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https://www.readbyqxmd.com/read/28077518/th17-cytokine-responses-in-lyme-disease-correlate-with-borreliaburgdorferi-antibodies-during-early-infection-in-patients-with-erythema-migrans-and-with-autoantibodies-late-in-the-illness-in-patients-with-antibiotic-refractory-lyme-arthritis
#1
Klemen Strle, Katherine B Sulka, Annalisa Pianta, Jameson T Crowley, Sheila L Arvikar, Anthony Anselmo, Ruslan Sadreyev, Allen C Steere
BACKGROUND: Control of Lyme disease is attributed predominantly to innate and adaptive TH1 immune responses, whereas the role of TH17 responses is less clear. Here we characterized these inflammatory responses in patients with erythema migrans (EM) or Lyme arthritis (LA) to elucidate their role early and late in the infection. METHODS: Levels of 21 cytokines and chemokines, representative of innate, TH1, and TH17 immune responses, were assessed by Luminex in acute and convalescent sera from 91 EM patients, in serum and synovial fluid from 141 LA patients, and in serum from 57 healthy subjects...
January 11, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28074593/microtubule-associated-protein-map-1b-novel-paraneoplastic-biomarker-running-head-map-1b-igg-novel-paraneoplastic-biomarker
#2
Avi Gadoth, Thomas J Kryzer, Jim Fryer, Andrew McKeon, Vanda A Lennon, Sean J Pittock
To report the identification of microtubule associated protein (MAP)1B as the antigen of the previously described PCA-2 antibody, its frequency and clinical, oncological and serological associations. Methods Archival serum or cerebrospinal fluid (CSF) specimens were available from 96 of 118 consecutive PCA-2-IgG-seropositive patients identified 1993-2016. The autoantigen, defined in mouse brain lysate by western blot and mass spectrometry, was confirmed by dual immunohistochemical staining using commercial antibodies...
January 11, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28066981/disruption-of-transplant-tolerance-by-an-incognito-form-of-cd8-t-cell-dependent-memory
#3
M K Nelsen, K S Beard, R J Plenter, R M Kedl, E T Clambey, R G Gill
Several approaches successfully achieve allograft tolerance in preclinical models but are challenging to translate into clinical practice. Many clinically relevant factors can attenuate allograft tolerance induction including intrinsic genetic resistance, peri-transplant infection, inflammation, and pre-existing anti-donor immunity. The prevailing view for immune memory as a tolerance barrier is that the host harbors memory cells that spontaneously cross-react to donor MHC antigens. Such pre-existing 'heterologous' memory cells have direct reactivity to donor cells and resist most tolerance regimens...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28065518/membranous-nephropathy-integrating-basic-science-into-improved-clinical-management
#4
REVIEW
Daniel C Cattran, Paul E Brenchley
Idiopathic membranous nephropathy (INM) remains a common cause of the nephrotic syndrome in adults. The autoimmune nature of IMN was clearly delineated in 2009 with the identification of the glomerular-deposited IgG to be a podocyte receptor, phospholipase A2 receptor (PLA2R) in 70% to 75% of cases. This anti-PLA2R autoantibody, predominantly the IgG4 subclass, has been quantitated in serum using an enzyme-linked immunosorbent assay and has been used to aid diagnosis and monitor response to immunosuppressive therapy...
January 5, 2017: Kidney International
https://www.readbyqxmd.com/read/28062719/characteristics-in-limbic-encephalitis-with-anti-adenylate-kinase-5-autoantibodies
#5
Le-Duy Do, Eve Chanson, Virginie Desestret, Bastien Joubert, François Ducray, Sabine Brugière, Yohann Couté, Maité Formaglio, Veronique Rogemond, Catherine Thomas-Antérion, Laura Borrega, Brice Laurens, Francois Tison, Jonathan Curot, Thomas De Brouker, Christine Lebrun-Frenay, Jean-Yves Delattre, Jean-Christophe Antoine, Jerome Honnorat
OBJECTIVE: To report 10 patients with limbic encephalitis (LE) and adenylate kinase 5 autoantibodies (AK5-Abs). METHODS: We conducted a retrospective study in a cohort of 50 patients with LE with uncharacterized autoantibodies and identified a specific target using immunohistochemistry, Western blotting, immunoprecipitation, mass spectrometry, and cell-based assay. RESULTS: AK5 (a known autoantigen of LE) was identified as the target of antibodies in the CSFs and sera of 10 patients with LE (median age 64 years; range 57-80), which was characterized by subacute anterograde amnesia without seizure and sometimes preceded by a prodromal phase of asthenia or mood disturbances...
