies. A review of these studies will be a helpful resource for dermatologists considering the use of tofacitinib for conditions refractory to first-line therapies. MATERIALS AND METHODS: MEDLINE, Embase, CINAHL Plus, Cochrane Library, Scopus, Web of Science, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform were all searched for articles and trials mentioning the term 'tofacitinib', then manually reviewed to identify published data on off-label uses of tofacitinib. The article was structured according to the quality of the evidence available. RESULTS: Tofacitinib appears to show strong efficacy for numerous dermatologic conditions. Randomized controlled trial data is available for atopic dermatitis, alopecia areata, and plaque psoriasis. Case report and case series data is available for numerous other dermatologic conditions. CONCLUSION: While tofacitinib has a wide array of immunoregulatory properties, making it a possible candidate for treating many dermatologic conditions refractory to other treatments, further testing is needed to better characterize its efficacy and utility moving forward, as well as its safety and adverse effect profile.
33673583 Association between Oncostatin M Expression and Inflammatory Phenotype in Experimental Art 2021 Feb 27 Pro-inflammatory cytokines are considered to play a major role in osteoarthritis (OA), yet so far, the specific cytokines involved in the pathology of OA have not been identified. Oncostatin M (OSM) is a cytokine from the interleukin 6 (IL-6) family that has been shown to be elevated in synovial fluid of most rheumatoid arthritis (RA) patients, but only in a limited subset of OA patients. Little is known about OSM in the different joint tissues during OA and how its expression correlates with hallmarks of disease. Here, we mapped OSM expression in the joint tissues of two rat models of arthritis: an acute inflammatory model and an instability-induced osteoarthritic model. OSM expression was correlated with hallmarks of OA, namely cartilage damage, synovitis, and osteophyte formation. Reanalysis of an existing dataset on cytokine profiling of OA synovial fluid was performed to assess pattern differences between patients positive and negative for OSM. In the inflammatory model, OSM expression correlated with synovitis and osteophyte formation but not with cartilage damage. On the contrary, in the instability model of OA, an increase in synovitis, cartilage damage, and osteophyte formation was observed without changes in OSM expression. In line with these findings, synovial fluid of OA patients with detectable OSM contained higher levels of other inflammatory cytokines, namely interferon gamma (IFN-γ), IL-1α and tumor necrosis factor alpha (TNF-α), likely indicating a more inflammatory state. Taken together these data indicate OSM might play a prominent role in inflammatory phenotypes of OA.
34064456 Characterization of Extracellular Vesicle Cargo in Sjögren's Syndrome through a SWATH-MS 2021 May 4 Primary Sjögren's syndrome (pSS) is a complex heterogeneous disease characterized by a wide spectrum of glandular and extra-glandular manifestations. In this pilot study, a SWATH-MS approach was used to monitor extracellular vesicles-enriched saliva (EVs) sub-proteome in pSS patients, to compare it with whole saliva (WS) proteome, and assess differential expressed proteins between pSS and healthy control EVs samples. Comparison between EVs and WS led to the characterization of compartment-specific proteins with a moderate degree of overlap. A total of 290 proteins were identified and quantified in EVs from healthy and pSS patients. Among those, 121 proteins were found to be differentially expressed in pSS, 82% were found to be upregulated, and 18% downregulated in pSS samples. The most representative functional pathways associated to the protein networks were related to immune-innate response, including several members of S100 protein family, annexin A2, resistin, serpin peptidase inhibitors, azurocidin, and CD14 monocyte differentiation antigen. Our results highlight the usefulness of EVs for the discovery of novel salivary-omic biomarkers and open novel perspectives in pSS for the identification of proteins of clinical relevance that could be used not only for the disease diagnosis but also to improve patients' stratification and treatment-monitoring. Data are available via ProteomeXchange with identifier PXD025649.
34112769 A new molecular classification to drive precision treatment strategies in primary Sjögren 2021 Jun 10 There is currently no approved treatment for primary Sjögren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials.
