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ID PMID Title PublicationDate abstract
28033649 Thrombospondin-derived peptide attenuates Sjögren's syndrome-associated ocular surface in 2017 Apr Sjögren's syndrome is the second most common rheumatic disease in which autoimmune response targets exocrine glands (salivary and lacrimal glands) result in clinical symptoms of dry mouth and dry eye. Inflammation of the lacrimal gland induces tear abnormalities that contribute to the inflammation of the ocular surface, which includes ocular mucosa. Thrombospondin-1 (TSP-1) plays a critical regulatory role in the ocular mucosa and as such TSP-1(-/-) mice develop spontaneously chronic ocular surface inflammation associated with Sjögren's syndrome. The autoimmune pathology is also accompanied by a peripheral imbalance in regulatory (T(reg) ) and inflammatory Th17 effectors. In this study, we demonstrate an in-vitro effect of a CD47-binding TSP-derived peptide in the induction of transforming growth factor (TGF)-β1-secreting forkhead box protein 2 (Foxp3(+) ) T(regs) from activated CD4(+) CD25(-) T cells and the inhibition of pathogenic T helper type 17 (Th17)-promoting interleukin (IL)-23 derived from antigen-presenting cells. The in-vivo administration of this peptide promotes Foxp3(+) T(reg) induction and inhibition of Th17 development. Consistent with these results, topical administration of CD47-binding TSP peptide, both before and after the onset of the disease, attenuates clinical symptoms of SS-associated dry eye in TSP-1(-/-) mice. Augmented expression of Foxp3 detected in the draining lymph nodes of TSP peptide -treated mice compared to those treated with control peptide suggests the ability of TSP peptide to restore peripheral immune imbalance. Thus, our results suggest that TSP-derived peptide attenuates Sjögren's syndrome-associated dry eye and autoimmune inflammation by preventing Th17 development while promoting the induction of T(regs) . Collectively, our data identify TSP-derived peptide as a novel therapeutic option to treat autoimmune diseases.
27908305 Abatacept treatment of patients with primary Sjögren's syndrome results in a decrease of 2017 Mar OBJECTIVES: The aim of this study was to assess the histopathological changes in parotid gland tissue of primary Sjögren's syndrome (pSS) patients treated with abatacept. METHODS: In all 15 pSS patients included in the open-label Active Sjögren Abatacept Pilot (ASAP, 8 abatacept infusions) study parotid gland biopsies were taken before treatment and at 24 weeks of follow up. Biopsies were analysed for pSS-related histopathological features and placed in context of clini- cal responsiveness as assessed with EULAR Sjögren's syndrome disease activity index (ESSDAI). RESULTS: Abatacept treatment resulted in a decrease of germinal centres (GCs)/ mm2 (p=0.173). Number of GCs/mm2 at baseline was associated with response in the glandular domain of ESSDAI (Spearman ρ=0.644, p=0.009). Abatacept treatment did not reduce focus score, lymphoepithelial lesions, area of lymphocytic infiltrate, amount of CD21+ networks of follicular dendritic cells, and numbers of CD3+ T-cells or CD20+ B- cells. Number of IgM plasma cells/mm2 increased (p=0.041), while numbers of IgA and IgG plasma cells/mm2 were unaffected during abatacept treatment. CONCLUSIONS: Abatacept affects formation of GCs of pSS patients in parotid glands, which is dependent on co-stimulation of activated follicular-helper-T-cells. Herewith, local formation of (autoreactive) memory B-cells is inhibited. Presence of GCs at baseline predicts responsiveness to abatacept in the ESSDAI glandular domain.
