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ID PMID Title PublicationDate abstract
29257274 MicroRNA‑33 regulates the NLRP3 inflammasome signaling pathway in macrophages. 2018 Feb The nucleotide binding domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome/interleukin (IL)-1β axis serves an essential role in regulating the development of rheumatoid arthritis (RA). The dysregulation of cellular metabolism, such as mitochondrial dysfunction, results in the activation of the NLRP3 inflammasome. microRNA (miR)‑33 has previously been identified to be a regulator of lipid metabolism and mitochondrial function. However, whether miR‑33 regulates the NLRP3 inflammasome/IL‑1β axis remains unknown. In the present study, it was observed that an miR‑33 mimic or anti‑miR‑33 markedly stimulated or inhibited, respectively, IL‑1β protein expression levels in mouse peritoneal macrophages. Mechanistically, miR‑33 upregulated the expression of NLRP3 mRNA and protein as well as caspase‑1 activity in primary macrophages. In addition, the results demonstrated that miR‑33 impaired mitochondrial oxygen consumption rates, resulting in the accumulation of cellular reactive oxygen species, which stimulated NLRP3 expression, caspase‑1 activity and IL‑1β secretion. The results of the present study demonstrated that miR‑33 levels and NLRP3 inflammasome activity were increased in peripheral blood monocytes from patients with RA patients compared with healthy donors. In conclusion, the present study identified miR‑33 to be a positive regulator of the NLRP3 inflammasome in macrophages. The miR‑33/NLRP3 inflammasome pathway may therefore be involved in RA development.
29251350 Engineered cell migration to lesions linked to autoimmune disease. 2018 Apr The damaging and degenerative effects in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn's disease often manifests as the formation of lesions that feature a high local concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF along with other pro-inflammatory factors form a positive feedback loop that ultimately perpetuate the lesions. Hence, to engineer chemotaxis to GM-CSF, we created a new chimeric GM-CSF receptor alpha subunit (GMRchi) that was coupled with a previously engineered Ca(2+) -activated RhoA. When these proteins were expressed in mammalian cells, it allowed migration to chemical and cellular sources of GM-CSF. As a possible therapeutic intervention, we further implemented the mechanism of cell-cell membrane fusion and subsequent death. Since the microenvironment of lesions is more than just GM-CSF secretion, the further ability to recognize a combination of other features such as tissue markers will be needed for greater specificity. Nonetheless, this work represents a first step to enable cell-based therapy of autoimmune lesions.
28992800 Antimalarial-induced cardiomyopathy: a systematic review of the literature. 2018 Apr Background Antimalarials (AMs) are widely used in the treatment of connective tissue diseases. Their main side effect is retinal damage, while heart disease has been described in isolated cases. The aim of this study is to systematically review the existing literature on AM-induced cardiomyopathy (AMIC). Methods The PubMed database was searched for heart biopsy-confirmed AMIC cases. Information on demographics, clinical presentation, concomitant AM-related toxicity, cardiological investigations, treatment and outcome were collected. Descriptive statistics were used. Results Forty-seven cases (42 females) were identified with a mean age at diagnosis 56.4 ± 12.6 and mean AM treatment duration 12.7 ± 8.2 years. Systemic lupus erythematosus ( n = 19) and rheumatoid arthritis ( n = 18) were the most common primary diseases. Clinical presentation was that of congestive heart failure in 77%, while eight patients presented with syncope (17%). Complete atrioventricular block was reported in 17 patients; 24 received a permanent pacemaker (51%). Impaired systolic function was detected in 52.8%, bi-ventricular hypertrophy in 51.4% and restrictive filling pattern of the left ventricle in 18 patients. Cardiac magnetic resonance showed late gadolinium enhancement in seven cases, with a non-vascular pattern in the interventricular septum. Cardiomyocyte vacuolation was reported in all cases; intravacuolar lamellar and curvilinear bodies were observed in 46 (98%) and 42 (89.4%) respectively. Mortality rate was 45% (18/40). Conclusion AMIC is a rare, probably under-recognized, complication of prolonged AM treatment. It presents as a hypertrophic, restrictive cardiomyopathy with or without conduction abnormalities. Early recognition and drug withdrawal are critical with a survival rate of almost 55%.
