Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 29148407 | Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus sc | 2018 May | OBJECTIVES: Evaluate the presence of minor salivary gland (SG) fibrosis in primary Sjögren's syndrome (pSS) as a function of disease pathology or a consequence of ageing. METHODS: Subjects with sicca symptoms attending a Sjögren's research clinic were classified by American European Consensus Group (AECG) criteria as either pSS or non-SS (nSS). Discovery (n=34 pSS, n=28 nSS) and replication (n=35 pSS, n=31 nSS) datasets were evaluated. Minor SG cross-sections from haematoxylin and eosin stained slides were imaged, digitally reconstructed and analysed for percent area fibrosis. Relationships between SG fibrosis, age, and clinical measures were evaluated using Spearman correlations. Association with SS was assessed by: ROC curve, Variable Selection Using Random Forests (VSURF) and uni- and bi-variate regression analyses. RESULTS: SS subjects had significantly more fibrotic tissue in their minor labial salivary glands (median 24.39%, range 5.12-51.67%) than nSS participants (median 16.7%, range 5.97-38.65%, p<0.0001); age did not differ between groups (average ± SD pSS 50.2 ±13.9 years, nSS 53.8±12.4 years). In both the discovery and replication data sets, multiple regression models showed that the area of minor salivary gland fibrosis predicted pSS significantly better than age alone. Age-corrected linear regression revealed that the area of minor salivary gland fibrosis positively associated with vanBijsterveld score (p=0.042) and biopsy focus score (p=0.002). ROC curve and VSURF analyses ranked fibrosis as a significantly more important variable for subject discrimination than age. CONCLUSIONS: SG fibrosis is an element of pSS pathology that is related to focus score and is not solely attributable to age. | |
| 28710097 | Germinal centres in diagnostic labial gland biopsies of patients with primary Sjögren's s | 2017 Oct | OBJECTIVE: Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing non-Hodgkin's lymphoma (NHL), particularly parotid gland mucosa-associated lymphoid tissue (MALT) lymphomas. Presence of germinal centres (GCs) in labial gland biopsies has been suggested as predictive factor for NHL. We assessed whether presence of GCs is increased in labial gland biopsies from patients with pSS who developed parotid MALT lymphoma, the dominant NHL-subtype in pSS, compared with patients with pSS who did not develop lymphoma. METHODS: Eleven labial gland biopsies from patients with pSS that were taken prior to parotid MALT lymphoma development were compared with biopsies of 22 matched pSS controls (1:2) who did not develop lymphoma. Biopsies were evaluated for GCs (H&E and Bcl6). RESULTS: Labial gland biopsies of pSS MALT lymphoma patients, revealed GCs in 2/11 (18%) H&E sections and 3/11 (27%) Bcl6 stained sections. In controls, GCs were present in 4/22 (18%) of H&E sections and 5/22 (23%) of Bcl6 stained sections. CONCLUSION: Presence of GCs in labial gland biopsies does not differ between patients with pSS that develop parotid MALT lymphoma and patients with pSS who do not develop lymphoma. The presence of GCs in labial gland biopsies is therefore not a predictive factor for pSS-associated parotid MALT lymphomas. | |
| 28283891 | The Potential Role for Early Biomarker Testing as Part of a Modern, Multidisciplinary Appr | 2017 Apr | Sjögren's syndrome (SS) is a chronic and progressive multisystem autoimmune disease typically managed by rheumatologists. Diagnostic delays are common, due in large part to the non-specific and variable nature of SS symptoms and the slow progression of disease. The hallmark characteristics of SS are dry eye and dry mouth, but there are a broad range of other possible symptoms such as joint and muscle pain, skin rashes, chronic dry cough, vaginal dryness, extremity numbness or tingling, and disabling fatigue. Given that dry eye and dry mouth are typically the earliest presenting complaints, eye care clinicians and dental professionals are often the first point of medical contact and can provide critical collaboration with rheumatologists to facilitate both timely diagnosis and ongoing care of patients with SS. Current diagnostic criteria advocated by the American College of Rheumatology are predicated on the presence of signs/symptoms suggestive of SS along with at least two objective factors such as traditional biomarker positivity, salivary gland biopsy findings, and/or presence of keratoconjunctivitis sicca. Traditional biomarkers for SS include the autoantibodies anti-Sjögren's syndrome-related antigen A (SS-A/Ro), anti-Sjögren's syndrome-related antigen B (SS-B/La), antinuclear antibody (ANA) titers, and rheumatoid factor (RF). While diagnostically useful, these biomarkers have low specificity for SS and are not always positive, especially in early cases of SS. Several newly-identified biomarkers for SS include autoantibodies to proteins specific to the salivary and lacrimal glands [SP-1 (salivary gland protein-1), PSP (parotid secretory protein), CA-6 (carbonic anhydrase VI)]. Data suggest that these novel biomarkers may appear earlier in the course of disease and are often identified in cases that test negative to traditional biomarkers. The Sjö(®) test is a commercially available diagnostic panel that incorporates testing for traditional SS biomarkers (anti-SS-A/Ro, anti-SS-B/La, ANA, and RF), as well as three novel, proprietary early biomarkers (antibodies to SP-1, PSP, and CA-6) which provide greater sensitivity and specificity than traditional biomarker testing alone. Timely diagnosis of SS requires appropriate clinical vigilance for potential SS symptoms, referral and collaborative communication among rheumatology, ophthalmology, and oral care professions, and proactive differential work-up that includes both physical and laboratory evaluations. | |
| 27998016 | Elucidating the role of hyposalivation and autoimmunity in oral candidiasis. | 2017 Apr | INTRODUCTION: Oral candidiasis (OC) is a potential oral complication in Sjögren's syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contribute to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction, and non-salivary gland dysfunction controls (NSGD). METHODS: A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, nonparametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken. RESULTS: Data on 1526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2046 and analyzed for this study. The median whole unstimulated salivary flow rate (WUS, ml 15 min(-1) ) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR: 5.2, P < 0.001) and NSGD (3.8, IQR: 3.8, P < 0.001) but comparable with that of Sicca (1.0, IQR: 1.5, P = 0.777) participants. The median total stimulated salivary flow rate (TSS, ml 15 min(-1) ) was lowest in SS (7.0, IQR: 12.4, P < 0.001) compared to other groups. Of the 45 OC cases in this cohort, 71.1% (n = 32) were from the SS group. The prevalence of OC was highest in the SS group (4.6%, P = 0.008). SS group had twice the risk of OC than NSGD (OR = 2.2, 95%CI: 1.1-4.2, P = 0.02) and Sicca (OR = 2.2, 95% CI: 1.0-4.8, P = 0.03), adjusting for confounders; hyposalivation [WUS (OR = 5.1, 95%CI: 2.5-10.4, P < 0.001), TSS (OR = 1.9, 95%CI: 1.0-3.5, P = 0.04)], history of other autoimmune disorders (OR = 4.4, 95%CI: 1.7-11.3, P = 0.002), medications for extraglandular manifestations (OR = 2.3, 95%CI: 1.1-4.9, P = 0.03), and diabetes mellitus (4.2, 95%CI: 1.2-15.2, P = 0.02) were independent predictors of OC; females had a lower risk than males (OR = 0.29, 95%CI: 0.13-0.67, P = 0.004). Age, race, anti-SSA/SSB autoantibodies, focus score, other medications, anxiety, fatigue, cigarette smoking, alcohol, and caffeine use were not associated with oral candidiasis. CONCLUSION: Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications, i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population. | |
| 28968830 | Antibodies to aquaporins are frequent in patients with primary Sjögren's syndrome. | 2017 Dec 1 | OBJECTIVES: Several aquaporins (AQPs) are present in the salivary glands, likely contributing to their secretions. AQP dysfunction may contribute to the salivary gland dysfunction in SS. Antibodies to AQP4 and AQP1 are detected in neuromyelitis optica and are believed to play a pathogenic role. We aimed to search for antibodies to several AQPs in the sera from SS patients in an effort to shed light on the pathogenic mechanisms of SS. METHODS: We searched for antibodies to six AQPs in the sera of 34 SS patients without neurological findings using ELISAs with synthetic peptides corresponding to the three extracellular domains of each AQP, radioimmunoassays with AQPs, Western blots and competition experiments with cell-embedded AQPs. RESULTS: Thirteen (38.2%) SS patients had antibodies to extracellular domains of AQP1 (two), AQP3 (one), AQP8 (six) or AQP9 (four); none had AQP4 or AQP5 antibodies. Each patient had antibodies to only one extracellular domain. AQP binding was further verified by radioimmunoassay with intact AQPs, western blots and AQP-transfected cells. In contrast, none of the 106 healthy controls or 68 patients with other autoimmune diseases had antibodies to intact AQPs. Expression of AQP8 (the major antibody target) on human salivary glands was shown by immunohistochemistry. Patients with anti-AQP antibodies had more severe xeropthalmia compared with anti-AQP-negative patients, suggesting a potential pathogenic role of these antibodies. CONCLUSION: Antibodies to AQPs (especially to AQP8 and AQP9) are frequent in SS patients. The likely important role of AQPs in salivary gland secretions justifies further research. | |
