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Journal of Autoimmunity

Andrea Fava, Michelle Petri
Systemic lupus erythematosus (SLE) is a worldwide chronic autoimmune disease which may affect every organ and tissue. Genetic predisposition, environmental triggers, and the hormonal milieu, interplay in disease development and activity. Clinical manifestations and the pattern of organ involvement are widely heterogenous, reflecting the complex mosaic of disrupted molecular pathways converging into the SLE clinical phenotype. The SLE complex pathogenesis involves multiple cellular components of the innate and immune systems, presence of autoantibodies and immunocomplexes, engagement of the complement system, dysregulation of several cytokines including type I interferons, and disruption of the clearance of nucleic acids after cell death...
November 15, 2018: Journal of Autoimmunity
Laurence B Peterson, Charles J M Bell, Sarah K Howlett, Marcin L Pekalski, Kevin Brady, Heather Hinton, Denise Sauter, John A Todd, Pablo Umana, Oliver Ast, Inja Waldhauer, Anne Freimoser-Grundschober, Ekkehard Moessner, Christian Klein, Ralf J Hosse, Linda S Wicker
Susceptibility to multiple autoimmune diseases is associated with common gene polymorphisms influencing IL-2 signaling and Treg function, making Treg -specific expansion by IL-2 a compelling therapeutic approach to treatment. As an in vivo IL-2 half-life enhancer we used a non-targeted, effector-function-silent human IgG1 as a fusion protein. An IL-2 mutein (N88D) with reduced binding to the intermediate affinity IL-2Rβγ receptor was engineered with a stoichiometry of two IL-2N88D molecules per IgG, i.e. IgG-(IL-2N88D)2 ...
November 13, 2018: Journal of Autoimmunity
Laura Cristoferi, Alessandra Nardi, Vincenzo Ronca, Pietro Invernizzi, George Mells, Marco Carbone
Risk prediction modelling is important to better understand the determinants of the course and outcome of PBC and to inform the risk across the disease continuum in PBC enabling risk-stratified follow-up care and personalised therapy. Current prognostic models in PBC are based on treatment response to ursodeoxycholic acid because of the well-established relationship between alkaline phosphatase on treatment and long-term outcome. In addition, serum alkaline phosphatase correlates with ductular reaction and biliary metaplasia, which are hallmark of biliary injury...
November 9, 2018: Journal of Autoimmunity
Peter Lamprecht, Nicole Fischer, Jiabin Huang, Lia Burkhardt, Marc Lütgehetmann, Fabian Arndt, Ida Rolfs, Anja Kerstein, Christof Iking-Konert, Martin Laudien
Dysbiosis¸ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of many chronic inflammatory and autoimmune diseases. To assess the composition of the microbial upper respiratory tract (URT) community in patients with granulomatosis with polyangiitis (GPA), we used culture-independent high-throughput methods. In this prospective clinical study, nasal swabs were collected from patients with GPA, patients with rheumatoid arthritis (RA, disease control), and healthy controls...
November 9, 2018: Journal of Autoimmunity
Taco A van der Meulen, Hermie J M Harmsen, Arnau Vich Vila, Alexander Kurilshikov, Silvia C Liefers, Alexandra Zhernakova, Jingyuan Fu, Cisca Wijmenga, Rinse K Weersma, Karina de Leeuw, Hendrika Bootsma, Fred K L Spijkervet, Arjan Vissink, Frans G M Kroese
OBJECTIVE: Alterations in the microbiota composition of the gastro-intestinal tract are suspected to be involved in the etiopathogenesis of two closely related systemic inflammatory autoimmune diseases: primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). Our objective was to assess whether alterations in gut and oral microbiota compositions are specific for pSS and SLE. METHODS: 16S ribosomal RNA gene sequencing was performed on fecal samples from 39 pSS patients, 30 SLE patients and 965 individuals from the general population, as well as on buccal swab and oral washing samples from the same pSS and SLE patients...
November 9, 2018: Journal of Autoimmunity
Melissa A Cunningham, Mara Lennard Richard, Jena R Wirth, Jennifer L Scott, Jackie Eudaly, Phil Ruiz, Gary S Gilkeson
Female sex is a risk factor for lupus. Sex hormones, sex chromosomes and hormone receptors are implicated in the pathogenic pathways in lupus. Estrogen receptor alpha (ERα) knockout (KO) mice are used for defining hormone receptor effects in lupus. Prior studies of ERα KO in lupus have conflicting results, likely due to sex hormone levels, different lupus strains and different ERα KO constructs. Our objective was to compare a complete KO of ERα vs. the original functional KO of ERα (expressing a short ERα) on disease expression and immune phenotype, while controlling sex hormone levels...
November 8, 2018: Journal of Autoimmunity
Richard Taubert, Katharina Luise Hupa-Breier, Elmar Jaeckel, Michael P Manns
Autoimmune hepatitis (AIH) is an orphan disease characterized by an autoimmune attack against hepatocytes. The exact sequence of events that leads to a breach of tolerance is incompletely understood. Current hypotheses suggest that environmental agents such as toxins or infectious agents like viruses cause a tissue damage that initiates autoimmunity in genetically susceptible individuals. The growing knowledge of the multi-facetted immune dysregulation, which involves Th1/Th17 polarization and the suspected inability of regulatory T cells to revert autoimmunity in the otherwise tolerogenic milieu of the liver, offers multiple new therapeutic approaches and targets...
