Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27416759 Effective suppression of C5a-induced proinflammatory response using anti-human C5a repebod 2016 Sep 2 The strongest anaphylatoxin, C5a, plays a critical role in the proinflammatory responses, causing the pathogenesis of a number of inflammatory diseases including sepsis, asthma, and rheumatoid arthritis. Inhibitors of C5a thus have great potential as therapeutics for various inflammatory disorders. Herein, we present the development of a high-affinity repebody against human C5a (hC5a), which effectively suppresses the proinflammatory response. A repebody scaffold composed of leucine-rich repeat (LRR) modules was previously developed as an alternative protein scaffold. A repebody specifically binding to hC5a was selected through a phage display, and its affinity was increased up to 5 nM using modular engineering. The repebody was shown to effectively inhibit the production of C5a-induced proinflammatory cytokines by human monocytes. To obtain insight into a mode of action by the repebody, we determined its crystal structure in complex with hC5a. A structural analysis revealed that the repebody binds to the D1 and D3 regions of hC5a, overlapping several epitope residues with the hC5a receptor (hC5aR). It is thus likely that the repebody suppresses the hC5a-mediated immune response in monocytes by blocking the binding of hC5a to its receptor. The anti-hC5a repebody can be developed as a potential therapeutic for C5a-involved inflammatory diseases.
27337048 Constrained Cyclic Peptides as Immunomodulatory Inhibitors of the CD2:CD58 Protein-Protein 2016 Aug 19 The interaction between the cell-cell adhesion proteins CD2 and CD58 plays a crucial role in lymphocyte recruitment to inflammatory sites, and inhibitors of this interaction have potential as immunomodulatory drugs in autoimmune diseases. Peptides from the CD2 adhesion domain were designed to inhibit CD2:CD58 interactions. To improve the stability of the peptides, β-sheet epitopes from the CD2 region implicated in CD58 recognition were grafted into the cyclic peptide frameworks of sunflower trypsin inhibitor and rhesus theta defensin. The designed multicyclic peptides were evaluated for their ability to modulate cell-cell interactions in three different cell adhesion assays, with one candidate, SFTI-a, showing potent activity in the nanomolar range (IC50: 51 nM). This peptide also suppresses the immune responses in T cells obtained from mice that exhibit the autoimmune disease rheumatoid arthritis. SFTI-a was resistant to thermal denaturation, as judged by circular dichroism spectroscopy and mass spectrometry, and had a half-life of ∼24 h in human serum. Binding of this peptide to CD58 was predicted by molecular docking studies and experimentally confirmed by surface plasmon resonance experiments. Our results suggest that cyclic peptides from natural sources are promising scaffolds for modulating protein-protein interactions that are typically difficult to target with small-molecule compounds.
27309544 The correlation between miR-200c and the severity of interstitial lung disease associated 2017 Mar OBJECTIVES: To explore the correlation between microRNA (miR)-200c and the severity of interstitial lung disease (ILD) associated with connective tissue diseases (CTDs). METHOD: We recruited 218 patients with CTDs who were evaluated with high-resolution computed tomography (HRCT) and the pulmonary function test (PFT). Peripheral blood mononuclear cells (PBMCs) were acquired from 23 patients with systemic sclerosis (SSc), 29 with dermatomyositis/polymyositis (DM/PM), 30 with primary Sjögren's syndrome (pSS), 47 with rheumatoid arthritis (RA), and 23 normal controls to detect the expression level of miR-200c by quantitative reverse transcription polymerase chain reaction (QRT-PCR). miR-200c levels were compared among the different disease groups, between the group with ILD (CTD+ILD) and the group without ILD (CTD-ILD), and between mild and severe ILD groups. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were compared among the different CTD groups and the different CTD+ILD groups. RESULTS: The miR-200c level in the SSc group was significantly higher than in the DM/PM, pSS, and RA groups, and the levels in the DM/PM and pSS groups were significantly higher than in the RA group. The level of miR-200c in the CTD+ILD group was significantly higher than in the CTD-ILD group, and the level in the severe ILD group was significantly higher than in the mild ILD group. FVC and FEV1 were significantly different among the different CTD groups, and among the different CTD+ILD groups. There was a negative correlation between the level of miR-200c and FVC and FEV1. CONCLUSIONS: The level of miR-200c was positively correlated with the severity of ILD, and miR-200c in PBMCs could be a biomarker of the severity of ILD in CTDs.
