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ID PMID Title PublicationDate abstract
24830475 Disease or no disease? Disagreement on diagnoses between self-reports and medical records 2015 Mar BACKGROUND: Previous studies reported moderate to good agreement between patients' self-reported diseases and physicians' registered diseases. Disagreement might hamper a good doctor-patient relationship and hamper good quality of care. Disagreement can be associated with demographic and psychosocial patient characteristics. OBJECTIVES: To evaluate the level of agreement on reported chronic diseases between patients and their general practitioners (GPs); to assess whether disagreement relates to patient characteristics. METHODS: This study is embedded in a large GP based prospective cohort. Questionnaires of 2893 patients reporting on 14 chronic diseases are used. The agreement (percentage) between self-reported chronic diseases and the medical records was assessed first by descriptive statistics. To control for agreement by chance alone Cohen's kappa value was calculated. Type of (dis) agreement was further evaluated and associated with patient characteristics. RESULTS: Despite high agreement on diseases between patients and GPs, kappa's varied from 0.17 (inflammatory joint diseases and rheumatoid arthritis) to 0.86 (diabetes mellitus). Most often under-reporting and over-reporting was related to a decreased physical and mental quality of life and higher age. CONCLUSION: kappa values between patients and GPs appeared to be low in this study.
27671547 Active immunization with human interleukin-15 induces neutralizing antibodies in non-human 2016 Sep 26 BACKGROUND: Interleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL-15 consisted in active immunization with structurally modified human IL-15 (mhIL-15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non-human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund's Adjuvant. RESULTS: Immunization with mhIL-15 elicited a specific antibodies response that neutralized native IL-15-dependent biologic activity in a CTLL-2 cell proliferation assay. The highest neutralizing response was obtained in macaques immunized with mhIL-15 adjuvanted in Alum. This response, which was shown to be transient, also inhibited the activity of simian IL-15 and did not affect the human IL-2-induced proliferation of CTLL-2 cells. Also, in a pool of synovial fluid cells from two Rheumatoid Arthritis patients, the immune sera slightly inhibited TNF-α secretion. Finally, it was observed that this vaccine candidate neither affect animal behavior, clinical status, blood biochemistry nor the percentage of IL-15-dependent cell populations, specifically CD56(+) NK and CD8(+) T cells. CONCLUSION: Our results indicate that vaccination with mhIL-15 induced neutralizing antibodies to native IL-15 in non-human primates. Based on this fact, we propose that this vaccine candidate could be potentially beneficial for treatment of diseases where IL-15 overexpression is associated with their pathogenesis.
27630714 Risk of Malignant Neoplasm in Patients with Incident Rheumatoid Arthritis 1980-2007 in rel 2016 Objective. To determine whether the incidence of malignancy is increased in patients with rheumatoid arthritis (RA) compared to a matched comparison cohort and to identify risk for any individual malignancy in RA. Methods. A cohort of 813 Olmsted County, Minnesota, residents who first fulfilled 1987 ACR criteria for RA in 1980-2007 was previously identified by medical record review. Medical records of 813 RA cases and a comparison cohort of age and sex matched Olmsted County residents without RA were evaluated retrospectively for cancer occurrence. Patients in both cohorts were followed until death, migration from Olmsted County, or 12/31/2014. Results. The RA and non-RA cohorts (mean age at incidence/index date: 55.9 [SD: 15.7] years; 68.4% females in both cohorts) were followed on average of 14.1 (SD: 7.7) and 14.9 (SD: 8.1) years, respectively. Prior to RA incidence/index date, 52 RA patients and 66 non-RA subjects had malignancies excluding NMSC (p = 0.21). During follow-up, significantly more malignancies occurred in patients with RA (n = 143) than in comparator subjects (n = 118; hazard ratio: 1.32; p = 0.027). Inclusion of NMSC obviated this difference. Conclusion. After excluding NMSC, there was a small to moderately increased risk of malignancies in patients with RA. Cancer surveillance is imperative in all patients with RA.