January 6, 2017: Neurology
https://www.readbyqxmd.com/read/28043135/screening-immunomodulators-to-skew-the-antigen-specific-autoimmune-response
#6
Laura Northrup, Bradley P Sullivan, Brittany L Hartwell, Aaron Garza, Cory Berkland
Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28040323/environmental-factor-and-inflammation-driven-alteration-of-the-total-peripheral-t-cell-compartment-in-granulomatosis-with-polyangiitis
#7
Anja Kerstein, Silke Schüler, Otávio Cabral-Marques, Juliane Fazio, Robert Häsler, Antje Müller, Silke Pitann, Frank Moosig, Sebastian Klapa, Christian Haas, Dieter Kabelitz, Gabriela Riemekasten, Steffen Wolters, Peter Lamprecht
Autoimmune diseases are initiated by a combination of predisposing genetic and environmental factors resulting in self-perpetuating chronic inflammation and tissue damage. Autoantibody production and an imbalance of effector and regulatory T-cells are hallmarks of autoimmune dysregulation. While expansion of circulating effector memory T-cells is linked to disease pathogenesis and progression, the causes driving alterations of the peripheral T-cell compartment have remained poorly understood so far. In granulomatosis with polyangiitis (GPA), a prototypical autoimmune disorder of unknown aetiology, we performed for the first time a combined approach using phenotyping, transcriptome and functional analyses of T-cell populations to evaluate triggers of memory T-cell expansion...
December 28, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28029744/high-titer-rheumatoid-arthritis-antibodies-preferentially-bind-fibrinogen-citrullinated-by-peptidyl-arginine-deiminase-4
#8
Nathalie E Blachère, Salina Parveen, Mayu O Frank, Brian D Dill, Henrik Molina, Dana E Orange
OBJECTIVE: Most patients with rheumatoid arthritis (RA) harbor antibodies to citrullinated autoantigens, such as citrullinated fibrinogen. Two isoforms of peptidyl arginine deiminase (PAD), PAD2 and PAD4, which catalyze citrullination with different substrate specificities, can be detected in RA synovium. This study was undertaken to determine whether RA patient antibodies preferentially bind PAD2 or PAD4 citrullinated fibrinogen. METHODS: RA patient and normal donor plasma was tested for binding to PAD2 or PAD4 citrullinated fibrinogen, native fibrinogen, or citrullinated fibrinogen peptides in various dilutions by ELISA and Western blot...
December 28, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28011088/nitration-of-mog-diminishes-its-encephalitogenicity-depending-on-mhc-haplotype
#9
Andreas Warnecke, Sravani Musunuri, Marie N'diaye, Tatyana Sandalova, Adnane Achour, Jonas Bergquist, Robert A Harris
Post-translational modifications of autoantigens are hypothesized to affect their immunogenicity. We here report that nitration of tyrosine 40 in Myelin Oligodendrocyte Glycoprotein (MOG) abrogates its encephalitogenicity both at protein and peptide levels in the experimental autoimmune encephalomyelitis (EAE) model in H2(b) C57BL/6 mice. Furthermore, nitrated MOG displays inferior antigen-specific proliferation of 2D2 splenocytes in vitro. Conversely, H2(q) DBA1 mice remain fully susceptible to EAE induction using nitrated MOG as the dominant epitope of H2(q) mice is unaltered...
November 26, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28010761/research-techniques-made-simple-mouse-models-of%C3%A2-autoimmune-blistering-diseases
#10
Robert Pollmann, Rüdiger Eming
Autoimmune blistering diseases are examples of autoantibody-mediated, organ-specific autoimmune disorders. Based on a genetic susceptibility, such as a strong HLA-class II association, as yet unknown triggering factors induce the formation of circulating and tissue-bound autoantibodies that are mainly directed against adhesion structures of the skin and mucous membranes. Compared with other autoimmune diseases, especially systemic disorders, the pathogenicity of autoimmune blistering diseases is relatively well described...
January 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27997253/the-progress-and-potential-of-proteomic-biomarkers-for-type-1-diabetes-in-children
#11
Robert Moulder, Santosh Dilip Bhosale, Riitta Lahesmaa, David Robinson Goodlett
Although it is possible to identify the genetic risk for type 1 diabetes (T1D), it is not possible to predict who will develop the disease. New biomarkers are needed that would help understand the mechanisms of disease onset and when to administer targeted therapies and interventions. Areas covered: An overview is presented of international study efforts towards understanding the cause of T1D, including the collection of several extensive temporal sample series that follow the development of T1D in at risk children...