28283842 A pharmaceutical study on lornoxicam fast disintegrating tablets: formulation and in vitro 2017 Jun Lornoxicam is an anti-inflammatory drug used to relieve rheumatoid arthritis pain, but the low water solubility and bitter taste of the drug present challenges for formulation as fast disintegrating tablets (FDTs). Complexation of the drug with β-cyclodextrin was initially carried out to increase the drug solubility and to mask its bitter taste. Tablets were prepared by direct compression of drug complex (DC), F-Melt, mannitol, crospovidone, and sodium starch glycolate (SSG). FDTs were characterized in terms of disintegration time (DT) and dissolution. A bioequivalence study was carried out using (Zeficam® tablets (Eva Pharma) as reference with the help of human volunteers (n = 4). The chosen formula (F2, DC 24 mg, F-Melt 88.4 mg, and crospovidone 5 mg) exhibited the shortest in vitro (18 s) and in vivo DT (13 s), and the percent drug released after Q6min was 95.90%. Following administration of F2 and Zeficam®, the respective maximum drug plasma concentrations (C(max)) were 510 and 532.5 ng/mL, at times (T(max)) of 1 and 2.5 h, of mean residence times (MRTs) of 12.25 and 11.35 h and of areas under the plasma curve [AUC(0-24)] of 5080.253 and 4815.775 ng/h/mL. There were significant differences in T(max) and MRT of both treatments (p < 0.05). Moreover, the volunteers found F2 to be palatable. FDTs could be considered as promising dosage forms for lornoxicam as they exhibited a short in vivo DT and an increased rate of drug release and attained a relative bioavailability of 105.49%. This could offer a fast relief of pain accompanying rheumatoid arthritis.
28733032 Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenes 2017 Sep 16 Bones are inflexible yet ever-changing metabolic organs, and bone homeostasis is maintained through two delicately regulated processes: bone construction and bone reabsorption. An imbalance in bone metabolism is linked to most orthopedic diseases, including osteoporosis and rheumatoid arthritis. Importantly, tumor necrosis factor-α (TNF-α) blocks osteoblast differentiation and stimulates osteoclast formation, resulting in delayed deposition of new bone and accelerated bone resorption, especially in rheumatoid arthritis patients with inflammatory conditions. Pilose antler peptide (PAP) isolated and purified from deer antlers has been shown to have beneficial effects on chronic inflammation. In the present study, we studied the impact of PAP on osteoblast differentiation and evaluated the regulatory mechanism, with particular emphasis on the effect of PAP on TNF-α-mediated NF-κB signaling. Mouse primary osteoblast cells were activated with bone morphogenetic protein-2 (BMP-2) for osteoblast differentiation. A significant stimulatory effect of PAP in osteoblastogenesis was observed using ALP activity and Alizarin Red S staining assays. Meanwhile, PAP significantly rescued TNF-α-induced impairment of osteoblast formation as well as mineralization. Furthermore, we found a similar trend upon analyzing osteoblast-specific gene expression. PAP significantly rescued TNF-α-mediated decrease in expression of osteoblast-specific genes. A molecular mechanism assay indicated that PAP significantly inhibited TNF-α-mediated stimulation of NF-κB signaling activity, as well as nuclear translocation of its subunit p65. Moreover, over-expression of p65 reversed the stimulatory effects of PAP on osteoblast differentiation. Furthermore, we also identified that PAP dose dependently inhibit osteoclastogenesis, and this effect might be achieved via suppressing NF-κB activity. In summary, this study shows that PAP promotes osteoblast differentiation and blocks TNF-α-mediated suppression of osteoblastogenesis in vitro via the NF-κB/p65 pathway, as well as inhibits osteoclastsogenesis in vitro. Therefore, PAP, a novel drug with both antiresorptive and osteoanabolic activity, shows therapeutic potential as an alternative treatment for osteolytic diseases, including rheumatoid arthritis and osteoporosis.
28554321 Phosphodiesterase 4 Inhibitors in Immune-mediated Diseases: Mode of Action, Clinical Appli 2017 Phosphodiesterase (PDE) 4 is a superfamily of enzymes that catalyze the hydrolysis of cyclic adenosine 3',5'-monophosphate (cAMP), an intracellular second messenger and regulator of a wide array of genes and proteins. Increased levels of intracellular cAMP lead to activation of genes but also to inhibition of nuclear factor-kappa B, involved in pro-inflammatory responses. By increasing cAMP levels, PDE4 inhibitors, such as apremilast, reduced production of pro-inflammatory TNFα, IFNγ, and IL-17 and increased production of anti-inflammatory IL-10 in lipopolysaccharide-stimulated peripheral blood mononuclear cells, and in patients with psoriatic arthritis (PsA). Among PDE4 inhibitors, apremilast, roflumilast, and crisabolore have been approved for the treatment of psoriasis and PsA, chronic obstructive pulmonary disease, and atopic dermatitis, respectively. In a preliminary study on psoriasis and PsA we showed that at 6 months apremilast decreased IFNγ+CD3+ Th1 cells and IL- 17+CD3+ Th17 cells and increased regulatory B cells and regulatory T cells. In this review, we highlight recent findings of PDE4 inhibitors in atopic dermatitis, alopecia areata, uveitis, rheumatoid arthritis, psoriasis and PsA, systemic lupus erythematosus, vasculitis, systemic sclerosis, multiple sclerosis and inflammatory bowel disease. Given the role of cAMP as second messenger in diverse intracellular pathways, selective PDE4 inhibitors are likely to be therapeutic agents for various immune mediated diseases.