26755811 Hepatorenal syndrome in hospitalized patients with chronic liver disease: results from the 2016 Jan Hepatorenal syndrome (HRS) is one of the leading causes of hospitalizations in patients with chronic liver disease (CLD). We conducted a retrospective national database study to determine the epidemiology of HRS in hospitalized patients with CLD. Data from a Nationwide Inpatient Sample were extracted from 2002 to 2012 using ICD-9-CM codes related to CLD and HRS. The following outcomes were examined: in-hospital mortality, total charges, length of stay (LOS), patient demographics, procedures, complications, and comorbidities. Statistical analysis including regression was performed to examine factors associated with HRS. During 2002-2012, hospital discharges related to CLD increased from 407,246 to 836,475 with an increase of 37.9% for HRS as a complication in this population. Patients with CLD and HRS had worse outcomes compared with patients with CLD without HRS. This was manifested as a higher mortality rate (32.0% vs 10.3%), increased LOS (median 7 vs 5 days), and increased hospital costs (median $16,000 vs $11,000). Logistic regression demonstrated that HIV/AIDS (adjusted OR 2.9, 95% CI 2.2 to 3.9), pneumonia (aOR 2.8, 95% CI 2.3 to 3.2), and esophageal variceal bleeding (aOR 1.9, 95% CI 1.7 to 2.0) were associated with higher mortality in patients with HRS. Conversely, liver transplantation (aOR 0.1, 95% CI 0.1 to 0.1), transjugular intrahepatic portosystemic shunt (aOR 0.5, 95% CI 0.4 to 0.6), and hospitalization in the Midwest region of the USA (aOR 0.7, 95% CI 0.6 to 0.7) were associated with reduced mortality. The incidence of HRS in hospitalized patients with CLD increased during 2002-2012. HRS is associated with significant mortality and morbidity in these patients.
26024006 Increased risk of intracerebral hemorrhage among patients with chronic osteomyelitis. 2015 Dec OBJECT: Inflammation may provoke cerebral arteriolar ectasia, inducing microaneurysm formation and further promoting intracerebral hemorrhage (ICH). Chronic osteomyelitis (COM) is an inflammatory disorder for which study of its role in ICH is lacking. This study explored whether COM increases the risk of ICH. METHODS: From Taiwan national insurance inpatient claims, 22,052 patients who were newly diagnosed with COM between 1997 and 2010 were identified; 88, 207 age and sex frequency-matched subjects without COM were selected at random for comparison. Risks of ICH associated with COM and comorbidities, including hypertension, diabetes, hyperlipidemia, chronic kidney disease, and drug abuse, were assessed by the end of 2010. RESULTS: The incidence of ICH was 1.68 times higher in the COM cohort than in the comparison cohort, with an adjusted hazard ratio (HR) of 1.50 (95% CI 1.29-1.74) estimated in the multivariable Cox model. Age-specific analysis showed that the HR of ICH for COM patients decreased with age, with an adjusted HR of 3.28 (95% CI 1.88-5.75) in the < 40-year age group, which declined to 1.11 (95% CI 0.88-1.40) in the elderly. The incidence of ICH increased with the severity of COM; for those with severe COM the adjusted HR was 4.42 (95% CI 3.31-5.89). For subjects without comorbidities, the incidence of ICH was 1.20-fold (95% CI 1.00-1.45) higher in the COM cohort than in the comparison cohort. CONCLUSIONS: This study suggests for the first time that COM is an inflammatory factor associated with increased risk of ICH, especially in younger patients.