January 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/27989757/retinal-pigment-epithelium-and-microglia-express-the-cd5-antigen-like-protein-a-novel-autoantigen-in-age-related-macular-degeneration
#12
Alessandro Iannaccone, T J Hollingsworth, Diwa Koirala, David D New, Nataliya I Lenchik, Sarka Beranova-Giorgianni, Ivan C Gerling, Marko Z Radic, Francesco Giorgianni
We report on a novel autoantigen expressed in human macular tissues, identified following an initial Western blot (WB)-based screening of sera from subjects with age-related macular degeneration (AMD) for circulating auto-antibodies (AAbs) recognizing macular antigens. Immunoprecipitation, 2D-gel electrophoresis (2D-GE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), direct enzyme-linked immunosorbent assays (ELISA), WBs, immunohistochemistry (IHC), human primary and ARPE-19 immortalized cell cultures were used to characterize this novel antigen...
December 15, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27986906/shedding-new-light-on-the-process-of-licensing-for-pathogenicity-by-th-lymphocytes
#13
Cuiyan Tan, Wambui S Wandu, R Steven Lee, Samuel H Hinshaw, Dennis M Klinman, Eric Wawrousek, Igal Gery
Th cells sensitized against autoantigens acquire pathogenicity following two sequential events, namely activation by their target Ag and a process named "licensing." In this study, we analyzed these processes in a transgenic mouse system in which TCR-transgenic Th cells specific to hen egg lysozyme (HEL) are adoptively transferred to recipients and induce inflammation in eyes expressing HEL. Our data show that the notion that the lung is the organ where "licensing" for pathogenicity takes place is based on biased data collected with cells injected i...
December 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27974851/mechanisms-leading-from-systemic-autoimmunity-to-joint-specific-disease-in-rheumatoid-arthritis
#14
REVIEW
Anca I Catrina, Camilla I Svensson, Vivianne Malmström, Georg Schett, Lars Klareskog
A key unanswered question in the pathophysiology of rheumatoid arthritis (RA) is how systemic autoimmunity progresses to joint-specific inflammation. In patients with seropositive RA (that is, characterized by the presence of autoantibodies) evidence is accumulating that immunity against post-translationally modified (such as citrullinated) autoantigens might be triggered in mucosal organs, such as the lung, long before the first signs of inflammation are seen in the joints. However, the mechanism by which systemic autoimmunity specifically homes to the joint and bone compartment, thereby triggering inflammation, remains elusive...
December 15, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27974664/aggregatibacter-actinomycetemcomitans-induced-hypercitrullination-links-periodontal-infection-to-autoimmunity-in-rheumatoid-arthritis
#15
Maximilian F Konig, Loreto Abusleme, Jesper Reinholdt, Robert J Palmer, Ricardo P Teles, Kevon Sampson, Antony Rosen, Peter A Nigrovic, Jeremy Sokolove, Jon T Giles, Niki M Moutsopoulos, Felipe Andrade
A bacterial etiology of rheumatoid arthritis (RA) has been suspected since the beginnings of modern germ theory. Recent studies implicate mucosal surfaces as sites of disease initiation. The common occurrence of periodontal dysbiosis in RA suggests that oral pathogens may trigger the production of disease-specific autoantibodies and arthritis in susceptible individuals. We used mass spectrometry to define the microbial composition and antigenic repertoire of gingival crevicular fluid in patients with periodontal disease and healthy controls...
December 14, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27974250/the-influence-of-genetic-predisposition-and-autoimmune-hepatitis-inducing-antigens-in-disease-development
#16
Matthias Hardtke-Wolenski, Janine Dywicki, Katja Fischer, Martin Hapke, Maren Sievers, Jerome Schlue, Mark S Anderson, Richard Taubert, Fatih Noyan, Michael P Manns, Elmar Jäckel
: Autoimmune hepatitis (AIH) is defined as a chronic liver inflammation with loss of tolerance against hepatocytes. The etiology and pathophysiology of AIH are still poorly understood because reliable animal models are limited. Therefore, we recently introduced a model of experimental murine AIH by a self-limited adenoviral infection with the AIH type 2 antigen formiminotransferase cyclodeaminase (FTCD). We could demonstrate that break of humoral tolerance towards liver specific autoantigens like FTCD and cytochrome P450 2D6 (CYP2D6) is not dependent on the genetic background...