27211841 Sinomenine attenuates renal fibrosis through Nrf2-mediated inhibition of oxidative stress 2016 Aug 1 Renal fibrosis is the common feature of chronic kidney disease and mainly mediated by TGFβ-associated pro-fibrogenic signaling, which causes excessive extracellular matrix accumulation and successive loss of kidney functions. Sinomenine (SIN), an alkaloid derived from medicinal herb extensively used in treatment of rheumatoid arthritis and various inflammatory disorders, displays renal protective properties in experimental animals; however its pharmacological potency against renal fibrosis is not explored. In this study we report that SIN possesses strong anti-renal fibrosis functions in kidney cell and in mouse fibrotic kidney. SIN beneficially modulated the pro-fibrogenic protein expression in TGFβ-treated kidney cells and attenuated the renal fibrotic pathogenesis incurred by unilateral ureteral obstruction (UUO), which correlated with its activation of Nrf2 signaling - the key defender against oxidative stress with anti-fibrotic potentials. Further investigation on its regulation of Nrf2 downstream events revealed that SIN significantly balanced oxidative stress via improving the expression and activity of anti-oxidant and detoxifying enzymes, and interrupted the pro-fibrogenic signaling of TGFβ/Smad and Wnt/β-catenin. Even more impressively SIN achieved its anti-fibrotic activities in an Nrf2-dependent manner, suggesting that SIN regulation of Nrf2-associated anti-fibrotic activities constitutes a critical component of SIN's renoprotective functions. Collectively our studies have demonstrated a novel anti-fibrotic property of SIN and its upstream events and provided a molecular basis for SIN's potential applications in treatment of renal fibrosis-associated kidney disorders.
27092422 Development of an interleukin (IL)-33 sandwich ELISA kit specific for mature IL-33. 2016 Interleukin (IL)-33 is an inflammatory cytokine and belongs to the IL-1 family of cytokines. There are eleven members of the IL-1 family of cytokines and all have important roles in host defense against infections. Their levels are increased during infection and in various auto-inflammatory diseases. IL-33 is also associated with autoimmune diseases such as asthma, atopic dermatitis, rheumatoid arthritis, and atherosclerosis. IL-33 receptors consist of IL-1R4 and IL-1R3 to induce both Th1 and Th2 type immune response. Here we present the development of monoclonal antibodies (mAbs) against human mature IL-33. Recombinant human mature IL-33 protein was expressed in E. coli and purified by multi-step affinity chromatography. The human IL-33 activity was examined in HMC-1 and Raw 264.7 cells. Mice were immunized with the biologically active mature IL-33 to generate mAb against IL-33. The anti-IL-33 mAb (clone/4) was used as a capture antibody for a sandwich enzyme-linked immunosorbent assay (ELISA). This assay detects mature IL-33 with a high sensitivity (80 pg/mL) but does not recognize the biologically inactive precursor IL-33. This article describes the methods for a newly developed IL-33 ELISA kit that is specific for mature IL-33 and may be used to analyze bioactive mature IL-33 in various immunological diseases.
27035226 Inhibition of RANKL-induced osteoclast differentiation through the downregulation of c-Fos 2016 May Osteoclasts, derived from hematopoietic stem cells, are specialized macrophages and have a homeostatic role in skeletal modeling and remodeling with bone-forming osteoblasts. However, excessive osteoclast activity induces bone diseases, including osteoporosis, periodontitis and rheumatoid arthritis. Natural substances have received attention as therapeutic drugs in human diseases. In the current study, cells isolated from mouse bone marrow, and a mouse model, were used to determine the effect of centipedegrass extract (CGE) on osteoclasts. Multiple concentrations of CGE were administered to bone marrow cells for 24‑72 hours and, for the in vivo study, mice were treated with CGE for 8 days. The effects of CGE on transcription and translation of osteoclast-associated molecules were then determined using reverse transcription-polymerase chain reaction and immunoblotting, respectively. In the present study it was shown that CGE extracted from Eremochloa ophiuroides (centipedegrass) inhibited receptor activator of nuclear factor κ‑B ligand (RANKL)‑mediated osteoclast differentiation in bone marrow macrophages, without cytotoxicity, in a dose‑dependent manner. CGE decreased the expression levels of osteoclast‑specific genes, including matrix metalloproteinase‑9, osteoclast‑associated immunoglobulin‑like receptor and cathepsin K, however, CGE had no inhibitory effect on the expression levels of mitogen‑activated protein kinases, nuclear factor‑κB and Akt. Furthermore, the protein and RNA levels of RANKL‑induced c‑Fos and nuclear factor of activated T-cell cytoplasmic 1 were suppressed by CGE. These results indicated that CGE may serve as a useful drug in the prevention of bone loss.