| 29088284 | A qualitative exploration of physical, mental and ocular fatigue in patients with primary | 2017 | INTRODUCTION: Primary Sjögren's Syndrome (pSS) affects exocrine glands such as those producing the tear film, leading to dry and painful eyes, but is also associated with fatigue. The experience of fatigue in pSS, and its relationship with sicca symptoms, is poorly understood. METHODS: Twenty people diagnosed with pSS were recruited to participate in a semi-structured qualitative interview about their symptoms experience. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: People with pSS described physical tiredness, mental fatigue and ocular fatigue. Mental fatigue was characterised by difficulties in attention, particularly, the ability to follow conversations and short-term memory problems. Participants linked their experience of fatigue to feeling of depression, frustration, irritation and anxiety, and therefore, fatigue was suggested to have had a large impact on their psychological well-being. People with pSS also described a range of ocular symptoms including pain, dryness, and itching, which were compounded by fatigue. For some, eye fatigue was pervasive, and daily activities involving the eyes such as reading, using the computer and driving were impaired. In some cases, the level of ocular discomfort was so severe it prevented sleep, which in turn impacted on general fatigue levels. CONCLUSIONS: People with pSS experience fatigue in a range of ways; physical, mental and ocular fatigue were described. Fatigue was suggested to exacerbate other ocular symptoms, posed serious physical limitations and caused psychological distress. Further research into the nature of fatigue and ocular symptoms in pSS is required. | |
| 28964279 | Pediatric primary Sjögren syndrome presenting with bilateral ranulas: A case report and s | 2017 Oct | CONTEXT: Primary Sjögren syndrome is uncommon in children, and the standard clinical criteria used in diagnosis of adult Sjögren syndrome will miss many children with the disease. Floor of mouth ranulas have not been described in Sjögren syndrome. OBJECTIVE: This study aims to describe a novel presentation of juvenile primary Sjögren syndrome, and to present a comprehensive systematic review of the literature regarding the presentation and diagnosis of Sjögren syndrome in children. DATA SOURCES: Ovid MEDLINE. STUDY SELECTION: A MEDLINE literature search was performed using the following search terms: primary, Sjögren, disease, and children. Results were limited to human subjects and articles written in English between 1981 and 2014. Applicable articles were reviewed and qualitatively summarized. DATA EXTRACTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRIMA). RESULTS: Initial MEDLINE search yielded 146 articles, 80 of which were excluded as not clinically pertaining to Sjögren syndrome. An additional 25 were excluded due to lack of pediatric-specific data. Systematic review of the literature revealed no reports of ranula in association with Sjögren syndrome. 6 papers were manually included from review of reference lists of included articles. Our review indicated that recurrent parotitis is the most commonly reported presenting symptom in children, followed by ocular and oral symptoms, musculoskeletal, and renal symptoms. Compared to adults, children are less likely to present with dry eyes and mouth. LIMITATIONS: All studies were retrospective chart reviews, case series or case reports. CONCLUSION: This is the first report of a child presenting with floor of mouth ranulas in association with Sjögren syndrome. While recurrent parotitis is the most common presentation in children, other salivary gland and extra-salivary manifestations may be seen, and the clinician must maintain a high index of suspicion for underlying Sjögren syndrome. | |
| 28516978 | Sialendoscopic management of autoimmune sialadenitis: a review of literature. | 2017 Apr | Autoimmune diseases of major salivary glands include Sjögren's syndrome and a complex of disorders classified as immunoglobulin G4-related diseases. These pathologies are characterised by an autoimmune reaction mediated by T-helper lymphocytes that targets the ducts of exocrine glands in Sjögren's syndrome and glandular parenchyma in immunoglobulin G4-related diseases. Immunoglobulin G4-related diseases represent recently introduced multi-organ diseases that also involve the salivary glands. However, the morbid conditions once known as Mikulicz's disease and Kuttner's tumour were recently considered as two variants of immunoglobulin G4-related diseases affecting the major salivary glands ( immunoglobulin G4-related sialadenitis). This review briefly summarises the pathogenesis and clinical features of autoimmune diseases of the major salivary glands, focusing on the diagnostic and therapeutic role of sialendoscopy. | |