25427174 Surrogate target cells expressing surface anti-idiotype antibody for the clinical evaluati 2015 SM03, a chimeric antibody that targets the B-cell restricted antigen CD22, is currently being clinically evaluated for the treatment of lymphomas and other autoimmune diseases in China. SM03 binding to surface CD22 leads to rapid internalization, making the development of an appropriate cell-based bioassay for monitoring changes in SM03 bioactivities during production, purification, storage, and clinical trials difficult. We report herein the development of an anti-idiotype antibody against SM03. Apart from its being used as a surrogate antigen for monitoring SM03 binding affinities, the anti-idiotype antibody was engineered to express as fusion proteins on cell surfaces in a non-internalizing manner, and the engineered cells were used as novel "surrogate target cells" for SM03. SM03-induced complement-mediated cytotoxicity (CMC) against these "surrogate target cells" proved to be an effective bioassay for monitoring changes in Fc functions, including those resulting from minor structural modifications borne within the Fc-appended carbohydrates. The approach can be generally applied for antibodies that target rapidly internalizing or non-surface bound antigens. The combined use of the anti-idiotype antibody and the surrogate target cells could help evaluate clinical parameters associated with safety and efficacies, and possibly the mechanisms of action of SM03.
33132785 A Comparison of Health Disparities among Transgender Adults in Colorado (USA) by Race and 2017 Transgender individuals face heightened risks for discrimination, harassment, and violence that impact their psychosocial well-being and physical health. However, few studies have thoroughly examined the general physical and mental health of transgender adults or within-group health differences by race/ethnicity and income. To that end, after controlling for health insurance status, age, and engagement in exercise, this study asks: (a) are transgender people of color more likely than White transgender individuals to experience poor health outcomes?, and (b) is lower annual household income among transgender adults associated with poorer health outcomes? The current study analyzes secondary data from a survey of transgender adults (N = 417) in one state in the Western United States using multiple linear regression and logistic regression models. Transgender people of color had significantly greater odds than their White counterparts of having arthritis/rheumatoid arthritis/gout/lupus/fibromyalgia, or having asthma, but lower odds of being told by a provider that they had depression. Having a lower income was significantly associated with worse general health as well as multiple indicators of poor physical and mental health, including depression, anxiety, and suicidal ideation. We discuss implications for health care delivery for transgender people and for future research.
27994268 Automated assessment of joint synovitis activity from medical ultrasound and power doppler 2016 OBJECTIVES: Rheumatoid arthritis is the most common rheumatic disease with arthritis, and causes substantial functional disability in approximately 50% patients after 10 years. Accurate measurement of the disease activity is crucial to provide an adequate treatment and care to the patients. The aim of this study is focused on a computer aided diagnostic system that supports an assessment of synovitis severity. MATERIAL AND METHODS: This paper focus on a computer aided diagnostic system that was developed within joint Polish-Norwegian research project related to the automated assessment of the severity of synovitis. Semiquantitative ultrasound with power Doppler is a reliable and widely used method of assessing synovitis. Synovitis is estimated by ultrasound examiner using the scoring system graded from 0 to 3. Activity score is estimated on the basis of the examiner's experience or standardized ultrasound atlases. The method needs trained medical personnel and the result can be affected by a human error. RESULTS: The porotype of a computer-aided diagnostic system and algorithms essential for an analysis of ultrasonic images of finger joints are main scientific output of the MEDUSA project. Medusa Evaluation System prototype uses bone, skin, joint and synovitis area detectors for mutual structural model based evaluation of synovitis. Finally, several algorithms that support the semi-automatic or automatic detection of the bone region were prepared as well as a system that uses the statistical data processing approach in order to automatically localize the regions of interest. CONCLUSIONS: Semiquantitative ultrasound with power Doppler is a reliable and widely used method of assessing synovitis. Activity score is estimated on the basis of the examiner's experience and the result can be affected by a human error. In this paper we presented the MEDUSA project which is focused on a computer aided diagnostic system that supports an assessment of synovitis severity.