30464652 Mixed connective tissue disease complicated by heart failure in Ile-Ife, Nigeria: manageme 2018 BACKGROUND: Mixed connective tissue disease (MCTD; also known as Sharp's syndrome) is a rare autoimmune inflammatory disorder characterized by high titer of U1 ribonucleoprotein (U1RNP) antibody and clinical and serological overlap of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis is based on clinical and serological factors in criteria such as Alarcon-Segovia, Khan, Kusakawa, and Sharps. Cardiac disease can be a complication of connective tissue disease (CTD). There are few reports in Africa. AIMS: To present MCTD as underlying cause of heart failure with reduced ejection fraction and highlight challenges of investigations and treatment. OBJECTIVES: To highlight the first case in our center and discuss the cardiac, respiratory, and rheumatologic management. PATIENT AND METHODS: We present a 52-year-old woman with 3 weeks history of productive cough with whitish sputum, severe dyspnea, orthopnea, paroxysmal nocturnal dyspnea, right sided abdominal pain, leg swellings, a one year history of recurrent fever, Raynaud's phenomenon, small joint swellings and deformities with pain in both hands. RESULTS: On examination there was microstomia, tethered forehead and lower eyelid skin, tender swelling of the interphalangeal joints and arthritis mutilans. Laboratory findings showed estimated glomerular filtration rate <60 mL/kg/min/1.73 m(2), U1RNP antibody levels were eight times upper limit of normal, elevated rheumatoid factor, speckled antinuclear antibody pattern, negative anticentromere antibody, anti Scl-70 and anticyclic citrullinated peptide. Chest X-ray/CT revealed pulmonary fibrosis. Echocardiography findings showed reduced ejection fraction of 40%, elevated pulmonary arterial pressure at rest of 60.16 mmHg. The patient showed improvement on antifailure drugs, but prednisolone was stopped for sudden reversal of previously controlled stage 2 hypertension (HTN), and the patient was discharged in a stable condition. Difficulties ensued in obtaining prompt definite results due to the unavailability of serologic tests in the hospital, and the tests were done outside the state and country. CONCLUSION: Identifying MCTD is critical, especially in patients requiring steroids that may worsen systemic HTN and heart failure. There is a need to have definitive investigative facilities for such patients in hospitals.
30026507 Endometriosis. 2018 Jul 19 Endometriosis is a common inflammatory disease characterized by the presence of tissue outside the uterus that resembles endometrium, mainly on pelvic organs and tissues. It affects ~5-10% of women in their reproductive years - translating to 176 million women worldwide - and is associated with pelvic pain and infertility. Diagnosis is reliably established only through surgical visualization with histological verification, although ovarian endometrioma and deep nodular forms of disease can be detected through ultrasonography and MRI. Retrograde menstruation is regarded as an important origin of the endometrial deposits, but other factors are involved, including a favourable endocrine and metabolic environment, epithelial-mesenchymal transition and altered immunity and inflammatory responses in genetically susceptible women. Current treatments are dictated by the primary indication (infertility or pelvic pain) and are limited to surgery and hormonal treatments and analgesics with many adverse effects that rarely provide long-term relief. Endometriosis substantially affects the quality of life of women and their families and imposes costs on society similar to those of other chronic conditions such as type 2 diabetes mellitus, Crohn's disease and rheumatoid arthritis. Future research must focus on understanding the pathogenesis, identifying disease subtypes, developing non-invasive diagnostic methods and targeting non-hormonal treatments that are acceptable to women who wish to conceive.
29805314 Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Curren 2018 The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS.
