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ID PMID Title PublicationDate abstract
28233118 Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 2: clinical feature 2018 Jul Gout develops in four stages beginning with an asymptomatic increase in blood levels of uric acid. An acute gout attack is an expression of an underlying inflammatory process, which in the course of time is self-limiting. Without therapy monosodium urate crystals remain in the synovial fluid and synovial membrane and trigger more acute attacks. In the course of the disease monosodium urate crystals form deposits (tophi) leading in severe forms to irreversible joint deformities with loss of functionality. In 20% of cases gout leads to involvement of the kidneys. Overproduction of uric acid can cause nephrolithiasis. These stones can be composed of uric acid or calcium phosphate. Another form of kidney disease caused by gout is uric acid nephropathy. This is a form of abacterial chronic inflammatory response with deposition of sodium urate crystals in the medullary interstitium. Acute obstructive nephropathy is relatively rare and characterized by renal failure due to uric acid precipitation in the tubules because of rapid cell lysis that occurs, for example, with chemotherapy. There is a causal interdependence between the occurrence of hyperuricemia and hypertension. Uric acid activates the renin-angiotensin-aldosterone (RAA) system and inhibits nitric oxide (NO) with the possible consequence of a rise in systemic vascular resistance or arteriolar vasculopathy; however, uric acid is also an apparently independent risk factor for atherosclerosis. In contrast to young patients, the diagnosis of an acute gout attack in the elderly can be a challenge for the physician. Polyarticular manifestations and obscure symptoms can make it difficult to differentiate it from rheumatoid arthritis and calcium pyrophosphate deposition disease (CPPD). Aspiration of synovial fluid with visualization of urate crystals using compensated polarized light microscopy is the gold standard for diagnosis of acute gout. Moreover, analysis of synovial fluid enables a distinction from septic arthritis by Gram staining and bacterial culture. Soft tissue ultrasonography is useful to detect affected synovial tissue and monosodium urate crystals within the synovial fluid. Involvement of bone occurs relatively late in the disease so that x‑ray images are not useful in the early stages but might be helpful in differential diagnostics. Dual energy computed tomography (CT) and magnetic resonance imaging (MRI) can be used for certain indications.
29455266 Inflammatory tenosynovitis and enthesitis induced by immune checkpoint inhibitor treatment 2018 Apr Reports about immune-related adverse events (IrAEs) induced by immune checkpoint inhibitors (ICIs) have been increasing. Although the importance of understanding joint involvement and myalgia as an IrAE has grown, little is known about its characteristics. The aim of this study was to investigate the incidence and clinical characteristics of articular IrAEs. We reviewed 133 patients who were treated with ICIs in our institution and referred to our rheumatologic. Among them, 2 (1.5%) developed arthritis during the use of anti-PD-1 inhibitor, and there was one patient with joint pain after anti-PD-L1 inhibitor who was referred to our department from another institution. No patients had antecedent inflammatory arthritis or any relevant medical history. All 3 patients were negative for anti-nuclear antibody, rheumatoid factor, and anti-cyclic citrullinated peptide antibody. The ultrasonography showed tenosynovitis and enthesitis in both small and large joints with no or insignificant synovitis. Joint pain improved gradually within 6 months with only NSAIDs in 2 patients, and disappeared quickly in the other patient 2 weeks after 20 mg/day of predonisolone. Our report suggested diverse phenotypes of joint involvement and highlighted the importance of accumulating such patients.
30155666 Renal involvement in primary Sjogren's syndrome: a prospective cohort study. 2018 Dec The objective of the study is to prospectively evaluate the spectrum of clinical and subclinical renal involvement in patients with primary Sjogren's syndrome (pSS). Of the 174 patients screened, seventy patients with pSS underwent renal function tests, urine examination, renal ultrasound, arterial blood gases, urine pH followed by urine acidification test and renal biopsy (if indicated). Renal tubular acidosis (RTA) was treated with alkali replacement and moderate-severe tubulointerstitial nephritis (TIN) was treated with oral prednisolone. Sixty-two patients completed 1-year follow-up. A comparison was made between patients with and without renal involvement. Thirty-five (50%) patients had renal involvement. They had a lower baseline eGFR (71.85 ± 18.04 vs. 83.8 ± 17, p = 0.005). Twenty-nine patients had RTA (25 complete and 4 incomplete). Eleven patients had urinary abnormalities. Patients with RTA (n = 29) were younger (34.9 ± 9 vs. 42 ± 11.3, p = 0.006), had fewer articular (34% vs. 78%, p = 0.001) and ocular sicca (62% vs. 88%, P = 0.01) than those without RTA (n = 41) and commonly presented with hypokalemic paralysis. On biopsy, TIN (9/17) and IgA nephropathy (3/17) were most common. On follow-up, there was no clinically significant change in eGFR; however, one patient with renal calculi and incomplete distal renal tubular acidosis (dRTA) progressed to complete dRTA. Two patients treated with steroids had marginal improvement in eGFR. Renal involvement in pSS is under-recognized with the most common manifestation being RTA presenting with hypokalemic paralysis. These patients are younger with less articular and sicca symptoms. Subclinical RTA may progress to complete RTA. Renal biopsy should be considered in all patients with renal involvement.
