The Experts below are selected from a list of 38541 Experts worldwide ranked by ideXlab platform
Mary K Crow - One of the best experts on this subject based on the ideXlab platform.
-
expression of long interspersed nuclear element 1 retroelements and induction of type i interferon in patients with Systemic Autoimmune Disease
Arthritis & Rheumatism, 2016Co-Authors: Clio P Mavragani, Irina Sagalovskiy, Adrianos Nezos, Efstathia K Kapsogeorgou, Pin Lu, Jun Liang Zhou, Kyriakos A Kirou, Surya V Seshan, Haralampos M Moutsopoulos, Mary K CrowAbstract:Objective Increased expression of type I interferon (IFN) and a broad signature of type I IFN–induced gene transcripts are observed in patients with Systemic lupus erythematosus (SLE) and other Systemic Autoimmune Diseases. To identify Disease-relevant triggers of the type I IFN pathway, this study sought to investigate whether endogenous virus-like genomic repeat elements, normally silent, are expressed in patients with Systemic Autoimmune Disease, and whether these retroelements could activate an innate immune response and induce type I IFN. Methods Expression of type I IFN and long interspersed nuclear element 1 (LINE-1; L1) was studied by polymerase chain reaction, Western blotting, and immunohistochemistry in samples of kidney tissue from patients with lupus nephritis and minor salivary gland (MSG) tissue from patients with primary Sjogren's syndrome (SS). Induction of type I IFN by L1 was investigated by transfection of plasmacytoid dendritic cells (PDCs) or monocytes with an L1-encoding plasmid or L1 RNA. Involvement of innate immune pathways and altered L1 methylation were assessed. Results Levels of L1 messenger RNA transcripts were increased in lupus nephritis kidneys and in MSG tissue from patients with SS. Transcript expression correlated with the expression of type I IFN and L1 DNA demethylation. L1 open-reading frame 1/p40 protein and IFNβ were expressed in MSG ductal epithelial cells and in lupus nephritis kidneys, and IFNα was detected in infiltrating PDCs. Transfection of PDCs or monocytes with L1-encoding DNA or RNA induced type I IFN. Inhibition of Toll-like receptor 7 (TLR-7)/TLR-8 reduced the induction of IFNα by L1 in PDCs, and an inhibitor of IKKe/TANK-binding kinase 1 abrogated the induction of type I IFN by L1 RNA in monocytes. Conclusion L1 genomic repeat elements represent endogenous nucleic acid triggers of the type I IFN pathway in SLE and SS and may contribute to initiation or amplification of Autoimmune Disease.
-
long interspersed nuclear elements line 1 potential triggers of Systemic Autoimmune Disease
Autoimmunity, 2010Co-Authors: Mary K CrowAbstract:Recent advances have identified immune complexes containing nucleic acids as stimuli for toll-like receptors and inducers of type I interferon (IFN). While a similar mechanism may serve to amplify immune system activation and production of inflammatory mediators in vivo in the context of Systemic Autoimmune Diseases, the initial triggers of autoimmunity have not been defined. In this review, we describe a category of potential inducers of autoimmunity, the endogenous retroelements, with a particular focus on long interspersed nuclear elements (LINE-1, L1). Increased expression of L1 transcripts or decreased degradation of L1 DNA or RNA could provide potent stimuli for an innate immune response, priming of the immune system, and induction of autoimmunity and inflammation. Genomic and genetic variations among individuals, sex-related differences in L1 regulation, and environmental triggers are among the potential mechanisms that might account for increased L1 expression. Induction of type I IFN by L1-enriched nucleic acids through TLR-independent pathways could represent a first step in the complex series of events leading to Systemic Autoimmune Disease.
-
a potential role for microbial superantigens in the pathogenesis of Systemic Autoimmune Disease
Arthritis & Rheumatism, 1991Co-Authors: Steven M. Friedman, David N Posnett, Joseph R Tumang, Mary K Crow, B C ColeAbstract:We have attempted herein to demonstrate how microbial superantigens could promote an abnormal form of "cognate" T helper-B cell interaction, analogous to that which may occur during GVH Disease, leading to B cell activation and Systemic autoimmunity. In vitro studies performed at our laboratory and others have demonstrated that resting human B cells bind microbial superantigens and present them to superantigen-reactive autologous T helper cells, resulting in T cell activation and polyclonal IgM and IgG production by the superantigen-bearing B cells. In vitro studies of microbial superantigen-mediated murine T helper-B cell interactions demonstrate preferential help for B cells that have encountered specific antigen. Both in humans and in mice, the cellular interactions involved and the B cell responses induced are highly analogous to those mediated by allospecific T helper-B cell interaction. Finally, the results of studies carried out on T cell-deficient (nude) mice suggest that microbial superantigens may trigger similar T helper cell-dependent polyclonal IgM and IgG responses in vivo. These mice will be studied over time and tested for the development of autoantibodies characteristic of SLE and of Autoimmune organ system damage, the occurrence of which are predicted by our model.
John L Niles - One of the best experts on this subject based on the ideXlab platform.