29760711 Selective Modulation of TNF-TNFRs Signaling: Insights for Multiple Sclerosis Treatment. 2018 Autoimmunity develops when self-tolerance mechanisms are failing to protect healthy tissue. A sustained reaction to self is generated, which includes the generation of effector cells and molecules that destroy tissues. A way to restore this intrinsic tolerance is through immune modulation that aims at refurbishing this immunologically naïve or unresponsive state, thereby decreasing the aberrant immune reaction taking place. One major cytokine has been shown to play a pivotal role in several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS): tumor necrosis factor alpha (TNFα) modulates the induction and maintenance of an inflammatory process and it comes in two variants, soluble TNF (solTNF) and transmembrane bound TNF (tmTNF). tmTNF signals via TNFR1 and TNFR2, whereas solTNF signals mainly via TNFR1. TNFR1 is widely expressed and promotes mainly inflammation and apoptosis. Conversely, TNFR2 is restricted mainly to immune and endothelial cells and it is known to activate the pro-survival PI3K-Akt/PKB signaling pathway and to sustain regulatory T cells function. Anti-TNFα therapies are successfully used to treat diseases such as RA, colitis, and psoriasis. However, clinical studies with a non-selective inhibitor of TNFα in MS patients had to be halted due to exacerbation of clinical symptoms. One possible explanation for this failure is the non-selectivity of the treatment, which avoids TNFR2 stimulation and its immune and tissue protective properties. Thus, a receptor-selective modulation of TNFα signal pathways provides a novel therapeutic concept that might lead to new insights in MS pathology with major implications for its effective treatment.
29729445 Emerging role of IL-35 in inflammatory autoimmune diseases. 2018 Jul Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis. In addition, functional analysis suggested that IL-35 is critical in the onset and development of these diseases. Therefore, the present study will systematically review what had been occurred regarding IL-35 in inflammatory autoimmune disease. The information collected will help to understand the biologic role of IL-35 in immune cells, and give information about the therapeutic potential of IL-35 in these diseases.
29714437 The association of neuropathic pain and disease activity, functional level, and quality of 2018 Apr 30 Background/aim: Increased neuropathic pain (NP) symptoms are seen in rheumatologic diseases such as fibromyalgia, osteoarthritis, and rheumatoid arthritis, but no studies have demonstrated a relationship between ankylosing spondylitis (AS) and NP except for a brain imaging study. The aim of this study was to estimate the presence of NP in patients with AS and to investigate how NP was related to disease activity, functional status, and quality of life. Materials and methods: A total of 100 AS patients (71 males and 29 females; median age: 37 years, range: 18–71 years) were included in the study. Pain (visual analog scale (VAS) and the painDETECT questionnaire), disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Patient Global Assessment of Disease Activity (PGA), and Ankylosing Spondylitis Disease Activity Score (ASDAS)), functional level (Bath Ankylosing Spondylitis Functional Index (BASFI)), and health-related quality of life (36-Item Short Form Survey (SF-36)) were evaluated. Patients were divided into two groups. Group 1 included patients with possible or likely NP symptoms (painDETECT score of ≥13) and Group 2 included patients without NP symptoms (painDETECT score of <13). Results: Low back pain-VAS, peripheral joint-VAS, BASDAI, PGA, ASDAS, and BASFI scores were significantly higher in Group 1 compared to those of Group 2 (P < 0.05). The SF-36 physical component (PC) score was significantly lower in Group 1 compared to that of Group 2 (P < 0.05). There were no significant differences between the groups regarding SF-36 mental component (MC) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) values and MASES scores. Total painDETECT scores correlated positively with low back pain-VAS, peripheral joint-VAS, morning stiffness-VAS, BASDAI, ASDAS-CRP, ASDAS-ESR, PGA, BASFI, and MASES scores and ESR values, and inversely with SF-36 PC scores. Conclusion: Our results suggest that AS patients should be evaluated in terms of NP in order not to underestimate NP. If clinicians find evidence of likely NP, they should treat the patient with drugs that target NP.