30583473 Risk of Infection with Methotrexate Therapy in Inflammatory Diseases: A Systematic Review 2018 Dec 21 The aim of this study was to determine the risk of infection in adults with inflammatory rheumatic diseases (IRDs) treated with methotrexate. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing methotrexate versus placebo in adults using MEDLINE, EMBASE, and CENTRAL databases from 1980 to August 2017. The primary outcome was the risk of infection associated with methotrexate therapy. We chose a random effect model to summarize adverse event outcomes as risk ratios (RRs) and related 95% confidence intervals (95% CI). Twelve RCTs (total patients 1146) met the inclusion criteria for our main analysis, and ten for risk of serious infection (total patients 906). Overall, methotrexate was associated with increased risk of infection in rheumatoid arthritis (RA) (RR: 1.25; 95% CI, 1.01⁻1.56; p = 0.04; I² = 0%), but not in other non-RA IRD populations. There was no increased risk of total infections (RR: 1.14; 95% CI, 0.98⁻1.34; p = 0.10; I² = 0%) or serious infections (RR: 0.76; 95% CI, 0.11⁻5.15; p = 0.78; I² = 0%) in all included IRDs. Conclusively, methotrexate use in IRDs is associated with a higher risk of all infections in RA, but not in other non-RA (IRD) populations. There is no increased risk of serious infections.
29797173 Anti-inflammatory activity of dimethyl octenol and oleanene tetrol isolated from Trianthem 2018 Aug Dimethyl octenol from chloroform extract and oleanene tetrol from water extract of Trianthema decandra (TD) were isolated and characterized by using HPLC, UV, FT-IR, NMR, LC-MS and CHNS, their structure were elucidated from their respective spectral data. The anti-inflammatory activity of chloroform extract, water extract, dimethyl octenol and oleanene tetrol of T. decandra were studied and underlying cellular and molecular mechanisms of action were investigated in vitro and in vivo using macrophage-like cell line (RAW264.7 cells) and type II collagen induced arthritis mice models. Nitric oxide production was inhibited and TNF-α secretion was supressed in stimulated RAW cells treated with the chloroform extract and dimethyl octenol of T. decandra. Further, the chloroform and water extract, dimethyl octenol and oleanene tetrol inhibited protein denaturation and stabilized HRBC membranes in vitro. Reduction in inflammation as a measure of paw diameter was recorded in all the treated animals when compared to control animals. Catalase, peroxidase and glutathione peroxidase levels significantly increased in the joint tissue of treated groups. The possible mechanism of action of these compounds was studied using in silico molecular docking methods with phospholipase A(2) (PLA(2)), cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2) as targets. Among the three target proteins, the inhibition of the inflammatory protein PLA(2) and COX-2 towards dimethyl octenol and oleanene tetrol respectively. Our results contribute towards confirmation of the traditional use of TD and its compounds for the therapy of rheumatoid arthritis and other inflammatory joint disorders.