26923308 Reverse shoulder arthroplasty with a cementless short metaphyseal humeral implant without 2016 Aug BACKGROUND: Reverse shoulder prostheses are increasingly used in recent years for treatment of glenohumeral arthropathy with deficient rotator cuff. Bone preservation is becoming a major goal in shoulder replacement surgery. Metaphyseal humeral components without a stem were developed to minimize bone resection and preserve bone. This study evaluated the clinical and radiologic outcomes at 2 to 7 years using a novel short metaphyseal reverse total shoulder arthroplasty (rTSA) prosthesis without a diaphyseal stem. METHODS: Between 2005 and 2010, 102 consecutive patients underwent rTSA with this implant, and 98 (20 men, 78 women) were available for follow-up. Mean age was 74.4 years (range, 38-93 years). Indications were cuff tear arthropathy, 65; fracture sequelae, 12; rheumatoid arthritis, 13; failed rotator cuff repair, 3; cuff deficiency with loosening of anatomic prosthesis, 3; and acute trauma, 2; with 17 of these as revisions. RESULTS: Patients' satisfaction (Subjective Shoulder Value) improved from 8 of 100 to 85 of 100. The Constant score improved from 14 to 59 (age- and sex-adjusted, 86; P < .0001). Range of motion improved from 47° to 129° in elevation, 10° to 51° in external rotation, and 21° to 65° in internal rotation. Radiographic analysis showed no lucencies, subsidence, or stress shielding around the humeral or glenoid components. Glenoid notching was found in 21 patients (18 grade 1-2; 3 grade 3). CONCLUSIONS: The short metaphyseal rTSA design without a diaphyseal stem shows encouraging short- to midterm results, with excellent pain relief and shoulder function, restoration of good active range of motion, and high patient satisfaction scores. The design of this implant seems to result in improved rotational movements, low incidence of glenoid notching, and no implant loosening, subsidence, or stress shielding.
26909742 Methotrexate and its therapeutic antagonists caffeine and theophylline, target a motogenic 2016 May Methotrexate (MTX) is a widely used treatment for inflammatory diseases such as rheumatoid arthritis and psoriasis, based on the concept that it is immunosuppressive. Its mechanism of action, however, remains unclear, although it is thought to depend on adenosine. Caffeine and theophylline, which have several targets including adenosine receptors, have been shown to suppress the beneficial clinical effects of MTX. Here we show that MTX and caffeine and theophylline differentially affect a motogenic T-cell mechanism driven by endogenous thrombospondin-1 (TSP-1) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1). MTX stimulated TSP-1 expression and the motogenic TSP-1/TSP-1 receptor mechanism in primary human T cells, hence mimicking IL-2 and CXCL12, which similar to MTX, dampen inflammatory disease. SiRNA-mediated gene silencing of TSP-1 and LRP1 inhibited this stimulatory effect. Caffeine and theophylline inhibited the TSP-1/TSP-1 receptor mechanism by inhibiting LRP1 expression. These results indicate that the effect of MTX on T cells is immunoregulatory rather than immunosuppressive, and suggest a pathway dependent on TSP-1/TSP-1 receptor interactions for the regulation of immune responses.