| 28355737 | [Clinical features and prognostic analysis of neuromyelitisoptica spectrum disease with sj | 2017 Mar 21 | Objective: To explore the clinical features and conduct prognostic analysis about visual recovery and relapse of neuromyelitisoptica (NMO) spectrum disease (NMOSD) with sjogren syndrome (SS). Methods: A retrospective and prospective observational study was conducted.Between July 2013 and June 2016, 172 patients with NMOSD (NMOSD-non SS: 116/172, 67.4%; NMOSD-SS: 56/172, 32.6%) were assessed at Beijing Tongren Hospital, Capital Medical University, Beijing, China.The prognostic factors of NMOSD-SS patients were also analyzed. Results: As compared with NMOSD-non SS patients, NMOSD-SS patients had worse visual impairment (percentage of patients with visual acuity less than 0.1, 83.9% vs 69.8%, P<0.05), higher positive rate of SSA (92.9% vs 0.0%, P<0.05), higher proportion of dryness of mouth and eye (66.1% vs 5.2%, P<0.05) as well as higher percentage of reduced visual evoked potential (VEP) amplitude (60.7% vs 43.1%, P<0.05). NMOSD-SS patients had a significantly higher average year recurrent frequency (0.58 vs 0.53) and significantly shorter mean recurrence time (6.7 months vs 12.4 months, P<0.05). The results showed that recurrent eyes, the worst visual acuities of onset less than 0.1 were independent risk factors of visual impairment (visual activity <0.1), according to at least six months' follow-up of all NMOSD-SS patients (OR=6.410 and 9.434, respectively, P<0.05). Meanwhile, immunosuppressive drugs were protective factors of relapse in NMOSD-SS patients (OR=0.107, P<0.05). Conclusions: NMOSD-SS patients have worse visual impairment, and they are more vulnerable to relapse than NMOSD-non SS patients, and the vision is lack of recovery for NMOSD-SS with recurrent eyes or the worst vision of onset less than 0.1.Immunosuppressive drugs can reduce the recurrence of NMOSD-SS relapse. | |
| 28837372 | Update upon efficacy and safety of etanercept for the treatment of spondyloarthritis and j | 2018 May | TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis (AS), psoriasis (Ps) and/or psoriatic arthritis (PsA) and may be administered off-label to treat disseminated granuloma annulare, systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this article, we discuss the efficacy and safety of etanercept in the treatment of spondyloarthritis and juvenile idiopathic arthritis (JIA). Etanercept is effective in the treatment of PsA, AS, JIA and uveitis. Independent predictors of achieving a sustained clinical improvement or MDA in children with JIA include shorter disease duration, no concurrent oral corticosteroid use, history of chronic anterior uveitis and age <9 years. IBD incidence was lower in patients receiving etanercept plus MTX. Intra-articular administration of etanercept seems to favor a prompt target joint improvement without serious adverse events. Etanercept improve endothelial function reducing the risk of acute cardiovascular and/or cerebrovascular events. The most commonly reported adverse events were nasopharyngitis, epidermal and dermal conditions, upper respiratory tract infection, cough, headache and fatigue. | |
| 27334257 | Maternal outcomes and follow-up of preterm and term neonates born to mothers with systemic | 2018 Jan | OBJECTIVE: There is little follow-up data in preterm infants from mothers with systemic lupus erythematosus (SLE). The aim of this study was to determine maternal outcomes and compare neonatal outcomes in preterm and term infants born to mothers with SLE. METHODS: This study is a prospective study in a tertiary medical care center and clinical research center for rheumatoid arthritis. Demographic data, clinical features, laboratory findings, treatment and complications in 77 pregnant SLE patients were prospectively evaluated from 2007 to 2013. RESULTS: Ninety-two infants (44 males and 48 females including four sets of twins) from 77 mothers with SLE were enrolled. Multivariate logistic analysis indicated that flares were significantly associated with antiphospholipid antibodies of lupus anticoagulant during pregnancy (p = 0.009) and preterm birth (p = 0.017). Compared with term infants, preterm infants had significantly higher antinuclear antibodies (ANA) positivity (p = 0.001) at 12 months of age in multivariate logistic analysis. CONCLUSION: Preterm birth is associated with maternal flares and persistent ANA positivity at 12 months of life in infants born to mothers with SLE. | |