27717524 STA-21, a STAT-3 inhibitor, attenuates the development and progression of inflammation in 2017 Feb We set out to investigate the influence of STA-21, a dynamic STAT-3 inhibitor, on the expansion and progression of rheumatoid arthritis (RA), and to determine its potential mechanisms of action in a mouse model of collagen antibody-induced arthritis (CAIA). To this end, arthritis was induced via intravenous (IV) injection of Balb/c mice with a cocktail of antibodies directed against type II collagen (1.5μg/mouse, IV), followed by lipopolysaccharide (LPS) at a dose of (25μg/mouse, i.p.) on day 3. Mice were then left untreated or were simultaneously treated with STA-21 (0.5mg/kg, i.p., once daily for 2 weeks) followed by evaluation for clinical and histological features of arthritic inflammation and flow cytometric analysis of cytokines and transcription factors in peripheral blood. STA-21 enhanced the clinical course of arthritis in CAIA mice and decreased CD8(+)RORγt(+) and CD8(+)IL-21(+) cells while inducing the production of CD8(+)Foxp3(+) cells. Furthermore, STA-21 prevented the production of TNF-α and IL-6 in peripheral blood and increased IL-27 production by CD14(+) cells. Moreover, STA-21 not only regulates Th1/Th2 serum cytokine levels but also the mRNA and protein expression of key factors including NF-κB p65, RORγt, T-bet, IL-4, GATA-3, JAK1, Stat3, and IL-21. Thus, administration of the Stat3 inhibitor STA-21 inhibits cellular signaling pathways and downstream activation of key transcription factors previously shown to play key roles in the pathogenesis of RA. Therefore, these data suggest that STA-21 could be considered as a potential treatment for patients with RA.
28887050 Genome Engineering for Personalized Arthritis Therapeutics. 2017 Oct Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics.
28148840 Therapy with CTLA4-Ig and an antiviral monoclonal antibody controls chikungunya virus arth 2017 Feb 1 In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics rheumatoid arthritis and can endure for months to years. At present, no approved treatment is effective in preventing or controlling CHIKV infection or disease. We treated mice with eight different disease-modifying antirheumatic drugs and identified CLTA4-Ig (abatacept) and tofacitinib as candidate therapies based on their ability to decrease acute joint swelling. CTLA4-Ig reduced T cell accumulation in the joints of infected animals without affecting viral infection. Whereas monotherapy with CTLA4-Ig or a neutralizing anti-CHIKV human monoclonal antibody provided partial clinical improvement, therapy with both abolished swelling and markedly reduced levels of chemokines, proinflammatory cytokines, and infiltrating leukocytes. Thus, combination CTLA4-Ig and antiviral antibody therapy controls acute CHIKV infection and arthritis and may be a candidate for testing in humans.