29676099 [Binding interaction of harpagoside and bovine serum albumin: spectroscopic methodologies 2018 Mar Scrophularia ningpoensis has exhibited a variety of biological activities and been used as a pharmaceutical product for the treatment of inflammatory ailment, rheumatoid arthritis, osteoarthritis and so on. Harpagoside (HAR) is considerer as a main bioactive compound in this plant. Serum albumin has important physiological roles in transportation, distribution and metabolism of many endogenous and exogenous substances in body. It is of great significance to study the interaction mechanism between HAR and bovine serum albumin (BSA). The mechanism of interaction between HAR and BSA was investigated using 2D and 3D fluorescence, synchronous florescence, ultraviolet spectroscopy and molecular docking. According to the analysis of fluorescence spectra, HAR could strongly quench the fluorescence of BSA, and the static quenching process indicated that the decrease in the quenching constant was observed with the increase in temperature. The magnitude of binding constants (KA) was more than 1×10⁵ L·mol⁻¹, and the number of binding sites(n) was approximate to 1. The thermodynamic parameters were calculated through analysis of fluorescence data with Stern-Volmer and Van't Hoff equation. The calculated enthalpy change (ΔH) and entropy change (ΔS) implied that the main interaction forces of HAR with BSA were the bonding interaction between van der Waals forces and hydrogen. The negative values of energy (ΔG) demonstrated that the binding of HAR with BSA was a spontaneous and exothermic process. The binding distance(r) between HAR and BSA was calculated to be about 2.80 nm based on the theory of Frster's non-radiation energy transfer, which indicated that energy is likely to be transfer from BSA to HAR. Both synchronous and 3D florescence spectroscopy clearly revealed that the microenvironment and conformation of BSA changed during the binding interaction between HAR and BSA. The molecular docking analysis revealed HAR is more inclined to BSA and human serum albumin (HSA) in subdomain ⅡA (Sudlow's site I). This study will provide valuable information for understanding the action mechanism of HAR.
29649564 XBP1 activation enhances MANF expression via binding to endoplasmic reticulum stress respo 2018 Jun As an endoplasmic reticulum (ER) stress-related protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) is involved in inflammatory diseases, such as rheumatoid arthritis. However, the mechanisms of the transcriptional regulation of MANF is still undefined. Here, we showed that MANF expression was upregulated in hepatitis B tissues and hepatoma cells, and positively correlated with the spliced X-box binding protein-1 (XBP1s). Both overexpression of XBP1s and tunicamycin treatment were able to enhance MANF transcription. On the contrary, inhibition of XBP1 splicing by IRE1α endonuclease inhibitor or knockdown of XBP1s with siRNA attenuated MANF expression. Two ER stress-responsive elements (ERSE) were found in the promoter region of MANF (ERSE I and ERSE II). The chromatin immunoprecipitation and reporter gene assay showed that XBP1s mainly binds to ERSE I to promote MANF transcription. Moreover, MANF was found to interact with XBP1s to enhance its own expression. Our findings uncover a new mechanism of ERSE-dependent transcriptional regulation of MANF, as well as a key role of XBP1s in promoting the MANF expression.
29619934 Assessing synovitis with conventional static and dynamic contrast-enhanced magnetic resona 2018 Apr Knee osteoarthritis (KOA) is one of the most common causes of physical disability in the elderly population. With an increasing ageing and obese population, the prevalence of KOA is expected to rise substantially. The needs for a better understanding of the disease and tools that can predict the course of the disease, for example following treatment, are therefore imperative. 

Inflammation has over the last years been recognised as an important factor for both the symptomatology and disease course in KOA. Synovitis, inflammation of the synovium, is the hallmark of intra-articular inflammation and has been associated with pain, symptoms and disease progression. Synovitis can be visualised on conventional static MRI. However, the addition of a dynamic contrast-enhanced (DCE) MRI-sequence enables the assessment of the synovium both in regards of its morphology and perfusion. Studies in both KOA and rheumatoid arthritis have shown that DCE-MRI measures of synovitis are more sensitive than conventional static MRI in regards of microscopic synovitis and patient-reported outcome measures (PROMs).

 The aims of this PhD project were to characterise synovitis in KOA with conventional static and DCE MRI in regards of histology (study I), its association with PROMs (studies II-III) and changes following a symptoms-improving intervention (study III). We found that DCE-MRI-measures of synovitis seem to be superior to conventional static MRI in their association with histological synovitis (study I) and pain (study II) in a cross-sectional setting. However, the use of DCE-MRI over conventional static CE-MRI cannot be justified when assessing the long-term changes in synovitis following an intervention with intra-articular corticosteroids/placebo and exercise (study III). 

Evidence is mounting that KOA is constituted of different phenotypes. There is an urgent need to define these in order to improve and individualise treatment and management. It is essential to gain a better understanding of the different pro-cesses taking place in KOA, on an individual level and in the different stages of the disease. DCE-MRI may very well be a useful tool in facing these challenges especially in regards of the role of perfusion and inflammation in KOA and osteoarthri-tis in general.