| 29039280 | Very long-chain n-3 fatty acids and human health: fact, fiction and the future. | 2018 Feb | EPA and DHA appear to be the most important n-3 fatty acids, but roles for n-3 docosapentaenoic acid are now also emerging. Intakes of EPA and DHA are usually low, typically below those recommended. Increased intakes result in higher concentrations of EPA and DHA in blood lipids, cells and tissues. Increased content of EPA and DHA modifies the structure of cell membranes and the function of membrane proteins. EPA and DHA modulate the production of lipid mediators and through effects on cell signalling can alter the patterns of gene expression. Through these mechanisms, EPA and DHA alter cell and tissue responsiveness in a way that often results in more optimal conditions for growth, development and maintenance of health. DHA has vital roles in brain and eye development and function. EPA and DHA have a wide range of physiological roles, which are linked to certain health or clinical benefits, particularly related to CVD, cancer, inflammation and neurocognitive function. The benefits of EPA and DHA are evident throughout the life course. Future research will include better identification of the determinants of variation of responses to increased intake of EPA and DHA; more in-depth dose-response studies of the effects of EPA and DHA; clearer identification of the specific roles of EPA, docosapentaenoic acid and DHA; testing strategies to enhance delivery of n-3 fatty acids to the bloodstream; and exploration of sustainable alternatives to fish-derived very long-chain n-3 fatty acids. | |
| 28739356 | Development of autoantibodies precedes clinical manifestations of autoimmune diseases: A c | 2017 Sep | The etiology of autoimmune diseases is due to a combination of genetic predisposition and environmental factors that alter the expression of immune regulatory genes through various mechanisms including epigenetics. Both humoral and cellular elements of the adaptive immune system play a role in the pathogenesis of autoimmune diseases and the presence of autoantibodies have been detected in most but not all autoimmune diseases before the appearance of clinical symptoms. In some cases, the presence or levels of these autoantibodies portends not only the risk of developing a corresponding autoimmune disease, but occasionally the severity as well. This observation is intriguing because it suggests that we can, to some degree, predict who may or may not develop autoimmune diseases. However, the role of autoantibodies in the pathogenesis of autoimmune diseases, whether they actually affect disease progression or are merely an epiphenomenon is still not completely clear in many autoimmune diseases. Because of these gaps in our knowledge, the ability to accurately predict a future autoimmune disease can only be considered a relative risk factor. Importantly, it raises the critical question of defining other events that may drive a patient from a preclinical to a clinical phase of disease. | |
| 28210620 | Association of PTPN22 Haplotypes (-1123G>C/+1858C>T) with Rheumatoid Arthritis in Western | 2017 | Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP), a consequence of the breakdown of immune tolerance. The lymphoid tyrosine phosphatase (Lyp) protein has significant effects on maintenance of peripheral immune tolerance. Two polymorphic variants (-1123G>C and +1858C>T) at PTPN22 gene that encodes this protein have been associated with autoimmune disorders and found in strong linkage disequilibrium in Caucasian population. We evaluated whether PTPN22 haplotypes (-1123G>C/+1858C>T) are associated with anti-CCP antibodies, as well as susceptibility to RA in a Western Mexican population. A total of 315 RA patients and 315 control subjects (CS) were included. The polymorphisms were genotyped by PCR-RFLP and the anti-CCP antibodies were determined by ELISA. The PTPN22 polymorphisms were in strong linkage disequilibrium (D' = 1.00 in CS). The susceptibility haplotype CT was significantly more frequent in RA patients than in CS (OR 2.18, 95% CI 1.15-4.16, p = 0.01). No association between haplotypes and anti-CCP antibodies levels was observed. In conclusion, this study confirmed that -1123G>C and +1858C>T PTPN22 polymorphisms are in strong linkage disequilibrium and the CT haplotype is a susceptibility marker to RA in Western Mexico. However, the PTPN22 haplotypes are not associated with anti-CCP antibodies. | |