28246126 Effect of Disease-Related Changes in Plasma Albumin on the Pharmacokinetics of Naproxen in 2017 May Naproxen (NPX) is used in the treatment of rheumatoid arthritis (RA) for alleviation of pain and inflammation. In view of the extensive albumin binding of NPX, this study investigates whether chronic inflammation and sex influence the physiologic albumin concentrations, plasma protein binding, and pharmacokinetics (PK) of NPX. The PK of NPX was evaluated in a rat model of RA [collagen-induced arthritis (CIA) in Lewis rats] and in healthy controls. These PK studies included 1) NPX in female and male CIA rats that received 10, 25, or 50 mg/kg NPX i.p.; and 2) NPX in healthy female and male rats after i.p. dosing of NPX at 50 mg/kg. Plasma albumin concentrations were quantified by enzyme-linked immunosorbent assay, and protein binding was assessed using ultrafiltration. The NPX concentrations in plasma and filtrates were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma concentration-time data of NPX were first assessed by noncompartmental analysis (NCA). Nonlinear PK as indicated by dose-dependent NCA clearances and distribution volumes was observed. A two-compartment model with a first-order absorption process incorporating nonlinear protein binding in plasma and tissues jointly described the PK data of all groups. Saturable albumin binding accounts for the nonlinearity of NPX PK in all rats as well as part of the PK differences in arthritic rats. The CIA rats exhibited reduced albumin concentrations, reduced overall protein binding, and reduced clearances of unbound NPX, consistent with expectations during inflammation. The net effect of chronic inflammation was an elevation of the C(max) and area under the plasma concentration-time curve (AUC) of unbound drug.
28246127 Modeling Sex Differences in Pharmacokinetics, Pharmacodynamics, and Disease Progression Ef 2017 May Naproxen (NPX) is a frequently used nonsteroidal anti-inflammatory drug for rheumatoid arthritis (RA). Lack of quantitative information about the drug exposure-response relationship has resulted in empirical dosage regimens for use of NPX in RA. Few studies to date have included sex as a factor, although RA predominates in women. A pharmacokinetic, pharmacodynamic, and disease progression model described the anti-inflammatory effects of NPX in collagen-induced arthritic (CIA) male and female rats. Three groups of rats were included for each sex: healthy animals, CIA controls, and CIA rats given a single 50-mg/kg dose of NPX intraperitoneally. Paw volumes of healthy rats indicated natural growth, and disease status was measured by paw edema. An innovative minimal physiologically based pharmacokinetic (mPBPK) model incorporating nonlinear albumin binding of NPX in both plasma and interstitial fluid (ISF) was applied. Arthritic rats exhibited lower plasma and ISF albumin concentrations and reduced clearances of unbound drug to explain pharmacokinetic profiles. The unbound ISF NPX concentrations predicted by the mPBPK model were used as the driving force for pharmacological effects of NPX. A logistic growth function accounting for natural paw growth and an indirect response model for paw edema and drug effects (inhibition of k(in)) was applied. Female rats showed a higher incidence of CIA, earlier disease onset, and more severe symptoms. NPX had stronger effects in males, owing to higher unbound ISF NPX concentrations and lower IC(50) values. The model described the pharmacokinetics, unbound NPX in ISF, time course of anti-inflammatory effects, and sex differences in CIA rats.
29070082 Sex influences eQTL effects of SLE and Sjögren's syndrome-associated genetic polymorphism 2017 Oct 25 BACKGROUND: Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs for both diseases. Many SNPs in the genome are expression quantitative trait loci (eQTLs), with context-dependent effects. Assuming that sex is a biological context, we investigated whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach to understand if they display sex-specific effects. METHODS: We used genome-wide genotype and gene expression data from primary B cells from 125 males and 162 females. The MatrixEQTL R package was used to identify eQTLs within a genomic window of 2 Mb centered on each of 22 established SLE and/or pSS susceptibility SNPs. To find sex-specific eQTLs, we used a linear model with a SNP * sex interaction term. RESULTS: We found ten SNPs affecting the expression of 16 different genes (FDR < 0.05). rs7574865-INPP1, rs7574865-MYO1B, rs4938573-CD3D, rs11755393-SNRPC, and rs4963128-PHRF1 were novel observations for the immune compartment and B cells. By analyzing the SNP * sex interaction terms, we identified six genes with differentially regulated expression in females compared to males, depending on the genotype of SLE/pSS-associated SNPs: SLC39A8 (BANK1 locus), CD74 (TNIP1 locus), PXK, CTSB (BLK/FAM167A locus), ARCN1 (CXCR5 locus), and DHX9 (NCF2 locus). CONCLUSIONS: We identified several unknown sex-specific eQTL effects of SLE/pSS-associated genetic polymorphisms and provide novel insight into how gene-sex interactions may contribute to the sex bias in systemic autoimmune diseases.