33936904 An Atypical Presentation of Polyarteritis Nodosa: Case Report and Review of the Literature 2021 Mar 30 Polyarteritis nodosa (PAN) is a rare multisystem vasculopathy that predominantly affects medium-sized arteries. Involvement of the cardiac and/or pulmonary vasculature may be fatal. We describe a 67-year-old Japanese male who presented with multiple coronary artery aneurysms and subsequently developed lower extremity gangrene. A diagnosis of PAN was established based on the correlation of clinical presentation and laboratory and imaging findings. In addition, we review other manifestations of PAN and differential considerations for this rare but potentially lethal condition.
32644548 Type III Hypersensitivity Reaction. 2022 Jan A hypersensitivity reaction is an inappropriate or overreactive immune response to an antigen resulting in undesirable effects. The symptoms typically appear in an individual who had at least one previous exposure to the antigen. Hypersensitivity reactions can be classified into four types. Type I - IgE mediated immediate reaction Type II- Antibody-mediated cytotoxic reaction (IgG or IgM antibodies) Type III- Immune complex-mediated reaction Type IV- Cell-mediated, delayed hypersensitivity reaction Type III hypersensitivity reaction In type III hypersensitivity reaction, an abnormal immune response is mediated by the formation of antigen-antibody aggregates called "immune complexes." They can precipitate in various tissues such as skin, joints, vessels, or glomeruli, and trigger the classical complement pathway. Complement activation leads to the recruitment of inflammatory cells (monocytes and neutrophils) that release lysosomal enzymes and free radicals at the site of immune complexes, causing tissue damage. The most common diseases involving a type III hypersensitivity reaction are serum sickness, post-streptococcal glomerulonephritis, systemic lupus erythematosus, farmers' lung (hypersensitivity pneumonitis), and rheumatoid arthritis. The principle feature that separates type III reactions from other hypersensitivity reactions is that in type III reaction, the antigen-antibody complexes are pre-formed in the circulation before their deposition in tissues.
34346821 Late-onset Etanercept-associated Ocular Sarcoidosis with Profound Vision Loss. 2021 Aug 4 INTRODUCTION: Etanercept is a tumor necrosis factor-alpha-blocking immunosuppressive agent and carries the risk of paradoxical induction of sarcoidosis. We present a case of a 75-year-old woman with rheumatoid arthritis treated with etanercept who developed etanercept-associated ocular sarcoidosis after 4 years of therapy. CASE REPORT: The patient presented to clinic with visual acuity of light perception in the right eye and hand motions in the left eye. Examination revealed optic disc edema in both eyes with serous retinal detachment in the right eye. Work-up revealed an elevated serum angiotensin-converting enzyme level, and computed tomographic scan of the chest revealed innumerable bilateral peribronchial pulmonary nodules with calcifications. A diagnosis of presumed ocular sarcoidosis was made. Etanercept was stopped, and the patient was treated with oral prednisone and subcutaneous methotrexate, with clinical and visual recovery. CONCLUSIONS: Etanercept-associated sarcoidosis can occur at any time after initiating therapy and should be considered in patients on etanercept with ocular inflammation.
34267882 Discovery of Potent Selective Nonzinc Binding Autotaxin Inhibitor BIO-32546. 2021 Jul 8 Autotaxin (ATX) is a lysophospholipase D that is the main enzyme responsible for generating LPA in body fluids. Although ATX was isolated from a conditioned medium of melanoma cells, later it was discovered to play a critical role in vascular and neuronal development. ATX has also been implicated in primary brain tumor, fibrosis, and rheumatoid arthritis, as well as neurological diseases such as multiple sclerosis, Alzheimer's disease, and neuropathic pain. As ATX and LPA levels are increased upon neuronal injury, a selective ATX inhibitor could provide a new approach to treat neuropathic pain. Herein we describe the discovery of a novel series of nonzinc binding reversible ATX inhibitors, particularly a potent, selective, orally bioavailable, brain-penetrable tool compound BIO-32546, as well as its synthesis, X-ray cocrystal structure, pharmacokinetics, and in vivo efficacy.