29410154 Antinociceptive and anti-inflammatory activities of a standardizedextract of bis-iridoids 2018 Apr 24 ETHNOPHARMACOLOGICAL RELEVANCE: Pterocephalus hookeri (C.B. Clarke) Höeck, one of the most popular Tibetan herbs, has been widely applied in Tibetan medicine prescriptions. Chemical investigations have led to the isolation of many bis-iridoids. However, the pharmacological activities of bis-iridoid constituents of this plant have never been reported before. AIM OF THE STUDY: This study evaluated the anti-inflammatory and analgesic activities of afraction of bis-iridoid constituents of P. hookeri (BCPH) in order to provide experimental evidence for its traditional use, such as for cold, flu, and rheumatoid arthritis. MATERIALS AND METHODS: The analgesic effects of BCPH were investigated using the hot-plate test and acetic acid-induced writhing test. The anti-inflammatory activities were observed using the following models: carrageenin-induced edema of the hind paw of rats and xylene-induced ear edema in mice. The effects of dexamethasone administration were also studied. RESULTS: BCPH significantly increased the hot-platepain threshold and reduced acetic acid-induced writhing response in mice. Moreover, BCPH remarkably inhibited xylene-induced ear edema and reduced the carrageenin-induced rat paw edema perimeter. CONCLUSION: The results reveal that BCPH has central, peripheral analgesic activities as well as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.
29101724 Adjunctive role of self-retained cryopreserved amniotic membrane in treating immune-relate 2018 Oct PURPOSE: To present a case of successful treatment of immune-related severe dry eye disease (DED) by self-retained cryopreserved amniotic membrane (CAM) in conjunction with conventional and systemic immunotherapy. OBSERVATIONS: A 48-year-old female with a 10-year history of rheumatoid arthritis under systemic immunomodulation developed non-resolved severe ocular dryness, pain, photophobia and blurred vision due to corneal epithelial keratopathy OD much worse than OS despite topical artificial tears, steroids, cyclosporine, autologous serum drops, punctal plugs and scleral lens for the last 3 years. During the first year, she received punctal cauterization and a total of 6 CAM, each for an average of 7.2 ± 2.3 days, for recurrent diffuse superficial punctate keratitis (SPK) with filaments to achieve an average symptom-free period of 2.4 ± 0.9 months and visual acuity improvement from 20/400 to 20/200. During the next 2 years, she received surgical closure of puncta for recurrent punctal reopening, additional systemic immunomodulation and a total of 4 CAM, each for an average of 8.5 ± 2 days, for recurrent scattered SPK, to achieve an average symptom-free period of 6.4 ± 1 months and visual acuity improvement from 20/200 to 20/70. CONCLUSIONS: Self-retained CAM can be an adjunctive treatment for immune-related DED, which is refractory to conventional and systemic immunotherapies.
29049933 Systemic autoimmune diseases are associated with an increased risk of bipolar disorder: A 2018 Feb BACKGROUND: Studies suggested autoimmunity plays a role in the etiology of bipolar disorder (BD). This study aimed to investigate the association between systemic autoimmune diseases (SADs) and the subsequent development of BD, and examine the potential risk factors for developing BD. METHODS: Patients with SADs were identified in the Taiwan National Health Insurance Program (NHIP). A comparison cohort was created by matching patients without SADs with age. The SADs cohort consisted of 65,498 while the comparison cohort consisted of 261,992 patients. The incidence of BD was evaluated in both cohorts. RESULTS: The major finding was the discovery of a higher incidence of subsequent BD among patients with SADs (adjusted hazard ratio: 1.98). Specifically, the risk of BD was observed to be significant increase in systemic lupus erythematosus, rheumatoid arthritis, autoimmune vasculitis, Sicca syndrome and Crohn's disease. Furthermore, our study revealed some potential risk factors for developing BD including female, younger age and patients who lived in eastern Taiwan. Also, some comorbidities including dyslipidemia, chronic obstructive pulmonary disease, diabetes mellitus, asthma, cerebrovascular disease, alcohol used disorder, liver cirrhosis, and malignancies were potential risk factors for incident BD. LIMITATIONS: The diagnosis of SADs was based on the catastrophic illness certificate defined by Taiwanese NHIP. Thus, not every form of SADs was explored for subsequent developing BD. CONCLUSION: This study confirms that SADs are associated with higher incidence of BD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.