30202513 Periostin expression in neoplastic and non-neoplastic diseases of bone and joint. 2018 BACKGROUND: Periostin is a matricellular protein that is expressed in bone and joint tissues. To determine the expression of periostin in primary bone tumours and to assess whether it plays a role in tumour progression, we carried out immunohistochemistry and ELISA for periostin in a range of neoplastic and non-neoplastic bone and joint lesions. METHODS: 140 formalin-fixed paraffin-embedded sections of bone tumours and tumour-like lesions were stained by an indirect immunoperoxidase technique with a polyclonal anti-periostin antibody. Periostin expression was also assessed in rheumatoid arthritis (RA) and non-inflammatory osteoarthritis (OA) synovium and synovial fluid immunohistochemistry and ELISA respectively. RESULTS: Periostin was most strongly expressed in osteoid/woven bone of neoplastic and non-neoplastic bone-forming lesions, including osteoblastoma, osteosarcoma, fibrous dysplasia, osteofibrous dysplasia, fracture callus and myositis ossificans, and mineralised chondroid matrix/woven bone in chondroblastoma and clear cell chondrosarcoma. Reactive host bone at the edge of growing tumours, particularly in areas of increased vascularity and fibrosis, also stained strongly for periostin. Vascular elements in RA synovium strongly expressed periostin, and synovial fluid levels of periostin were higher in RA than OA. CONCLUSIONS: In keeping with its known role in modulating the synthesis of collagen and other extracellular matrix proteins in bone, strong periostin expression was noted in benign and malignant lesions forming an osteoid or osteoid-like matrix. Periostin was also noted in other bone tumours and was found in areas of reactive bone and increased vascularity at the edge of growing tumours, consistent with its involvement in tissue remodelling and angiogenesis associated with tumour progression.
29369232 Survey of Ophthalmologists Regarding Practice Patterns for Dry Eye and Sjogren Syndrome. 2018 Nov OBJECTIVE: To survey ophthalmologists about current practice patterns regarding the evaluation of dry eye patients and referrals for a Sjogren syndrome (SS) workup. METHODS: An online survey was sent to ophthalmologists affiliated with the Scheie Eye Institute or Wills Eye Hospital using REDCap in August 2015. Descriptive statistics were used to summarize the data. RESULTS: Four hundred seventy-four survey invitations were sent out and 101 (21%) ophthalmologists completed the survey. The common traditional dry eye test performed was corneal fluorescein staining (62%) and the most common newer dry eye test performed was tear osmolarity (18%). Half of respondents (51%) refer fewer than 5% of their dry eye patients for SS workups, with 18% reporting that they never refer any patients. The most common reasons for referrals included positive review of systems (60%), severe dry eye symptoms (51%) or ocular signs (47%), or dry eye that is refractory to treatment (42%). The majority (83%) felt that there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred for evaluation for SS. CONCLUSIONS: Ophthalmologists continue to prefer the use of traditional dry eye tests in practice, with the most common test being corneal fluorescein staining. There is an underreferral of dry eye patients for SS workups, which is contributing to the continued underdiagnosis of the disease. Most respondents felt that there was a need for an evidence-based standardized screening tool to decide which dry eye patients should be referred for SS evaluations.
29453859 Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may r 2018 Jun Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. C-X-C motif chemokine receptor 5 (CXCR5) is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand C-X-C motif chemokine ligand 13 (CXCL13). In this study we aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay. CXCR5(+) and CXCL13(+) cells in minor salivary glands were detected using immunohistochemistry. Our results demonstrated that SS-associated genetic polymorphisms affected the expression of CXCR5 (P < 0·01). Notably, a decreased percentage of CXCR5(+) cells, with lower CXCR5 expression, was observed for most circulating B and T cell subsets in SS patients, reaching statistical significance in CD19(+) CD27(+) immunoglobulin (Ig)D(+) marginal zone (P < 0·001), CD19(+) CD27(+) IgD(-) memory (P < 0·05) and CD27-IgD double-negative (P < 0·01) B cells and CD4(+) CXCR3(-) CCR6(+) Th17 cells (P < 0·05). CXCL13 levels were increased in patient plasma (P < 0·001), and immunohistochemical staining revealed expression of CXCL13 and higher numbers of CXCR5(+) cells (P < 0·0001) within focal infiltrates and interstitially in salivary glands of SS patients. In conclusion, we link a genetic susceptibility allele for SS to a functional phenotype in terms of decreased CXCR5 expression. The decrease of CXCR5(+) cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS.