26191110 Prevalence of subacromial-subdeltoid bursitis in shoulder pain: an ultrasonographic study. 2015 Jun PURPOSE: The presence of the subacromial-subdeltoid (SASD) bursa inflammation has recently been proposed as a primary radiologic factor predicting persistent limitation and pain in operated patients. The aim of the study was to verify the hypothesis that pain, or increased shoulder pain, could be associated with SASD bursitis not only in operated patients but also in general population. METHODS: A consecutive series of 1940 shoulder ultrasound examinations were performed by our Department over a 5-year period using linear multi-frequency probes. All reports of examination executed for shoulder pain were reviewed. The video clips were independently reviewed by two radiologists: effusion in the SASD bursa and the presence of other pathological conditions were evaluated and confirmed. RESULTS: A total of 1147 shoulder video clips were re-evaluated, and 1587 pathologies were detected; 65.5 % of patients had only one pathology, 30.4 % had two and 4.1 % presented three pathologies. The difference between the group with and without effusion is statistically significant for acromioclavicular joint arthritis, supraspinatus tendon calcific tendinopathy, full-thickness and superficial tear of the supraspinatus, traumas and rheumatoid arthritis with a p value <0.01. CONCLUSIONS: Our study shows that the effusion in the SASD bursa is frequently associated with shoulder pain often independently from the underlying pathology; further studies are needed to confirm the statistical significance of this relationship by clarifying possible confounding factors.
25954655 A Rare Case of Mixed Connective Tissue Disease (MCTD) with Intricate Features of Lupus, Po 2015 Mar Mixed connective tissue disease (MCTD) includes clinical and laboratorial manifestations of systemic lupus erythematosus, scleroderma and polymyositis along with high titres of anti-U1RNP antibodies. In the initial phases of the disease, muscle enzyme levels increase but the disease remains generally subclinical. Presentation with myositis is uncommon. Our objective is to report a rare case of a patient who presented with a severe onset of myositis characterized by dysphagia, an increase in myopathy and joint involvement suggestive of RA. The patient was initiated on pulse corticosteroid therapy along with methotrexate in view of her elevated Creatine Kinase levels and biopsy findings that were suggestive of severe myositis. The patient showed clinical and laboratory improvement with this regimen. Though severe myositis and arthritis can occur in overlap syndrome, MCTD evolved as a separate disease entity due to presence of high titres of Anti U1-RNP antibodies. The authors emphasize that this is an extremely rare presentation of MCTD with only two previous cases seen in literature, one of a 13 year old child and the other being an adult female both of whom had evidence of myositis on presentation.
25687751 Pharmaceutical aspects of anti-inflammatory TNF-blocking drugs. 2015 Jun Tumor necrosis factor (TNF) is a key regulator of inflammatory processes in several immune-mediated inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. Inactivating TNF has been found to be a plausible approach in treating these conditions. Two major strategies have been adopted by scientists to inactivate TNF: one is to use monoclonal antibodies (mAbs) that bind to TNF, and the other is to use fusion proteins that bind to TNF, both inactivate TNF and help to prevent TNF-mediated inflammatory processes. Monoclonal antibodies (mAbs) are biological products that selectively bind to specific antigen molecules, and fusion proteins are soluble receptors that bind to TNF. These types of drugs are generally known as biologics and there has been an explosion in the development and testing of biologics since the 1994 US approval and launch of abciximab, a mAb that binds to GPIIb/IIIa on platelets. Anti-TNF drugs that are currently approved by FDA for treating inflammatory conditions include adalimumab, certolizumab pegol, golimumab, infliximab and etanercept. Since these agents are complex protein molecules, the pharmacodynamics and pharmacokinetics of these drugs are different from small-molecule anti-inflammatory agents. This review focuses on the pharmaceutical aspects of these drugs such as mechanism of action, adverse effects, pharmacokinetics and drug interactions. An effort was also taken to compare the pharmacodynamics and pharmacokinetic properties of these drugs, with the available data at this time.