26884610 Methods for measuring myeloperoxidase activity toward assessing inhibitor efficacy in livi 2016 Apr Myeloperoxidase aids in clearance of microbes by generation of peroxidase-mediated oxidants that kill leukocyte-engulfed pathogens. In this review, we will examine 1) strategies for in vitro evaluation of myeloperoxidase function and its inhibition, 2) ways to monitor generation of certain oxidant species during inflammation, and 3) how these methods can be used to approximate the total polymorphonuclear neutrophil chemotaxis following insult. Several optical imaging probes are designed to target reactive oxygen and nitrogen species during polymorphonuclear neutrophil inflammatory burst following injury. Here, we review the following 1) the broad effect of myeloperoxidase on normal physiology, 2) the difference between myeloperoxidase and other peroxidases, 3) the current optical probes available for use as surrogates for direct measures of myeloperoxidase-derived oxidants, and 4) the range of preclinical options for imaging myeloperoxidase accumulation at sites of inflammation in mice. We also stress the advantages and drawbacks of each of these methods, the pharmacokinetic considerations that may limit probe use to strictly cell cultures for some reactive oxygen and nitrogen species, rather than in vivo utility as indicators of myeloperoxidase function. Taken together, our review should shed light on the fundamental rational behind these techniques for measuring myeloperoxidase activity and polymorphonuclear neutrophil response after injury toward developing safe myeloperoxidase inhibitors as potential therapy for chronic obstructive pulmonary disease and rheumatoid arthritis.
26773186 Fecal calprotectin is associated with disease activity in patients with ankylosing spondyl 2016 Jan 1 Calprotectin is one of the major antimicrobial S100 leucocyte proteins. Serum calprotectin levels are associated with certain inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease. The aim of this study was to investigate serum and fecal calprotectin levels in patients with ankylosing spondylitis (AS) and show their potential relations to the clinical findings of the disease. Fifty-one patients fulfilling the New York criteria of AS and 43 healthy age- and gender-matched volunteers were included in the study. Physical and locomotor system examinations were performed and history data were obtained for all patients. Disease activity parameters were assessed together with anthropometric parameters. Routine laboratory examinations and genetic testing (HLA-B27) were performed. Serum calprotectin levels and fecal calprotectin levels were measured by an enzyme-linked immunosorbent assay. The mean age of the patients was 41.5 years, the mean duration of the disease was 8.6 years, and the delay in diagnosis was 4.2 years. Serum calprotectin levels were similar in both AS patients and in the control group (p=0.233). Serum calprotectin level was correlated with Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI) (p=0.001, p=0.002, respectively). A higher level of fecal calprotectin was detected in AS patients when compared with the control group. A statistically significant correlation between fecal calprotectin level and BASDAI, BASFI, C-reactive protein and Erythrocyte sedimentation rate were detected (p=0.002, p=0.005, p=0.001, p=0.002, respectively). The results indicated that fecal calprotectin levels were associated with AS disease findings and activity parameters. Calprotectin is a vital disease activity biomarker for AS and may have an important role in the pathogenesis of the disease. Multi-centered prospective studies are needed in order to provide further insight.
26483318 State-of-the-Art Imaging of the Lung for Connective Tissue Disease (CTD). 2015 Dec Involvement of the respiratory system is common in connective tissue diseases (CTDs), and the resultant lung injury can affect every part of the lung: the pleura, alveoli, interstitium, vasculature, lymphatic tissue, and large and/or small airways. Most of the parenchymal manifestations of CTD are similar to those found in interstitial lung diseases (ILDs), especially idiopathic interstitial pneumonias, and can be classified using the same system. Although there is some overlap, each CTD is associated with a characteristic pattern of pulmonary involvement. For this reason, thin-section CT as well as pulmonary function tests and serum markers are utilized for diagnosis, disease severity assessment, and therapeutic efficacy evaluation of ILD associated with CTD. In addition, newly developed pulmonary magnetic resonance imaging (MRI) procedures have been recommended as useful alternative imaging options for patients with CTD. This review article will (1) address radiological findings for chest radiography and conventional or thin-section CT currently used for six major types of CTD, rheumatoid arthritis, scleroderma (progressive systemic sclerosis), polymyositis/dermatomyositis, systemic lupus erythematosus, Sjögren syndrome and mixed connective tissue disease; (2) briefly deal with radiation dose reduction for thin-section CT examination; and (3) discuss clinically applicable or state-of-the-art MR imaging for CTD patients.