30060225 Dysbiosis of the buccal mucosa microbiome in primary Sjögren's syndrome patients. 2018 Dec 1 OBJECTIVES: Environmental factors in the aetiology of primary Sjögren's syndrome (pSS) are largely unknown. Host-microbiome interaction at mucosal surfaces is presumed to be involved in the aetiopathogenesis of pSS. Here, we assessed whether the microbiome of the buccal mucosa is specific for pSS compared with symptom-controls. METHODS: The bacterial composition of buccal swab samples from 37 pSS patients, 86 non-SS sicca patients (with similar dryness symptoms to pSS patients, but not fulfilling the classification criteria) and 24 healthy controls (HCs) was determined with 16S rRNA sequencing. Multivariate Association with Linear Models was used to find associations between individual taxa and pSS, taking into account smoking and dental status. Associations were replicated in a general population cohort (n = 103). RESULTS: The buccal mucosa microbiome of pSS and non-SS sicca patients both differed from HCs. A higher Firmicutes/Proteobacteria ratio was characteristic for both pSS and non-SS sicca patients. Disease status (pSS, non-SS sicca, HCs) and salivary secretion rate contributed almost equally to the variation in bacterial composition between individuals (3.8 and 4.3%, respectively). Two taxa were associated with pSS compared with non-SS sicca patients and 19 compared with HCs. When salivary secretion rate was taken into account, no taxon was associated with pSS compared with non-SS sicca. Twelve of the 19 pSS-associated taxa were correlated with salivary secretion. CONCLUSION: Dysbiosis of the buccal mucosa microbiome in pSS patients resembles that of symptom-controls. The buccal mucosa microbiome in pSS patients is determined by a combination of reduced salivary secretion and disease-specific factors.
30277415 [Effect of a gel-type denture adhesive on unstimulated whole saliva and minor salivary gla 2018 Oct INTRODUCTION AND AIM: To determine whether the continuous use of gel-type denture adhesives influence the unstimulated whole saliva, the palatal and labial saliva flow rates, and to assess the possible changes of subjective orofacial sicca symptoms. METHOD: 28 maxillary complete denture wearing patients (average age: 70 ± 10 years) were investigated. A gel-type denture adhesive was administered to the patients for regular use during the 3 weeks of examination. A questionnaire of 16 questions was used to evaluate subjective orofacial sicca symptoms. Unstimulated whole saliva was determined by the spitting method, palatal and labial saliva flow rates were measured by the Periotron(®) device with filter paper discs at the initial, first, second and third weeks. STATISTICAL ANALYSIS: The following tests were used: subjective values - χ(2)-test; flow rates - ANOVA, paired Student's t-test. RESULTS: According to the questionnaire, the ratio or severity of xerostomia did not change. A significant increase in the subjective feeling of "saliva thickness" could be detected (p = 0.027), but the other subjective parameters remained unchanged. Palatal saliva flow rates decreased significantly by week 3 (week 0: 4.21 ± 3.96 µl/cm(2)/min; week 3: 2.21 ± 2.30 µl/cm(2)/min; p = 0.024). On the other hand, there was no significant change in the unstimulated whole saliva (week 0: 0.37 ± 0.36 ml/min; week 3: 0.39 ± 0.35 ml/min) and labial saliva (week 0: 3.99 ± 3.75 µl/cm(2)/min; week 3: 2.58 ± 3.39 µl/cm(2)/min) flow rates. CONCLUSIONS: The regular use of denture adhesives did not influence xerostomia and the majority of subjective orofacial sicca symptoms, but may cause a subjective feeling of "increased saliva thickness" and reduce palatal minor salivary gland flow rates among complete maxillary denture wearers. Orv Hetil. 2018; 159(40): 1637-1644.
29720329 Effect of dental care on the oral health of Sjögren’s syndrome patients. 2018 Mar Sjögren’s syndrome (SS) is a chronic, systemic autoimmune disease affecting the exocrine glands, particularly the salivary and lacrimal glands. Xerostomia is a major feature of this syndrome and greatly affects patient quality of life. The most typical clinical signs associated with hyposalivation are dysgeusia and dysosmia, dental caries, candidiasis, periodontal disease, gland inflammation, mucositis and oral ulcers. The aims are to investigate on Plaque Index (PI) and Gingival Index (GI) before and after dental care of SS patients. Fifty-two consecutive patients (mean age 48.9±2 years) were analysed. At T0, (baseline) T1 (3 months after T0) and T2 (6 months after T0), a Plaque Index and a Gingival Index were calculated. The statistical analysis was performed using one-way ANOVA test. If distribution was not normal, Friedman test was chosen instead of ANOVA. Dunn’s multiple comparison procedure was performed as post-hoc (IBM SPSS Statistics 21 software). A statistically significant decrease was observed both in PI and in GI between T0 and T1, T1 and T2, T0 and T2 (P less than 0.05).