28664283 [Positron emission tomography/computed tomography in rheumatology]. 2017 Sep Combined positron emission tomography/computed tomography (PET/CT) is a whole-body imaging procedure, which enables sensitive detection of inflammatory changes. It may be used to simultaneously obtain both precise anatomical and molecular information in order to comprehensively characterize diseases. The glucose analogue (18)F-fluorodeoxyglucose (FDG) represents a universally applicable radiotracer for imaging of inflammatory processes. Its accumulation in tissues can be semiquantitatively characterized by use of standardized uptake values (SUV). In principle, a broad spectrum of infectious and non-infectious inflammatory and malignant diseases can be imaged. (18)F-FDG PET/CT has become a valuable modality and is increasingly being used for evaluation of large vessel vasculitis and for evaluation of elevated systemic inflammatory markers without known cause. Beside the radiotracer (18)F-FDG, other radiopharmaceuticals enable a non-invasive analysis of additional parameters of inflammatory disorders, such as other metabolic pathways or the expression of surface receptors.
28643390 Oral disorders, saliva secretion, and oral health-related quality of life in patients with 2017 Aug Chemosensory function, burning sensations in the tongue (BST), halitosis, saliva secretion, and oral health-related quality of life (OHRQoL) were investigated in patients with primary Sjögren's syndrome (pSS). In 31 patients with pSS and 33 controls, olfactory and gustatory functions were evaluated. Self-reported complaints of dysgeusia, BST, and halitosis were recorded. Saliva secretion rates were measured and OHRQoL was assessed using the short-form Oral Health Impact Profile (OHIP-14). Patients had significantly lower olfactory (8.8 ± 3.5 vs. 10.7 ± 1.2) and gustatory (18.9 ± 7.1 vs. 25.4 ± 4.3) scores than controls, and significantly more patients complained of dysgeusia (58.1% vs. 0%), BST (54.8% vs. 6.1%), and halitosis (41.9% vs. 0%). A significantly greater proportion of patients with pSS had ageusia (19% vs. 0%), hypogeusia (32% vs. 12%), anosmia (13% vs. 0%), or hyposmia (29% vs. 9%). Significantly lower saliva secretion rates (ml min(-1) ) were observed in patients with pSS for stimulated (0.62 ± 0.40 vs. 1.57 ± 0.71) and unstimulated (0.08 ± 0.07 vs. 0.29 ± 0.17) saliva. The mean OHIP-14 score was significantly higher in patients with pSS (16.2 ± 10.8 vs. 2.7 ± 3.1) and was positively correlated with dysgeusia, BST, and halitosis. In conclusion, patients with pSS reported higher occurrence of dysgeusia, BST, and halitosis, and demonstrated relatively impaired chemosensory and salivary functions. The patients' poorer OHRQoL was associated with dysgeusia, BST, and halitosis.
28027754 Correlation between intravoxel incoherent motion MR parameters and MR nodular grade of par 2017 Jan PURPOSE: To explore the correlation between intravoxel incoherent motion (IVIM) magnetic resonance (MR) parameters and MR nodular grade of parotid glands in patients with Sjögren's syndrome (SS). MATERIALS AND METHODS: A total of 31 consecutive patients with SS and 28 gender- and age-matched healthy volunteers underwent bilateral parotid 3.0T MR examination including the IVIM sequence (9 b values, 0-800s/mm(2)). The apparent diffusion coefficient (ADC), diffusion coefficient D, pseudo-diffusion coefficient D(*), and perfusion fraction f of bilateral parotid glands were obtained, and the nodular grade of each parotid gland was evaluated according to the MR morphological appearance. RESULTS: Sixty-two parotid glands in 31 patients with SS consisted of 32, 14, 8, and 8 parotid glands at MR nodular grades 0, 1, 2, and 3, respectively. In parotid glands of grade 0, 1, 2, 3 and healthy volunteers, the ADC values were (1.13±0.25, 1.11±0.17, 1.05±0.24, 0.89±0.04 and 1.00±0.21)×10(-3)mm(2)/s, D values were (0.92±0.13, 0.90±0.19, 0.90±0.03, 0.67±0.03, 0.81±0.03)×10(-3)mm(2)/s, f values were 0.20±0.04, 0.18±0.02, 0.15±0.01, 0.11±0.01, 0.15±0.06, and D(*)values were (53.89±28.26, 41.78±16.35, 51.24±18.69, 31.83±18.03, 36.83±16.14)×10(-3)mm(2)/s respectively. The ADC, D, f, and D(*) values of parotid glands in patients with SS at grade 0 were significantly higher than those in healthy volunteers (all P<0.05). Significant differences were observed in the D and f values of parotid glands in patients with SS among different grades (P=0.003,<0.001, respectively). The IVIM parameters (D, f) of parotid glands at early (grades 0-1) and advanced (grades 2-3) stages in patients with SS were significantly higher and lower, respectively, than those in healthy volunteers (all P<0.05). The D and f values inversely correlated with MR nodular grades significantly (r=- 0.297, P=0.019; r=- 0.653, P<0.001, respectively) CONCLUSION: The parotid glands with different MR nodular grades in patients with SS showed different IVIM parameters, reflecting different pathophysiological characteristics of parotid glands at different stages.