33981318 Toll-Like Receptors Gene Polymorphisms in Autoimmune Disease. 2021 Toll-like receptors (TLRs) are important initiators of the immune response, both innate and acquired. Evidence suggests that gene polymorphisms within TLRs cause malfunctions of certain key TLR-related signaling pathways, which subsequently increases the risk of autoimmune diseases. We illustrate and discuss the current findings on the role of Toll-like receptor gene polymorphisms in numerous autoimmune diseases in this review, such as type 1 diabetes mellitus, Graves' disease, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. The study of genetic variation in TLRs in different populations has shown a complex interaction between immunity and environmental factors. This interaction suggests that TLR polymorphisms affect the susceptibility to autoimmune diseases differently in various populations. The identification of Toll-like receptor gene polymorphisms can expand our understanding of the pathogenesis of autoimmune diseases, which will subsequently guide effective medical management and provide insight into prognosis and advanced treatments.
33884656 Phenotypes, roles, and modulation of regulatory lymphocytes in periodontitis and its assoc 2022 Feb Periodontitis is a common chronic inflammatory disease that can result in tooth loss and poses a risk to systemic health. Lymphocytes play important roles in periodontitis through multiple mechanisms. Regulatory lymphocytes including regulatory B cells (Bregs) and T cells (Tregs) are the main immunosuppressive cells that maintain immune homeostasis, and are critical to our understanding of the pathogenesis of periodontitis and the development of effective treatments. In this review, we discuss the phenotypes, roles, and modulating strategies of regulatory lymphocytes including Bregs and Tregs in periodontitis and frequently cooccurring inflammatory diseases such as rheumatoid arthritis, Alzheimer disease, diabetes mellitus, and stroke. The current evidence suggests that restoring immune balance through therapeutic targeting of regulatory lymphocytes is a promising strategy for the treatment of periodontitis and other systemic inflammatory diseases.
33343903 Sjögren's syndrome with nodular pulmonary amyloidosis. 2021 Jan We report a case of Sjögren's syndrome with nodular pulmonary amyloidosis. Amyloidosis is a heterogeneous group of diseases caused by aggregation of autologous protein and its extracellular deposition as fibrils. Most cases of nodular pulmonary amyloidosis are the result of an underlying disorder such as mucosa-associated lymphoid tissue lymphoma, rheumatoid arthritis, or multiple myeloma. Nodular pulmonary amyloidosis with Sjögren's syndrome is very rare. The clinical outcome of patients with nodular pulmonary amyloidosis is good if the underlying disease can be controlled.
35415103 Ochronotic Surprise during Total Knee Replacement! A Case Report. 2021 Oct INTRODUCTION: Alkaptonuria is a rare autosomal recessive metabolic disorder characterized by accumulation of homogentisic acid (HGA) due to an inherited deficiency of the enzyme HGA oxidase. Unlike rheumatoid arthritis which affects the small joints of the hands and feet, ochronotic arthropathy predominantly involves the large weight-bearing joints such as hips, knees, and spine. The knee is the most common joint to be affected. Ochronotic arthropathy is usually managed conservatively, but for severely affected hip and knee joints, replacement is considered. CASE REPORT: This report describes a case of 57-year-old male who presented with bilateral knee osteoarthritis who was incidentally diagnosed with ochronosis intraoperatively during total knee arthroplasty, its challenges faced and post-operative functional outcome after 18 months follow-up. CONCLUSION: This case report highlights the need for high index of suspicion for preoperative diagnosis of ochronotic arthropathy. Difficult spinal anesthesia should be anticipated. Friable and stiff tendon due to ochronotic involvement can put the extensor tendon at risk of rupture during retraction of patella intraoperatively. Post-operative active quadriceps rehabilitation should be done with caution due to friable tendon.