27186693 Systems-level analysis of genome wide association study results for a pilot juvenile idiop 2015 Jul Genome wide association studies (GWAS) determine susceptibility profiles for complex diseases. In this study, GWAS was performed in 26 patients with oligo and rheumatoid factor negative polyarticular juvenile idiopathic artritis (JIA) and their healthy parents by Affymetrix 250K SNP arrays. Biological function and pathway enrichment analysis was done. This is the first GWAS reported for JIA families from the eastern Mediterranean population. Enrichment of FcγR-mediated phagocytosis pathway and response to various stimuli were the leading discoveries, along with the presentation of the strong interaction of JIA-associated genes with HLA cluster in the co-expression network. The co-expression network also presented the direct interaction of a gene in FcγRmediated phagocytosis pathway, namely GAB2, with BLK, CDH13, IL4R and MICA. The systems biology approach helped us to investigate the interactions between the identified genes and biological pathways and molecular functions, expanding our understanding of JIA pathogenesis at molecular level.
27747810 Estimating the Economic Burden of Rheumatoid Arthritis in Taiwan Using the National Health 2016 Mar BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of the joints. OBJECTIVES: This research aims to estimate the economic burden of RA in Taiwan. METHODS: The National Health Insurance Research Database (NHIRD), a claims-based dataset encompassing 99 % of Taiwan's population, was applied. We used a micro-costing approach for direct healthcare costs and indirect social costs by estimating the quantities and prices of cost categories. Direct costs included surgeries, hospitalizations, medical devices and materials, laboratory tests, and drugs. The costs and quantities of the direct economic burden were calculated based on 2011 data of NHIRD. We identified RA patients and a control cohort matched 1:4 on demographic and clinical covariates to calculate the incremental cost related to RA. Indirect costs were evaluated by missed work (absenteeism) and worker productivity (presenteeism). For the indirect burden, we estimated the rate of absenteeism and presenteeism from a patient survey. Costs were presented in US dollars (US$1 = 30 TWD). RESULTS: A total of 41,269 RA patients were included in the database with incremental total direct cost of US$86,413,971 and indirect cost of US$138,492,987. This resulted in an average incremental direct cost of US$2050 per RA patient. Within direct costs, the largest burdens were associated with drugs (US$73,028,944), laboratory tests (US$6,132,395), and hospitalizations (US$3,208,559). For indirect costs, absenteeism costs and presenteeism costs were US$16,059,681 and US$114,291,687, respectively. CONCLUSIONS: The economic burden of RA in Taiwan is driven by indirect healthcare costs, most notably presenteeism.
26346244 Fcγ and Complement Receptors and Complement Proteins in Neutrophil Activation in Rheumato 2015 Rheumatoid arthritis (RA) is a highly disabling disease that affects all structures of the joint and significantly impacts on morbidity and mortality in RA patients. RA is characterized by persistent inflammation of the synovial membrane lining the joint associated with infiltration of immune cells. Eighty to 90% of the leukocytes infiltrating the synovia are neutrophils. The specific role that neutrophils play in the onset of RA is not clear, but recent studies have evidenced that they have an important participation in joint damage and disease progression through the release of proteolytic enzymes, reactive oxygen species (ROS), cytokines, and neutrophil extracellular traps, in particular during frustrated phagocytosis of immune complexes (ICs). In addition, the local and systemic activation of the complement system contributes to the pathogenesis of RA and other IC-mediated diseases. This review discusses (i) the participation of Fcγ and complement receptors in mediating the effector functions of neutrophils in RA; (ii) the contribution of the complement system and ROS-dependent and ROS-independent mechanisms to joint damage in RA; and (iii) the use of plant extracts, dietary compounds, and isolated natural compounds in the treatment of RA, focusing on modulation of the effector functions of neutrophils and the complement system activity and/or activation.
27734231 The significance and predictive value of free light chains in the urine of patients with c 2016 Dec In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p < 0.001; λ, r = 0.398, p < 0.001) and erythrocyte sedimentation rate (κ, r = 0.692, p < 0.001; λ, r = 0.612, p < 0.001). Patients being treated with rituximab displayed FLC levels similar to those of the reference group. There were clear elevations in both κ and λ FLCs in patients with rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.