29622113 Imaging of Sjögren Syndrome and Immunoglobulin G4-Related Disease of the Salivary Glands. 2018 May The salivary glands are commonly affected in systemic autoimmune disease and diseases of unknown pathogenesis. Sjögren syndrome (SjS) can be affected by other systemic diseases. Immunoglobulin G4-related disease (IgG4-RD) commonly affects salivary glands. Imaging findings are usually nonspecific; however, radiologists should be familiar with the manifestations to avoid diagnostic delay. Findings of early-stage SjS are difficult to identify on routine computed tomography or MR imaging. Chronic SjS can be diagnosed from MR imaging and sialographic findings. Multiglandular and localized involvement of IgG4-RD is difficult to differentiate from malignant lymphoma for multiglandular disease and salivary gland carcinoma for localized disease.
29243055 Population-based study suggests an increased risk of Alzheimer'sdisease in Sjögren's synd 2018 Apr This population-based study was designed to estimate and compare the risk of Alzheimer's disease (AD) between patients with primary Sjögren's syndrome (SS) and non-SS patients during a 10-year follow-up period. This is a retrospective cohort study. Data were obtained from the Taiwan's National Health Insurance Research Database. We identified 4463 primary SS patients and 22,315 non-SS patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied to identify the subsequent manifestation of AD. Cox proportional hazard regression was used to study the subsequent manifestation of AD, and Kaplan-Meier survival curves were used to compare survival probability. During the 10-year follow-up period, 7 primary SS and 13 non-SS patients developed AD. During the 10-year follow-up period, the risk of AD was 2.68-fold higher in the primary SS cohort with an overall adjusted hazard ratio (HR) of 2.69 (95% CI 1.07-6.76), after adjusting for demographics and comorbidities. Within the 10-year period, patients with primary SS showed a 2.69-fold increased risk of developing AD. This risk increases with time, and the relative risk of AD is higher in older patients with primary SS.
28725949 Tubulointerstitial nephritis-induced hypophosphatemic osteomalacia in Sjögren's syndrome: 2018 Jan Sjögren's syndrome (SS) is a chronic autoimmune inflammatory disease that typically affects the salivary and lacrimal glands. Renal involvement is relatively uncommon and may precede other complaints. Tubulointestitial nephritis (TIN) is the most common renal involvement in SS. Osteomalacia occurring as the first manifestation of renal tubular disorder due to SS is very rare. We report a 39-year-old male who presented with polydipsia, polyuria, and multiple bone pain. Bone density test showed severe osteoporosis, and laboratory findings suggested hypokalemia, hypophosphatemia, and vitamin D deficiency, which supported the diagnosis of hypophosphatemic osteomalacia. He had nephrogenic loss of phosphate and potassium, tubular acidification, and concentration dysfunction. And, the diagnosis of chronic TIN was subsequently confirmed by renal biopsy. The patient reported dry mouth and physical examination showed multiple dental caries. Xerophthalmia, abnormal morphology, and function of the salivary glands by sonography and scintigraphy, together with positive anti-SSA and anti-SSB, confirmed the diagnosis of SS. The TIN indicated SS as the underlying cause of osteomalacia. After taking supplements of potassium, phosphate, vitamin D, and sodium bicarbonate for 1 month, bone pain was alleviated and serological potassium and phosphorus were also back to normal. In conclusion, renal involvement in SS may be latent and precede the typical sicca symptoms. Osteomalacia can be the first manifestation of renal disorder due to SS. Therefore, autoantibody investigations as well as the lacrimal and salivary gland examinations for SS should be considered and performed for suspected patients.