28988826 Clinical diagnostic tools for vitamin D assessment. 2018 Jun Vitamin D deficiency has been implicated in a plethora of diseases including rheumatoid arthritis, Parkinson's disease, Alzheimer's disease, and osteoporosis. Deficiency of this vitamin is a global epidemic affecting both developing and developed nations. Within a clinical context, the qualitative and quantitative analysis of vitamin D is therefore vital. The main metabolic markers for assessing vitamin D status in humans are the hydroxylated forms of vitamin D, 25OHD(3) and 25OHD(2) on account of their long half-lives within the body and excellent stability. An adequate level for healthy individuals of these hydroxylated forms is estimated to be around 20-40ng/ml of blood. There are three main analytical techniques for determining the levels of 25OHD(3) and 25OHD(2). The first technique is immunoassay-based and can be performed in a rapid, high throughput, automated manner, allowing as many as 240 tests per hour with the duration of each assay as little as 18min. Furthermore, it offers excellent sensitivity with a detection range of 3.4-156ng/ml. A major downside of immunoassays is that they are unable to distinguish between the various forms of vitamin D. While HPLC is a highthroughput low cost instrument it is not a very sensitive technique and cannot quantify the down stream metabolites of vitamin D. The third technique, namely liquid chromatography-mass spectrometry (LC-MS/), provides excellent sensitivity with a wide dynamic range from 0.068pg/ml to 100ng/ml. Additionally, it offers a high level of separation and permits identification of vitamin D-related metabolites. However, a huge limitation with LC/MS/MS is their poor throughput for sample analyses. As yet, there is no analytical technique which combines the fine detection capabilities of LC/MS/MS and the rapid, automated format of immunoassay, for vitamin D analyses. Future attention therefore needs to be given to this area if the current clinical diagnostic tools for vitamin D analysis are to be further improved.
30839692 A microfluidic chip-based co-culture of fibroblast-like synoviocytes with osteoblasts and 2018 Sep Targeting fibroblast-like synoviocyte (FLS) migration and invasion-mediated bone erosion is a promising clinical strategy for the treatment of rheumatoid arthritis (RA). Drug sensitivity testing is fundamental to this scheme. We designed a microfluidic chip-based, cell co-cultured platform to mimic RA FLS-mediated bone erosion and perform drug-sensitive assay. Human synovium SW982 cells were cultured in the central channel and migrated to flow through matrigel-coated side channels towards cell culture chamber where RANKL-stimulated osteoclastic RAW264.7 and osteogenic medium (OS)-stimulated bone marrow mesenchymal stem cells (BMSC) were cultured in the microfluidic chip device, mimicking FLS migration and invasion-mediated bone erosion in RA. These SW982 cells showed different migration potentials to osteoclasts and BMSC. The migration of SW982 cells with high expression of cadherin-11 was more potent when SW982 cells were connected with the co-culture of RAW264.7 and BMSC. Simultaneously, in the co-cultured chamber, tartrate-resistant acid phosphatase (TRAP) activity of RANKL-stimulated RAW264.7 cells was enhanced, but alkaline phosphatase (ALP) activity was decreased in comparison with mono-cultured chamber. Furthermore, it was confirmed that celastrol, a positive drug for the treatment of RA, inhibited SW982 cell migration as well as TRAP activity in the cell-cultured microfluidic chips. Thus, the migration and invasion to bone-related cells was reconstituted on the microfluidic model. It may provide an effective anti-RA drug screen model for targeting FLS migration-mediated bone erosion.