| 27974099 | TNF inhibitors increase fat mass in inflammatory rheumatic disease: a systematic review wi | 2017 Mar | OBJECTIVES: To assess body composition of patients with inflammatory rheumatic disease and the effect of TNF inhibitors on it. METHODS: This was systematic review with meta-analysis of studies consulted on PubMed, Cochrane Library and EMBASE and assessing body composition in patients with rheumatoid arthritis or spondyloarthritis. We compared i) patients with healthy controls and ii) body components before and after TNF inhibitors. RESULTS: Among the 703 articles reviewed, 19 met the inclusion criteria. In patients with rheumatoid arthritis, a significant increase in fat mass (+1.85 kg, p=0.02), adiposity (+3.53%, p<0.00001) and android mass (+1.7 kg, p<0.00001) and a significant decrease in lean mass (-3.03 kg, p=0.01), were observed. In patients with spondyloarthritis, a significant but modest increase in fat mass (+0.69 kg, p=0.03) and a significant decrease in lean mass (-3.74 kg, p=0.03) were observed. Nine studies assessed impact of TNF inhibitors on body composition, with an increase of fat mass in the short and long term in all studies. Data on lean mass were controversial. Two studies found an increase in visceral or android mass under TNF inhibitors. CONCLUSIONS: Patients with inflammatory rheumatic disease have a significant decrease in lean mass and increase in fat mass. The use of TNF inhibitors is associated with a further increase in fat mass including android fat, which could potentially have cardiovascular consequences. | |
| 28814359 | The risk of autoimmune connective tissue diseases in patients with atopy: A nationwide pop | 2017 Sep 1 | BACKGROUND: The relationship between autoimmune connective tissue disease (ACTD) and atopy is controversial. OBJECTIVES: To investigate the risks of ACTDs in patients with atopic triad diseases, including atopic dermatitis, allergic rhinitis, and asthma, by using a nationwide data base. METHODS: A cohort of 155,311 patients newly diagnosed with atopic dermatitis, allergic rhinitis, or asthma in 2002-2011 was obtained from the Taiwan National Health Insurance Research Database. An age- and sex-matched control group was selected from the same data base. The association between atopy and ACTD was investigated by using Cox proportional hazards regression analyses. RESULTS: Atopic dermatitis, allergic rhinitis, and asthma were present in 12.1, 78.6, and 26.3%, respectively, of the patients with atopy. The presence of atopic diseases increased the overall risk of ACTDs (incidence rate ratio 1.85 [95% confidence interval {CI}, 1.52-2.25]). The hazard ratio (HR) for ACTDs remained higher after adjusting for age, sex, urbanization level, socioeconomic status, and comorbidities. Individual risks of systemic lupus erythematosus (HR 1.58 [95% CI, 1.06-2.37]), rheumatoid arthritis (HR 1.74 [95% CI, 1.31-2.33]), and Sjögren syndrome (HR 2.49 [95% CI, 1.71-3.63]) were also higher. The coexistence of atopic triad diseases increased the risk of ACTDs from 1.80 (95% CI, 1.48-2.21) for one atopic disease to 3.29 (95% CI, 1.22-8.88) for three atopic diseases. CONCLUSION: The presence of atopic triad diseases is significantly associated with risks of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome, and their coexistence exacerbates this risk. To our knowledge, this was the first study that reported an increased risk of Sjögren syndrome among patients with atopy. | |
| 28716457 | Interleukin-32 in chronic inflammatory conditions is associated with a higher risk of card | 2017 Sep | Cardiovascular diseases (CVD) are the most frequent cause of death in developed countries. Their prevalence is higher in several chronic inflammatory conditions. This is likely due to the substantial contribution of the inflammatory status of the patients to the development and stability of atherosclerotic plaques. Recent evidence suggests that interleukin (IL)-32 may be involved in the conditions that contribute to CVD. IL-32 not only modulates important inflammatory pathways known to contribute to the pathogenesis of both inflammatory diseases and atherosclerosis, including tumor necrosis factor (TNF)α, IL-6 or IL-1β, but it has been also suggested to modulate endothelial cell function and the serum concentration of high-density lipoprotein (HDL). In this review, we highlight the recent advances in the field of IL-32 in relation to chronic inflammatory disorders and argue for a role of IL-32 in the increased prevalence of CVD in these patients. | |