28781940 Long-term Treatment with Anti-platelet Agents for Collagen-induced Arthritis Improves Radi 2017 Jun OBJECTIVES: The objectives of this study were to evaluate the long-term effect of anti-platelet treatment on the radiological progression of collagen-induced arthritis in rats. METHODS: Female Lewis rats with collagen-induced arthritis were divided into three experimental groups: saline, aspirin monotherapy (n = 12), and aspirin-clopidogrel dual therapy (n = 12). Drugs were administered daily and continued up to 70 days after the induction of arthritis. The clinical arthritis index (weight, morphology score, and paw thickness) and radiological scores were evaluated. RESULTS: The clinical arthritis index peaked on day 20, while the radiological scores peaked on day 35. No intergroup difference was observed in the clinical arthritis index throughout the experiment. The aspirin-clopidogrel dual therapy group had a significantly higher mean radiological score than the other groups (p = 0.045) on day 35. Further treatments resulted in significantly improved radiological findings in the aspirin monotherapy and aspirin-clopidogrel dual therapy groups on day 70 but no significant improvement in the saline group. CONCLUSION: Anti-platelet agent treatment improved radiological findings on day 70. These observations emphasize the importance of a future long-term study of the effects of anti-platelet agent treatment on arthritis.
28343613 Effects of the use of growth hormone in children and adolescents with juvenile idiopathic 2017 Mar INTRODUCTION: Children with juvenile idiopathic arthritis (JIA) often have impaired growth and short stature. There is evidence that the therapeutic use of growth hormone (GH) is useful and safe in these patients. OBJECTIVE: To analyze the effects of GH use in patients with JIA. METHOD: A systematic review of the literature over the last 18 years in Medline and Embase databases. The criteria were analyzed independently by the researchers. We used the following keywords: "growth hormone", "arthritis, juvenile", "arthritis, rheumatoid", "child" and "adolescent". RESULTS: Among the 192 identified articles, 20 corresponded to the inclusion criteria. Seventeen longitudinal studies and 3 case reports were found. Most studies analyzed observed increased growth, muscle mass and bone mass using GH. Adverse effects observed were glucose intolerance, diabetes, bone deformities, osteonecrosis, reactivation of the disease and low final height. CONCLUSION: The majority of studies reported positive effects after the therapeutic use of GH, but some variability in response to treatment was observed. The combination of growth hormone with other drugs seems to be a good option.
29222450 Elevation of autophagy markers in Sjögren syndrome dry eye. 2017 Dec 8 Autophagy is known to be implicated in the pathogenesis of Sjögren syndrome (SS), but evidences are limited. We aimed to examine the levels of autophagy markers in tear film and conjunctival epithelial cells from SS dry eye patients, and analyze their correlations with clinical features. Patients with SS dry eye exhibited lower Schirmer values, lower tear breakup time, and higher ocular staining scores. In tears, ATG5 and LC3B-II/I levels were significantly higher in SS dry eye. ATG5 and LC3B-II mRNA in the conjunctiva were also elevated in SS dry eye compared with non-SS dry eye. The immunostaining of conjunctival epithelium showed a punctate pattern of ATG5 and LC3B-II in SS dry eye. These staining patterns were also observed in the lacrimal gland of SS animal models. ATG5 levels in tears and the conjunctival epithelium strongly correlated with ocular staining scores, and one month of topical corticosteroid treatment reduced both ATG5 and LC3B-II/I levels in tear film and the conjunctival epithelium of patients with SS dry eye. Our results suggest that autophagy is enhanced or dysregulated in SS and autophagy markers may be serve as both diagnostic and therapeutic biomarkers in SS dry eye.