29754950 Oral health-related quality of life in primary Sjögren's syndrome. 2020 Mar OBJECTIVE: To assess health-related quality of life (HRQoL) and oral health-related quality of life, and correlate them with unstimulated whole salivary flow (UWSF) and oral sicca symptoms in patients with primary Sjögren's syndrome (PSS). METHODS: We included 60 patients with PSS and 60 healthy controls matched according to gender and age (±3 years). We measured the UWSF and scored the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI). We assessed the short version of the SF-36 as a generic measurement of HRQoL and the Xerostomia Quality of Life Scale (XeQoLS) questionnaire to evaluate oral quality of life. We evaluated oral symptoms using an 8-item Visual Analogue Scale (VAS) questionnaire. RESULTS: We observed a poorer HRQoL (lower scores in SF-36) and oral quality of life (higher scores in XeQoLS), as well as a greater severity of symptoms in the VAS questionnaire upon comparing patients vs. controls. The XeQoL correlated with the UWSF (τ = -0.24, P = .008), the ESSPRI (τ =0.45, P = .0001), VAS 1-2 and VAS 5-8 and the SF-36 score (τ = -0.28, P = .002). CONCLUSIONS: Patients with PSS had a poorer HRQoL and oral quality of life than controls. UWSF contributes to the oral quality of life which, in turn, has an impact on HRQoL. Symptomatic treatment of xerostomia as well as the prevention of infections, decay and tooth loss would help to improve the oral quality of life in these patients.
30269092 Severe calcium pyrophosphate dihydrate deposition disease of the metacarpophalangeal joint 2018 Sep 28 We report a case of calcium pyrophosphate deposition disease (CPPD) with an unusual presentation of severe chondrocalcinosis with atypical large burden deposited in the metacarpophalangeal joints as well as more typical deposition in wrists and knees as demonstrated on plain radiographs. A 77-year-old African-American woman 1-year status post parathyroidectomy for hyperparathyroidism initially presented to the rheumatology clinic to treat suspected rheumatoid arthritis given her pattern of joint involvement but was found to have CPPD. The patient's history is notable for end-stage renal disease which complicates medical management. This case illustrates radiographic findings of CPPD and explores the challenges of treating CPPD in the setting of comorbid conditions.
30193264 Out-of-Pocket Costs for Infliximab and Its Biosimilar for Rheumatoid Arthritis Under Medic 2018 Sep 4 This study estimates mean 2017 total and out-of-pocket costs for infliximab and its biosimilar infliximab-dyyb under Medicare Part D.
30146741 Emerging role of metabolomics in rheumatology. 2018 Aug The pursuit for understanding disease pathogenesis, in this age of rapid laboratory diagnostics and fast-paced research, has led scientists worldwide to take recourse in hypothesis-free approaches for molecular diagnosis. Metabolomics is one such powerful tool that explores comprehensibly the metabolic alternations in human diseases. It involves study of small molecules of less than 1 kD in size by either LSMS or nuclear magnetic resonance. Unlike genomics, which tells us what may have happened, metabolomics reflects what did happen. The NMR technique has an advantage of analyzing metabolites without sample preparation, thereby diminishing artifacts, is less cumbersome and with the latest database on Metabolome; about 30 000 metabolites can be identified. The study of metabolomics for several rheumatic diseases, including rheumatoid arthritis, lupus, osteoarthritis and vasculitis, has revealed distinctive metabolic signatures. Thus, metabolomics is a technique that promises precision medicine with better biomarkers, robust predictors of drug response and of disease outcome, discovery of newer metabolites and pathways in disease pathogenesis, and finally, targeted drug development. This review intends to decipher its relevance in common rheumatic diseases.
30037367 Dyslipidemia promotes germinal center reactions via IL-27. 2018 Aug Cardiovascular disease such as atherosclerosis is caused by imbalanced lipid metabolism and represents a leading cause of death worldwide. Epidemiological studies show that patients with systemic autoimmune diseases exhibit a higher incidence of atherosclerosis. Conversely, hyperlipidemia has been known to accelerate the incidence of autoimmune diseases in humans and in animal models. However, there is a considerable gap in our understanding of how atherosclerosis impacts the development of the autoimmunity in humans, and vice versa. The atherosclerosis-related autoimmune diseases include psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and diabetes mellitus. By using animal models of atherosclerosis and SLE, we have recently demonstrated that hyperlipidemia significantly accelerates the development of autoantibodies, by inducing autoimmune follicular helper T (TFH) cells. Mechanistic studies have identified that hyperlipidemia induces IL-27 production in a TLR4-dependent manner, likely via downregulating LXR expression in dendritic cells. In this case, mice lacking IL-27 do not develop enhanced antibody responses. Thus it is noted that these findings propose a mechanistic insight responsible for the tight association between cardiovascular diseases and SLE in humans. [BMB Reports 2018; 51(8): 371-372].
29686678 Immunoglobulin E-Mediated Autoimmunity. 2018 The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves' disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.