30588552 Clinical features of hypertrophic pachymeningitis in a center survey. 2019 Mar BACKGROUND: Hypertrophic pachymeningitis (HP) is characterized by cranial and/or spinal thickening of the dura mater with or without associated inflammation. Neuroimaging studies reveal dura mater thickening and focal or diffuse contrast enhancement. It is described in association with trauma, infections, tumors, autoimmune/inflammatory diseases, and cerebrospinal fluid hypotension syndrome, with some cases remaining idiopathic. METHODS: A retrospective study was conducted with patients' identification through a key terms search within MRI reports in the period of July 2008 to September 2015. Clinical files, MRI, laboratory, and pathology data were reviewed. RESULTS: Fifty-three patients were identified and 20 were excluded because they did not meet the inclusion criteria. Of the 33 included, 19 were female, with a mean age at symptoms onset of 51.2 ± 17.6 years. The most common presenting symptoms were headache and cranial nerves palsy, followed by seizures, delirium, lumbar pain, cognitive decline, motor deficit, and language impairment. In 17 patients, a neoplastic etiology was identified; in eight, inflammatory/autoimmune; in six, infectious; and two were classified as idiopathic. Of the eight patients with inflammatory/autoimmune etiology, four had possible IgG4-related disease (IgG4-RD) and the remaining had granulomatosis with polyangiitis, sarcoidosis, rheumatoid arthritis, and Tolosa-Hunt syndrome. Treatment was directed according to the underlying etiology. DISCUSSION: In the described series, a female predominance was identified, with symptoms' onset in the 5th decade. Although headache was the most common symptom, clinical presentation was varied, emphasizing the role of MRI in HP diagnosis. The underlying etiologies were diverse, with only a few cases remaining idiopathic, also reflecting the contribution of the recently described IgG4-RD.
30470476 The systematic case-referent method. 2019 Apr The systematic case-referent method is a special case-referent design originally developed for pharmacoepidemiologic research purposes. It consists in the systematic collection of series of incident cases of various disorders and the assembling of a general reference pool, from which "controls" are secondarily selected to be matched to specific cases. Both series are collected independently from each other and with no a priori hypothesis to be investigated. The reference pool can be either general or limited to a subpopulation, representative of the source population of the cases. Based on clinical recruitment of cases and referents, the design allows a very high specificity of diagnosis and documentation of clinical variables. All cases and referents are systematically documented on all treatments received before the incidence of the cases or before identification of referents. This documentation is done preferentially using objective sources assembled independently (linkage to claims data, medical records, pharmacy records, prescription records, hospital discharge letters). It can be completed with patients' interviews using standardised research tools, in particular for over-the-counter drug use and self-medication, and for the documentation of adherence to treatment and specific time-windows of exposure. Likewise, all cases and all referents are systematically documented on a series of risk factors, which are common to most epidemiological studies and are not hypothesis-dependent. Whenever the documentation of a confounding factor specific to the disease at hand is necessary, additional questionnaires can be applied to all or a sample of patients. The method has been successfully implemented for the pharmacoepidemiologic study of myocardial infarction, stroke, lupus, multiple sclerosis, rheumatoid arthritis, Guillain Barré syndrome, idiopathic thrombocytopenic purpura, type 1 diabetes mellitus, suicide attempts, breast cancer, and other disorders, for the analysis of the risk or preventing action of NSAIDs, statins, antiplatelet agents, anticoagulants, insulins, vaccines and other drugs.
30421793 Autoantibodies to killer cell immunoglobulin-like receptor 3DL1 in patients with systemic 2019 Mar A genetic variant of the killer immunoglobulin-like receptor 3DL1 (KIR3DL1) has been found in patients with systemic lupus erythematosus (SLE). Herein, we investigated the presence of autoantibodies to KIR3DL1 in a cohort of patients with SLE. We tested sera from 28 patients with SLE, 11 patients with rheumatoid arthritis (RA) and 17 healthy control subjects for anti-KIR3DL1 activity by an enzyme-linked immunosorbent assay (ELISA) using recombinant KIR3DL1-enhanced green fluorescent protein (EGFP) and EGFP proteins. Anti-KIR3DL1 antibodies were detected in 22 (79%) of the 28 patients with SLE, whereas they were present in only three (27%) of the 11 patients with RA examined. Notably, 10 (91%) of the 11 samples from patients with SLE prior to therapy had anti-KIR3DL1 antibodies. None of the samples from healthy donors were positive for the antibodies. Here, we report the presence of anti-KIR3DL1 antibodies in the sera of patients with SLE for the first time. Anti-KIR3DL1 autoantibodies may be involved in the pathogenesis of autoimmune diseases.