December 11, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27957508/neurochondrin-is-a-neuronal-target-antigen-in-autoimmune-cerebellar-degeneration
#17
Ramona Miske, Catharina C Gross, Madeleine Scharf, Kristin S Golombeck, Marvin Hartwig, Urvashi Bhatia, Andreas Schulte-Mecklenbeck, Kathrin Bönte, Christine Strippel, Ludger Schöls, Matthis Synofzik, Hubertus Lohmann, Inga Madeleine Dettmann, Michael Deppe, Swantje Mindorf, Tobias Warnecke, Yvonne Denno, Bianca Teegen, Christian Probst, Stefanie Brakopp, Klaus-Peter Wandinger, Heinz Wiendl, Winfried Stöcker, Sven G Meuth, Lars Komorowski, Nico Melzer
OBJECTIVE: To report on a novel neuronal target antigen in 3 patients with autoimmune cerebellar degeneration. METHODS: Three patients with subacute to chronic cerebellar ataxia and controls underwent detailed clinical and neuropsychological assessment together with quantitative high-resolution structural MRI. Sera and CSF were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IFA) and immunoblot. Immunoprecipitation with lysates of hippocampus and cerebellum combined with mass spectrometric analysis was used to identify the autoantigen, which was verified by recombinant expression in HEK293 cells and use in several immunoassays...
January 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27943421/trim21-is-important-in-the-early-phase-of-inflammation-in-the-imiquimod-induced-psoriasis-like-skin-inflammation-mouse-model
#18
Hanne Vinter, Ane Langkilde, V Ottosson, Alexander Espinosa, M Wahren-Herlenius, Line Raaby, Claus Johansen, Lars Iversen
Tripartite motif-containing protein 21 (TRIM21) regulates pro-inflammatory cytokines and type I interferons and acts as an autoantigen in certain autoimmune diseases, but TRIM21 has not been investigated in psoriasis. It has been suggested that TRIM21 may have a dual function; In the early phase of inflammation, it may function as a stimulator; but upon immune stimulation, its ubiquitinating mode of action may shift from stabilization to degradation of IRF3 causing inhibition of the immune responses. The imiquimod (IMQ)-induced psoriasis-like mouse model displays features similar to those of human psoriasis...
December 11, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27943257/a-clinical-and-serological-study-of-linear-iga-bullous-dermatosis-without-linear-immunoglobulin-deposition-other-than-iga-at-the-basement-membrane-zone-in-direct-immunofluorescence
#19
C Ohata, N Ishii, H Koga, T Nakama
BACKGROUND: Linear IgA bullous dermatosis (LABD) is a heterogeneous disease. Different diagnostic criteria have been used in different reports. OBJECTIVES: We aimed to reappraise the characteristic features of LABD with only IgA deposition at the basement membrane zone (BMZ) in direct immunofluorescence (DIF). METHODS: We retrospectively collected 101 patients who had a) blisters on the skin and/or mucous membrane, b) subepidermal blisters in a biopsy specimen, and c) linear IgA deposition along BMZ with/without linear C3 deposition at the BMZ in DIF from our archival records from January 1, 1996, through December 31, 2014...
December 11, 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/27940915/tolerance-checkpoint-bypass-permits-emergence-of-pathogenic-t-cells-to-neuromyelitis-optica-autoantigen-aquaporin-4
#20
Sharon A Sagan, Ryan C Winger, Andrés Cruz-Herranz, Patricia A Nelson, Sarah Hagberg, Corey N Miller, Collin M Spencer, Peggy P Ho, Jeffrey L Bennett, Michael Levy, Marc H Levin, Alan S Verkman, Lawrence Steinman, Ari J Green, Mark S Anderson, Raymond A Sobel, Scott S Zamvil
Aquaporin-4 (AQP4)-specific T cells are expanded in neuromyelitis optica (NMO) patients and exhibit Th17 polarization. However, their pathogenic role in CNS autoimmune inflammatory disease is unclear. Although multiple AQP4 T-cell epitopes have been identified in WT C57BL/6 mice, we observed that neither immunization with those determinants nor transfer of donor T cells targeting them caused CNS autoimmune disease in recipient mice. In contrast, robust proliferation was observed following immunization of AQP4-deficient (AQP4(-/-)) mice with AQP4 peptide (p) 135-153 or p201-220, peptides predicted to contain I-A(b)-restricted T-cell epitopes but not identified in WT mice...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
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