35046347 [A Case of Malignant Thyroid Lymphoma That Was Difficult to Differentiate from Methotrexat 2021 Dec A female patient in her 60s was going to get treatment for rheumatoid arthritis(RA). Considering the possibility of using biologics, CT examination was performed for screening of malignant diseases. A mass shadow in the left lobe of the thyroid gland was detected. The patient was followed up, and ultrasonography did not reveal any malignant findings. She was treated with methotrexate(MTX), and 1 year later, the thyroid mass was enlarged on CT. Ultrasonography revealed an enlarged hypoechoic region. Fine needle aspiration cytology revealed malignant lymphoma. Excisional biopsy was performed to determine the treatment plan. The pathological diagnosis was follicular lymphoma, and the possibility of methotrexate- associated lymphoproliferative disorders(MTX-LPD)persisted. It was difficult to discontinue MTX because of the high activity of RA. She was treated with rituximab for malignant lymphoma and concurrently with MTX for RA. The thyroid tumor disappeared for 3 months. Four years later, there is no sign of tumor recurrence.
34970926 Cryptococcal Prostatitis Forming Caseous and Suppurative Granulomas Diagnosed by Needle Bi 2021 Dec 31 Cryptococcal granulomatous prostatitis is extremely rare, and there have been few reports of its diagnosis by prostate needle biopsy. The patient, an 81-year-old man, was receiving immunosuppressive treatment for rheumatoid arthritis. He had an oropharyngeal ulcer, and it was diagnosed alongside a methotrexate-related diffuse large B-cell lymphoma. A systemic imaging examination revealed a prostatic tumor-like mass clinically suspected to be prostatic cancer, and a needle biopsy was performed. The biopsy specimen showed various types of inflammatory cell infiltration, and suppurative granuloma and caseous granuloma were observed. Both granulomas showed multiple round and oval organisms that were revealed with Grocott methenamine silver staining. Acid-fast bacilli were not detected by Ziehl-Neelsen staining. We histologically diagnosed granulomatous prostatitis caused by Cryptococcus infection. Caseous granulomas often develop in the prostate after bacillus Calmette-Guerin immunotherapy for bladder cancer, although the possibility of cryptococcal granulomatous prostatitis should also be considered.
34754561 A combined approach for stabilization and endoscopic/ endonasal odontoid and clivus resect 2021 BACKGROUND: Basilar invagination (BI) is a complex condition characterized by prolapse of the odontoid into the brain stem/upper cervical cord. This lesion is often associated with Chiari malformations, and rheumatoid arthritis (RA). Treatment options for BI typically include cervical traction, an isolated anterior transoral odontoidectomy, anterior endonasal odontoidectomy, an isolated posterior fusion, or combined anterior/ posterior surgical approach. CASE DESCRIPTION: A 45-year-old female with a Chiari I malformation and RA underwent a combined posterior C0-C5 posterior decompression/fusion, followed by an anterior odontoidectomy (i.e. endoscopic/endonasal under neuronavigation). Postoperatively, the patient's symptoms and neurological signs resolved. CONCLUSION: BI in was successfully managed with a combined posterior C0-C5 decompression/fusion followed by an anterior endoscopic/endonasal odontoidectomy performed under neuronavigation.
34374653 The influence of polyphenol-rich extracts on the production of pro-inflammatory mediators 2021 Apr Recent decades have seen a rise in chronic inflammatory diseases such as diabetes, cardiovascular diseases, asthma, rheumatoid arthritis, neurodegenerative diseases. Importantly, such chronic inflammatory diseases also increase the risk of cancer development and there is a pressing need to identify new anti-inflammatory drugs. One promising source of new medication are natural polyphenolic compounds and polyphenol-rich preparations, extracts and foods, which have strong antioxidant properties. This paper reviews the anti-inflammatory role of polyphenolic-rich natural extracts, and their ability to modulate crucial pro-inflammatory mediators, such as cyclooxygenase-2, prostaglandin E(2), inducible nitric oxide synthase, and nitric oxide, in macrophage cells. Our research confirms that natural compounds have health potential, and could be used in the treatment or prevention of inflammatory diseases.