27473820 Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases. 2016 Sep The Janus kinase (JAK) family of non-receptor protein-tyrosine kinases consists of JAK1, JAK2, JAK3, and TYK2 (tyrosine kinase-2). Each of these proteins contains a JAK homology pseudokinase (JH2) domain that regulates the adjacent protein kinase domain (JH1). JAK1/2 and TYK2 are ubiquitously expressed whereas JAK3 is found predominantly in hematopoietic cells. The Janus kinase family is regulated by numerous cytokines including interleukins, interferons, and hormones such as erythropoietin, thrombopoietin, and growth hormone. Ligand binding to cytokine and hormone receptors leads to the activation of associated Janus kinases, which then mediate the phosphorylation of the receptors. The SH2 domain of STATs (signal transducers and activators of transcription) binds to the receptor phosphotyrosines thereby promoting STAT phosphorylation by the Janus kinases and consequent activation. STAT dimers are translocated to the nucleus where they participate in the regulation of the expression of thousands of proteins. JAK-STAT dysregulation results in autoimmune disorders such as rheumatoid arthritis, ulcerative colitis, and Crohn disease. JAK-STAT dysregulation also plays a role in the pathogenesis of myelofibrosis, polycythemia vera, and other myeloproliferative illnesses. An activating JAK2 V617F mutation occurs in 95% of people with polycythemia vera and in a lower percentage of people with other neoplasms. JAK1/3 signaling participates in the pathogenesis of inflammatory afflictions while JAK1/2 signaling participates in the development of several malignancies including leukemias and lymphomas as well as myeloproliferative neoplasms. Tofacitinib is a pan-JAK inhibitor that is approved by the FDA for the treatment of rheumatoid arthritis and ruxolitinib is a JAK1/2 inhibitor that is approved for the treatment of polycythemia vera and myelofibrosis.
27297081 Clinical analysis of preoperative risk factors for the incidence of deep venous thromboemb 2016 Jun 13 BACKGROUND: The purpose of this study aimed to assess preoperative risk factors for the incidence of deep venous thromboembolism in patients undergoing posterior lumbar interbody fusion (PLIF). METHODS: The diagnosis of preoperative deep vein thrombosis (DVT) was confirmed by Doppler ultrasonography. To examine the preoperative risk factors for DVT admitted for PLIF, comparative analysis of the DVT-positive and DVT-negative groups was done. RESULTS: DVT was detected in 9.4 % (269/2861) patients, including 17 proximal DVT patients (6.3 %) and 252 the distal DVT patients (93.7 %). According to multivariate logistic regression analysis, the age, preoperative D-dimer, and history of rheumatoid arthritis were significant risk factors relative to the onset of DVT after posterior lumbar surgery. CONCLUSIONS: According to the result of our study, age, positive preoperative plasma D-dimer level, and rheumatoid arthritis had the influential impact on the incidence of DVT admitted for PLIF.
26872110 Primary sclerosing cholangitis associated with inflammatory bowel disease: an observationa 2016 May BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease (IBD). Medical treatment for PSC is still disappointing, whereas immunomodulators and biologics have been proven to be effective in IBD. AIMS: This study aimed to analyze (i) the natural history of patients with PSC with or without IBD and (ii) the long-term efficacy of biologics in patients with PSC and concomitant IBD or rheumatological disorders. PATIENTS AND METHODS: This study included 92 consecutive PSC patients, 50 (54.3%) men and 42 (45.7%) women, with a mean age of 32.0±14.3 years at diagnosis and a mean follow-up duration of 103.8±86 months. Forty-nine (53.3%) patients had associated IBD (38 ulcerative colitis, 10 Crohn's disease, one indeterminate colitis). RESULTS: No significant differences were found between PSC patients with and without associated IBD in terms of liver transplantation, cancer, and death rates. Cholangiocarcinoma was only identified among patients with PSC alone, whereas other cancers (hepatocellular carcinoma, colorectal, and gallbladder cancer) were found only in the group with associated IBD. Five PSC patients were treated with biologic agents: three with adalimumab and one with infliximab for IBD or for rheumatoid arthritis, and one patient with rituximab for rheumatoid arthritis. Adalimumab decreased alkaline phosphatase in two of three patients after 6 and 12 months, infliximab reduced γ-glutamyltransferase after 6 and 12 months, but liver function tests tended to deteriorate thereafter. Cholangiography changes remained stable in all patients. CONCLUSION: Biologic agents may improve liver function tests in PSC patients, but may be associated with adverse events including deterioration of liver function.