26316708 Paget's disease of bone: an osteoimmunological disorder? 2015 Osteoimmunology represents a large area of research resulting from the cross talk between bone and immune systems. Many cytokines and signaling cascades are involved in the field of osteoimmunology, originating from various cell types. The RANK/receptor activator of nuclear factor Kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling has a pivotal role in osteoimmunology, in addition to proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1, IL-6, and IL-17. Clinically, osteoimmunological disorders, such as rheumatoid arthritis, osteoporosis, and periodontitis, should be classified according to their pattern of osteoimmunological serum biomarkers. Paget's disease of bone is a common metabolic bone disorder, resulting from an excessively increased bone resorption coupled with aberrant bone formation. With the exception of the cellular responses to measles virus nucleocapsid protein and the interferon-gamma signature, the exact role of the immune system in Paget's disease of bone is not well understood. The cytokine profiles, such as the increased levels of IL-6 and the interferon-gamma signature observed in this disease, are also very similar to those observed in other osteoimmunological disorders. As a potential osteoimmunological disorder, the treatment of Paget's disease of bone may also benefit from progress made in targeted therapies, in particular for receptor activator of nuclear factor Kappa-B ligand and IL-6 signaling inhibition.
26133577 p62 regulates CD40-mediated NFκB activation in macrophages through interaction with TRAF6 2015 Aug 14 CD40 is a member of the tumor necrosis factor (TNF) receptor family. Activation-induced recruitment of adapter proteins, so-called TNF-receptor-associated factors (TRAFs) to the cytoplasmic tail of CD40 triggers signaling cascades important in the immune system, but has also been associated with excessive inflammation in diseases such as atherosclerosis and rheumatoid arthritis. Especially, pro-inflammatory nuclear factor κB (NFκB) signaling emanating from CD40-associated TRAF6 appears to be a key pathogenic driving force. Consequently, targeting the CD40-TRAF6 interaction is emerging as a promising therapeutic strategy, but the underlying molecular machinery of this signaling axis is to date poorly understood. Here, we identified the multifunctional adaptor protein p62 as a critical regulator in CD40-mediated NFκB signaling via TRAF6. CD40 activation triggered formation of a TRAF6-p62 complex. Disturbing this interaction tremendously reduced CD40-mediated NFκB signaling in macrophages, while TRAF6-independent signaling pathways remained unaffected. This highlights p62 as a potential target in hyper-inflammatory, CD40-associated pathologies.
26094774 IFN-γ licenses CD11b(+) cells to induce progression of systemic lupus erythematosus. 2015 Aug Autoantibodies are a hallmark of autoimmune diseases, such as rheumatoid arthritis, autoimmune hepatitis, and systemic lupus erythematosus (SLE). High titers of anti-nuclear antibodies are used as surrogate marker for SLE, however their contribution to pathogenesis remains unclear. Using murine model of SLE and human samples, we studied the effect of immune stimulation on relapsing of SLE. Although autoantibodies bound to target cells in vivo, only additional activation of CD8(+) T cells converted this silent autoimmunity into overt disease. In mice as well as in humans CD8(+) T cells derived IFN-γ enhanced expression of Fc-receptors on CD11b(+) cells. High expression of Fc-receptors allowed CD11b(+) cells to bind to antibody covered target cells and to destroy them in vivo. We found that autoantibodies induce clinically relevant disease when adaptive immunity, specific for disease non-related antigen, is activated.
26069858 In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe. 2015 Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases, although the exact mechanism is yet to be explored. Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care. The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe. Herein, we report the first in vivo CB2R-targeted NIR inflammation imaging study using a synthetic fluorescent probe developed in our laboratory, NIR760-mbc94. In vitro binding assay and fluorescence microscopy study indicate NIR760-mbc94 specifically binds towards CB2R in mouse RAW264.7 macrophage cells. Furthermore, in vivo imaging was performed using a Complete Freund's Adjuvant (CFA)-induced inflammation mouse model. NIR760-mbc94 successfully identified inflamed tissues and the probe uptake was blocked by a CB2R ligand, SR144528. Additionally, immunofluorescence staining in cryosectioned tissues validated the NIR760-mbc94 uptake in inflamed tissues. In conclusion, this study reports the first in vivo CB2R-targeted inflammation imaging using an NIR fluorescent probe. Specific targeting of NIR760-mbc94 has been demonstrated in macrophage cells, as well as a CFA-induced inflammation mouse model. The combined evidence indicates that NIR760-mbc94 is a promising inflammation imaging probe. Moreover, in vivo CB2R-targeted fluorescence imaging may have potential in the study of inflammation-related diseases.