-
trojan horses drug culprits associated with antineutrophil cytoplasmic autoantibody anca vasculitis
Current Opinion in Rheumatology, 2014Co-Authors: William F Pendergraft, John L NilesAbstract:Purpose of reviewAntineutrophil cytoplasmic autoantibody (ANCA) vasculitis is a Systemic Autoimmune Disease resulting in small-vessel inflammation caused by pathogenic autoantibodies directed against proteinase 3 or myeloperoxidase. Legal drug culprits have been implicated as causative agents in sec
-
contaminated cocaine and antineutrophil cytoplasmic antibody associated Disease
Clinical Journal of The American Society of Nephrology, 2011Co-Authors: Martina M Mcgrath, Tamara Isakova, Helmut G Rennke, Ann M Mottola, Karen Laliberte, John L NilesAbstract:BACKGROUND AND OBJECTIVES: Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a Systemic Autoimmune Disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cases were identified between March 2009 and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation. RESULTS: Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. CONCLUSIONS: We describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated Systemic Autoimmune Disease. Our data suggest that this is a potentially life-threatening complication of cocaine use.
Peter E Lipsky - One of the best experts on this subject based on the ideXlab platform.
-
comparison of antibody repertoires produced by hiv 1 infection other chronic and acute infections and Systemic Autoimmune Disease
PLOS ONE, 2011Co-Authors: Felix Breden, Peter E Lipsky, Christa Lepik, Nancy S Longo, Marinieve Montero, Jamie K ScottAbstract:Background: Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M)Abs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the VH genes of five of them encode a long ($20 aa) third complementarity-determining region (CDR-H3). This led us to question whether long CDR-H3s and high levels of somatic mutation (SM) are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general. Methodology and Principal Findings: We assembled a VH-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral) infections (ChI), acute (bacterial and viral) infections (AcI), and Systemic Autoimmune Diseases (SAD), and compared their CDR-H3 length, number of SMs and germline VH-gene usage. We found that anti-HIV Abs, regardless of their neutralization breadth, tended to have long CDR-H3s and high numbers of SMs. However, these features were also common among Abs associated with other chronic viral infections. In contrast, Abs from acute viral infections (but not bacterial infections) tended to have relatively short CDR-H3s and a low number of SMs, whereas SAD Abs were generally intermediate in CDR-H3 length and number of SMs. Analysis of VH gene usage showed that ChI Abs also tended to favor distal germline VH-genes (particularly VH1-69), especially in Abs bearing long CDR-H3s. Conclusions and Significance: The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and VH1-69 gene usage may be preferentially selected during persistent infection.
-
Systemic lupus erythematosus an Autoimmune Disease of b cell hyperactivity
Nature Immunology, 2001Co-Authors: Peter E LipskyAbstract:B cells can regulate many aspects of immune reactivity, as well as differentiate into antibody-producing cells. In SLE, a Systemic Autoimmune Disease, recent research suggests enhanced B cell function is the defining pathogenic event.
Howard W Francis - One of the best experts on this subject based on the ideXlab platform.
-
spectrum of immune mediated inner ear Disease and cochlear implant results
Laryngoscope, 2012Co-Authors: Mohammad U Malik, Vinciya Pandian, Hamid Masood, David A Diaz, Voss Varela, Alfredo Jose Davalosbalderas, Martha Parracardenas, Howard W FrancisAbstract:Objectives/Hypothesis: To characterize the progression of hearing loss in patients with immune-mediated inner ear Disease (IMIED), and to identify Disease- and patient-specific factors associated with cochlear implant (CI) performance. Study Design: Retrospective cohort study. Methods: Subjects consisted of CI patients suspected to have lost their hearing due to IMIED. The primary dependent variable for functional decline was time to deafness, whereas for CI benefit it was post-CI speech perception scores. Independent variables included presence or absence of Systemic Autoimmune Disease, age at CI, and insertion depth of the cochlear electrode. Results: A transient favorable response to immunosuppressive therapy was reported in 16 of 26 patients (66.67%). The time to deafness differed between an organ (ear)-specific immune-mediated group, a Systemic immune-mediated group including Cogan syndrome and relapsing polychondritis (subgroup A), and a Systemic immune-mediated group associated with other Autoimmune Diseases (subgroup B; P = .001). Disease group (−15.52; P = .04), insertion depth of the CI electrode (40.71; P = .01), and the age at CI (−0.48, P = .05) were associated with speech perception results. Conclusions: Triaging IMIED cases based on presence and type of Systemic Autoimmune Disease may aid in selecting a management strategy. Knowledge about the predictors of CI outcome will help clinicians select appropriate patients for CIs. In the setting of significant and irreversible hearing deficit, the restoration of hearing using a cochlear prosthesis may be appropriate earlier rather than later.
Harvey Cantor - One of the best experts on this subject based on the ideXlab platform.
-
polyclonal b cell activation by the eta 1 cytokine and the development of Systemic Autoimmune Disease
Journal of Immunology, 1991Co-Authors: M A Lampe, Roberto Patarca, M V Iregui, Harvey CantorAbstract:Studies of Systemic Autoimmune Disease have led to the view that initiation and progression of the Disease process reflects chronic and sustained B cell activation by unidentified polyclonal activating agents. In earlier studies, we found that T cells from MRL/1 mice, which develop murine lupus, express very high levels of a newly defined T cell cytokine, Eta-1. Inasmuch as chronic and sustained B cell stimulation by T cells is a cardinal feature of MRL/1 Disease, we determined the effects of this cytokine on Ig production by B cells. We show that both recombinant and biochemically purified natural Eta-1 stimulate IgM and IgG production by mixtures of B cells and macrophages from the Autoimmune MRL/l strain. Additional studies suggest that optimal Ig production by Eta-1 may require macrophages and reflect enhanced Ig production by large B cells. These findings support the view that elevated levels of endogenous Eta-1 may cause chronic and sustained polyclonal B cell activation that leads to Autoimmune Disease in this murine model.