26053887 Ocular Inflammation in the Setting of Concomitant Systemic Autoimmune Conditions in an Old 2015 Jul PURPOSE: This retrospective cross-sectional study was designed to investigate the frequency and types of inflammatory ocular manifestations of specific systemic autoimmune diseases in a South Florida Veterans Affairs Hospital population. METHODS: Demographic and medical diagnosis information was extracted from the Veterans Administration database for 1225 patients. These patients were seen in Miami and Broward Veterans Affairs hospitals between April 18, 2008, and April 17, 2013, and were diagnosed with at least 1 of the following: systemic lupus erythematosus, sarcoid, rheumatoid arthritis, polymyalgia rheumatica, Takayasu arteritis, giant cell arteritis, Kawasaki disease, polyarteritis nodosa, Buerger disease, Henoch-Schonlein purpura, Behcet syndrome, granulomatosis with polyangiitis, other polyarteritis nodosa-associated vasculitides, or arteritis not otherwise specified. RESULTS: Of 1225 patients, 618 were seen in the VA eye clinic and 25 were diagnosed with concomitant inflammatory ocular conditions. Uveitis was the most common, and included 8 cases of anterior, 1 anterior-intermediate, 1 intermediate, 2 panuveitis, and 3 unspecified. Other manifestations included 7 cases of keratitis and 2 each of scleritis, episcleritis, and acute ischemic optic neuropathy. The overall frequency of inflammatory ocular disease was 2%. The diseases associated with the highest frequency of ocular involvement were granulomatosis with polyangiitis (1/8), sarcoid (9/198), giant cell arteritis (2/68), and rheumatoid arthritis (11/576). Of these 25 patients, 9 were diagnosed with eye disease before systemic disease. CONCLUSIONS: In this population, ocular manifestations were rarely the presenting feature of systemic disease, but autoimmune disorders are an important underlying cause of inflammatory eye disease that should be considered on first evaluation, even in this "nontraditional," predominantly male, autoimmune disease population.
25960177 Hydroxyethylene isosteres introduced in type II collagen fragments substantially alter the 2015 Jun 14 Class II major histocompatibility complex (MHC) proteins are involved in initiation of immune responses to foreign antigens via presentation of peptides to receptors of CD4(+) T-cells. An analogous presentation of self-peptides may lead to autoimmune diseases, such as rheumatoid arthritis (RA). The glycopeptide fragment CII259-273, derived from type II collagen, is presented by A(q) MHCII molecules in the mouse and has a key role in development of collagen induced arthritis (CIA), a validated model for RA. We have introduced hydroxyethylene amide bond isosteres at the Ala(261)-Gly(262) position of CII259-273. Biological evaluation showed that A(q) binding and T cell recognition were dramatically reduced for the modified glycopeptides, although static models predicted similar binding modes as the native type II collagen fragment. Molecular dynamics (MD) simulations demonstrated that introduction of the hydroxyethylene isosteres disturbed the entire hydrogen bond network between the glycopeptides and A(q). As a consequence the hydroxyethylene isosteric glycopeptides were prone to dissociation from A(q) and unfolding of the β1-helix. Thus, the isostere induced adjustment of the hydrogen bond network altered the structure and dynamics of A(q)/glycopeptide complexes leading to the loss of A(q) affinity and subsequent T cell response.