26044312 Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases: A Nationwide Registry-Based Co 2015 Nov BACKGROUND & AIMS: Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients with alcoholic cirrhosis vs controls in Denmark. METHODS: We collected data from nationwide health care registries to identify and follow up all citizens of Denmark diagnosed with alcoholic cirrhosis from 1977 through 2010. Each patient was matched with 5 random individuals from the population (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS: Of the 24,679 patients diagnosed with alcoholic cirrhosis, 532 developed an autoimmune disease, yielding an overall increased adjusted incidence rate ratio (aIRR) of 1.36 (95% confidence interval [CI], 1.24-1.50). The strongest associations were with Addison's disease (aIRR, 2.47; 95% CI, 1.04-5.85), inflammatory bowel disease (aIRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate for polymyalgia rheumatica decreased in patients with alcoholic cirrhosis compared with controls (aIRR, 0.47; 95% CI, 0.33-0.67). CONCLUSIONS: Based on a nationwide cohort study of patients in Denmark, alcoholic cirrhosis is a risk factor for several autoimmune diseases.
25967539 Prescription pain medications and chronic headache in Denmark: implications for preventing 2015 Jul PURPOSE: The aim of the present paper is to study which prescription pain medications are most commonly dispensed to people with chronic headache (CH), particularly those with medication-overuse headache (MOH). METHODS: This cross-sectional study analysed prescription pain medications dispensed within 1 year to 68,518 respondents of a national health survey. Participants with headache ≥ 15 days per month for 3 months were classified as having CH. Those with CH and over-the-counter analgesic use ≥ 15 days per month or purchase of ≥ 20 or ≥ 30 defined daily doses (DDDs) of prescription pain medication per month (depending on the drug) were classified as having MOH. Associations between CH and other chronic pain conditions were analysed by logistic regression. RESULTS: Among those with CH (adjusted prevalence 3.3%, CI 3.2-3.5%), pain medications most commonly dispensed were paracetamol, tramadol, ibuprofen and codeine. CH was associated with osteoarthritis, back pain, and rheumatoid arthritis. Among those with MOH, 32.4% were dispensed an opioid at least once within 1 year. Only 5.1% of people with CH were dispensed triptans. CONCLUSIONS: High prevalence of opioid use among people with CH may be due to inappropriate headache treatment or development of MOH among those treated for other pain conditions. While there were cases of triptan overuse, triptans remain underutilized among those with CH, suggesting that migraine may be under-recognized and inappropriately treated, leading to overuse of other medications. Education of physicians on appropriate headache management is essential for MOH prevention. There is a need to increase universal awareness about MOH as an adverse effect of long-term analgesic use.
25666936 Prospective population-based study of the association between vitamin D status and inciden 2015 Sep Beside its traditional role in skeletal health, vitamin D is believed to have multiple immunosuppressant properties, and low vitamin D status has been suggested to be a risk factor in the development of autoimmune disease. We investigated the association between vitamin D status and development of autoimmune disease. We included a total of 12,555 individuals from three population-based studies with measurements of vitamin D status (25-hydroxy vitamin D). We followed the participants by linkage to the Danish National Patient Register (median follow-up time 10.8 years). Relative risks of autoimmune disease were estimated by Cox regression and expressed as hazard ratios, HRs (95 % confidence intervals CIs). There were 525 cases of incident autoimmune disease. The risk for a 10 nmol/l higher vitamin D was: for any autoimmune disease (HR = 0.94 % CI 0.90, 0.98); thyrotoxicosis (HR = 0.83, 95 % CI 0.72, 0.96); type 1 diabetes (HR = 0.95, 95 % CI 0.88, 1.02), multiple sclerosis (HR = 0.89, 95 % CI 0.74, 1.07), iridocyclitis (HR = 1.00, 95 % CI 0.86, 1.17); Crohn's disease (HR = 0.95, 95 % CI 0.80, 1.13), ulcerative colitis (HR = 0.88, 95 % CI 0.75, 1.04); psoriasis vulgaris (HR = 0.99, 95 % CI 0.86, 1.13); seropositive rheumatoid arthritis (HR = 0.97, 95 % CI 0.89, 1.07), and polymyalgia rheumatica (HR = 0.94, 95 % CI 0.83, 1.06). We found statistically significant inverse associations between vitamin D status and development of any autoimmune disease and thyrotoxicosis in particular. Our findings suggest a possible protective role of a higher vitamin D status on autoimmune disease but warrant further studies to clarify causality.