| 28155935 | Folate binding protein: therapeutic natural nanotechnology for folic acid, methotrexate, a | 2017 Feb 16 | Blood serum proteins play a critical role in the transport, biodistribution, and efficacy of systemically-delivered therapeutics. Here, we have investigated the concentration- and ligand-dependent aggregation of folate binding protein (FBP), focusing in particular on folic acid, an important vitamin and targeting agent; methotrexate, an antifolate drug used to treat cancer and rheumatoid arthritis; and leucovorin which is used to decrease methotrexate toxicity. We employed atomic force microscopy to characterize, on a particle-by-particle basis, the volumes of the FBP nanoparticles that form upon ligand binding. We measured the distribution of FBP nanoparticle volumes as a function of ligand concentration over physiologically- and therapeutically-relevant ranges. At physiologically-relevant concentrations, significant differences in particle volume distributions exist that we hypothesize are consistent with different trafficking mechanisms for folic acid and methotrexate. In addition, we hypothesize leucovorin is trafficked and delivered like folic acid at therapeutically-relevant concentrations. We propose that changes in dosing procedures could improve the delivery and therapeutic index for methotrexate and other folic acid-targeted drug conjugates and imaging agents. Specifically, we suggest pre-binding the drugs to FBP may provide a better formulation for drug delivery of methotrexate for both cancer and rheumatoid arthritis. This would be analogous to pre-binding paclitaxel to albumin, which is already used in the clinic. | |
| 25964045 | Anti-inflammatory activity of green versus black tea aqueous extract in a rat model of hum | 2017 Feb | AIM: Recently, there has been an increasing interest in tea (Camellia sinensis) as a protective agent against inflammatory diseases. Here, we evaluated/compared the anti-inflammatory activity of two different doses (0.5 and 1.0 g/kg body weight) of green tea aqueous extract (GTE, rich in catechins) and black tea aqueous extract (BTE, rich in theaflavins and thearubigins) in rat adjuvant-induced arthritis (AIA). METHODS: Adjuvant-induced arthritis rat model received orally/daily distilled water as vehicle, indomethacin (1.0 mg/kg body weight; a non-steroidal/anti-inflammatory drug), or tea aqueous extracts (for 28 or 14 consecutive days starting from day 0 or 14 of arthritis induction, respectively). RESULTS: The present study showed that only the high dose of GTE (from day 0) significantly alleviated (P < 0.05-0.001) all complications shown in arthritic rats, including synovial joint inflammation, elevation in erythrocyte sedimentation rate, blood leukocytosis (due to lymphocytosis and neutrocytosis), and changes in weight/cellularity of lymphoid organs. The anti-arthritic activity of the high dose of GTE (from day 0) was comparable (P > 0.05) with that of indomethacin (12.9-53.8 vs. 9.5-48.4%, respectively) and mediated by significantly decreasing and down-regulating (P < 0.001) the systemic production of pro-inflammatory cytokines and the expression of chemokine receptor-5 in synovial tissues, respectively. Moreover, the anti-arthritic activity of tea aqueous extracts was in the following order: high dose of GTE > low dose of GTE ≥ high dose of BTE > low dose of BTE. CONCLUSION: The present study proved the anti-inflammatory activity of GTE over BTE and equal to that of indomethacin in AIA rat model. | |
| 29390349 | Sjögren's syndrome manifesting as clinicopathological features of TAFRO syndrome: A case | 2017 Dec | RATIONALE: TAFRO syndrome is a newly proposed disorder that manifests as thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. In this report, we describe the development of severe TAFRO syndrome-like systemic symptoms during the clinical course of juvenile-onset Sjögren's syndrome in a 32-year-old woman. PATIENT CONCERNS: The patient was admitted due to dyspnea, fever, polyarthralgia, and generalized edema. She had been diagnosed with Sjögren's syndrome at the age of 14 years, based on histopathological examination of a biopsy of the minor salivary glands and the development of Raynaud's phenomenon, with no follow-up treatment required. On admission, she presented with anemia, elevated C-reactive protein levels, anasarca, and hepato-splenomegaly. A bone marrow examination revealed increased megakaryocytes with reticulin fibrosis, and the histopathology of an axillary lymph node was consistent with mixed-type Castleman disease. Eventually, she developed thrombocytopenia. INTERVENTIONS: Her symptoms fulfilled all of the major and minor categories of the diagnostic criteria for TAFRO syndrome. However, considering her prior diagnosis, we assumed that the clinical presentation was consistent with an acute exacerbation of Sjögren's syndrome. Unlike typical cases of TAFRO syndrome, the administration of relatively low-dose prednisolone relieved her symptoms. LESSONS: Differentiation between TAFRO syndrome and exacerbation of an autoimmune disease is clinically important, although this can be challenging. Identification of specific biomarkers for TAFRO syndrome would be clinically beneficial. |