28722699 Added Value of Parotid R2* Values for Evaluation of Sjögren Syndrome: A Preliminary Study 2017 Jul/Aug OBJECTIVE: To explore the application of parotid R2* values for evaluating Sjögren syndrome (SS). METHODS: Twenty-four consecutive SS patients and 24 sex-matched and age-matched healthy volunteers underwent bilateral parotid 3.0 T magnetic resonance (MR) imaging, including blood oxygenation level dependent sequence. Parotid R2* values of SS patients and volunteers were compared. A receiver operating characteristic analysis was used to evaluate the diagnostic performance of parotid R2* value alone and in combination with MR nodular grade. RESULTS: The left parotid R2* value was significantly lower than the right (P = 0.006) in SS patients. Parotid R2* value in SS patients was significantly lower than that in healthy volunteers (P < 0.001). With a cutoff value of 64.14/s, the sensitivity of the parotid R2* value was 62.5% in the diagnosis of SS. By combining R2* value with MR nodular grade, the sensitivity reached 87.5%. CONCLUSIONS: Parotid R2* value contributed to the diagnosis of Sjögren syndrome combined with MR nodular grade.
28013207 An investigation into the prevalence of sleep disturbances in primary Sjögren's syndrome: 2017 Apr 1 OBJECTIVES: To identify whether sleep disturbances are more prevalent in primary SS (pSS) patients compared with the general population and to recognize which specific sleep symptoms are particularly problematic in this population. METHODS: Electronic searches of the literature were conducted in PubMed, Medline (Ovid), Embase (Ovid), PsychINFO (Ovid) and Web of Science and the search strategy registered a priori . Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria, reference lists were examined and a narrative synthesis of the included articles was conducted. RESULTS: Eight whole-text papers containing nine separate studies met the inclusion criteria and were included in the narrative analysis. Few of these studies met all of the quality assessment criteria. The studies used a range of self-reported measures and objective measures, including polysomnography. Mixed evidence was obtained for some of the individual sleep outcomes, but overall compared with controls, pSS patients reported greater subjective sleep disturbances and daytime somnolence and demonstrated more night awakenings and pre-existing obstructive sleep apnoea. CONCLUSIONS: A range of sleep disturbances are commonly reported in pSS patients. Further polysomnography studies are recommended to confirm the increased prevalence of night awakenings and obstructive sleep apnoea in this patient group. pSS patients with excessive daytime somnolence should be screened for co-morbid sleep disorders and treated appropriately. Interventions targeted at sleep difficulties in pSS, such as cognitive behavioural therapy for insomnia and nocturnal humidification devices, have the potential to improve quality of life in this patient group and warrant further investigation.
28100575 Atrophic pityriasis versicolor occurring in a patient with Sjögren's syndrome. 2017 Jan 18 Pityriasis versicolor is one of the most frequent epidermal mycotic infections in the world, but its atrophic variant is rarely described. The aetiology of the atrophy is still unknown, and two main hypotheses have been formulated, one suggesting a correlation with long-term use of topical steroids and the other a delayed type hypersensitivity to epicutaneous antigens derived from components of the fungus. Atrophic pityriasis versicolor is a benign disease, but needs to be distinguished from other more severe skin diseases manifesting with cutaneous atrophy. The diagnosis can be easily confirmed by direct microscopic observation of the scales soaked in 15% potassium hydroxide, which reveals the typical 'spaghetti and meatball' appearance, or by a skin biopsy in doubtful cases. Here, we describe a case of extensive atrophic pityriasis versicolor occurring in a woman affected by Sjögren's syndrome which completely resolved after topical antifungal treatment.