25510261 Comorbidity profiles in association with vitiligo: a nationwide population-based study in 2015 Jul BACKGROUND: The previous literature has demonstrated the association of autoimmune and atopic diseases with vitiligo, but there has been no large-scale nationwide study conducted to confirm this. OBJECTIVES: The present study was conducted to clarify the comorbid profiles in vitiligo patients and thereby better understand their clinical scenarios and underlying pathogenesis. METHODS: This was a retrospective population-based study conducted from 1996 to 2011 via the National Health Insurance Research Database in Taiwan. The differences in the prevalence of multiple autoimmune and atopic diseases between case subjects and controls were analysed by multiple logistic regression method. RESULTS: A total of 14883 vitiligo patients and 59532 controls were enroled. The prevalence of vitiligo was 0.064% and the peak of onset age was 40-59 years old. The non-stratified analysis evidenced a significant association between vitiligo and several comorbid diseases, including alopecia areata, Hashimoto thyroiditis, myasthenia gravis, psoriasis, Graves' disease, Sjögren's syndrome, systemic lupus erythematosus and atopic dermatitis. Vitiligo patients also had higher prevalence of multiple comorbidities than controls. In the age- and gender-stratified analysis, increased risks of systemic lupus erythematosus and Sjögren's syndrome were observed only in subjects aged 60-79. The association of vitiligo with myasthenia gravis and rheumatoid arthritis was identified only in the subgroup aged 20-39 and in females aged 60-79 respectively. CONCLUSION: Our study not only confirmed the significant association of vitiligo with multiple autoimmune and atopic diseases in Taiwan but also disclosed several unique findings, including the much lower prevalence of vitiligo, delayed onset of vitiligo by three decades, different associated comorbidity profiles comparing to westerners and the age- and gender-specific approach for the vitiligo-associated comorbidities.
25253568 Serum ferritin level correlates with SLEDAI scores and renal involvement in SLE. 2015 Jan INTRODUCTION: Ferritin is an acute-phase reactant that is elevated in various autoimmune disorders. Serum ferritin levels have been positively correlated with disease activity scores of rheumatoid arthritis and systemic lupus erythematosus (SLE). Further, enhanced levels of ferritin have also been reported in lupus nephritis. However, there are no reports from the Indian subcontinent. METHODS: Seventy-six female SLE patients, diagnosed on the basis of revised ACR criteria, and 50 healthy females, age matched from similar geographical areas, were enrolled in the present study. Serum levels of ferritin, IFN-α and IL-6 were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedure. RESULTS: Serum ferritin levels were significantly higher in SLE patients compared to healthy controls (p < 0.0001). Ferritin levels positively correlated with SLE Disease Activity Index (SLEDAI) (p = 0.001, r = 0.35), anti-dsDNA (p = 0.001, r = 0.35), IFN-α (p < 0.0001, r = 0.51) and IL-6 (p < 0.0001, r = 0.65) and negatively correlated with C3 (p = 0.0006, r = -0.38) and C4 (p = 0.01, r = -0.28). Interestingly, serum levels of ferritin were positively associated with proteinuria (p = 0.001, r = 0.36), serum urea (p = 0.0004, r = 0.39) and serum creatinine (p = 0.0006, r = 0.38). CONCLUSION: Serum ferritin is an excellent marker of disease activity and renal dysfunction in SLE.