November 3, 2018: Journal of Autoimmunity
Nanda Kerkar, Diego Vergani
De novo autoimmune hepatitis (AIH) is an unusual cause of graft dysfunction after liver transplantation. This entity was originally described in 1996 in children transplanted for conditions other than AIH, who developed biochemical and histological features similar to AIH and responded to the therapy of classical AIH with steroids and azathioprine. In the last two decades, there have been reports of occurrence of de novo AIH in pediatric and adult liver transplant recipients, in the latter often being given different nomenclature including 'plasma cell hepatitis'...
November 2, 2018: Journal of Autoimmunity
Colleen S Curran, Sarthak Gupta, Ignacio Sanz, Elad Sharon
Programmed death (PD)-1 receptors and their ligands have been identified in the pathogenesis and development of systemic lupus erythematosus (SLE). Two key pathways, toll-like receptor and type I interferon, are significant to SLE pathogenesis and modulate the expression of PD-1 and the ligands (PD-L1, PD-L2) through activation of NF-κB and/or STAT1. These cell signals are regulated by tyrosine kinase (Tyro, Axl, Mer) receptors (TAMs) that are aberrantly activated in SLE. STAT1 and NF-κB also exhibit crosstalk with the aryl hydrocarbon receptor (AHR)...
November 2, 2018: Journal of Autoimmunity
Thomas Lung, Lorenz Risch, Martin Risch, Benjamin Sakem, Reinhard Würzner, Urs Nydegger
The multi-tasking organ liver, which is the major synthesis site of most serum proteins, supplies humoral components of the innate, - including proteins of the complement system; and, less intensely, also of the acquired immune system. In addition to hepatocyte origins, C1q, factor D, C3, C7 and other protein components of the complement system are produced at various body locations by monocytes/macrophages, lymphocytes, adipocytes, endometrium, enterocytes, keratinocytes and epithelial cells; but the contribution of these alternate sites to the total serum concentrations is slight...
October 31, 2018: Journal of Autoimmunity
Sam Kara, Gerardo A Pirela-Morillo, Conrad T Gilliam, George D Wilson
Convergent evidence from multiple and independent genetics studies implicate a small number of genes that predispose individuals to multiple autoimmune disorders (AuD). These intersecting loci reinforced the hypothesis that disorders with overlapping etiology group into a cluster of closely related genes within a whole genome molecular interaction network. We tested the hypothesis that "biological network proximity" within a whole genome molecular interaction network can be used to inform the search for multigene inheritance...
October 31, 2018: Journal of Autoimmunity
Juan Cortés, Jorge Hidalgo, Sergio Aguilera, Isabel Castro, Mónica Brito, Hery Urra, Paola Pérez, María-José Barrera, Patricia Carvajal, Ulises Urzúa, Sergio González, Claudio Molina, Verónica Bahamondes, Marcela Hermoso, María-Julieta González
Sjögren's syndrome (SS) is an autoimmune exocrinopathy associated with severe secretory alterations by disruption of the glandular architecture integrity, which is fundamental for a correct function and localization of the secretory machinery. Syt-1, PI(4,5)P2 and Ca2+ are significant factors controlling exocytosis in different secretory cells, the Ca2+ role being the most studied. Salivary acinar cells from SS-patients show a defective agonist-regulated intracellular Ca2+ release together with a decreased IP3R expression level, and this condition may explain a reduced water release...
October 31, 2018: Journal of Autoimmunity
Laurie Baert, Benoit Manfroi, Olivier Casez, Nathalie Sturm, Bertrand Huard
Autoimmunity occurs when an adaptive immune response is directed against a self-antigen. As such, autoimmune reactions associated with the production of autoantibodies are common. These autoantibodies may either be pathogenic by inducing the initial damage to self, or exacerbate the reaction secondarily to the initial damage. In both cases, the pathway(s) leading to exposure of the immune system to the self-antigen inducing the production of autoantibodies is largely unknown. The latter is largely complicating the setting of putative prophylactic treatments...
October 30, 2018: Journal of Autoimmunity
Annarosa Floreani, Paula Restrepo-Jiménez, Maria Francesca Secchi, Sara De Martin, Patrick S C Leung, Edward Krawitt, Christopher L Bowlus, M Eric Gershwin, Juan-Manuel Anaya
Autoimmune hepatitis is a chronic inflammatory liver disease characterized by hypergammaglobulinemia, the presence of autoantibodies, and inflammation within the liver, including lymphocytic infiltrates and interface hepatitis. Autoimmune hepatitis shows a female predominance and can present at any age and in any ethnicity. The disease is thought to be a consequence of a break of immune tolerance leading to an autoimmune process that induces liver injury. The self-attack is triggered by T-helper cell-mediated liver autoantigen recognition and B-cell production of autoantibodies, and is sustained by impaired regulatory T cells number and function...
October 29, 2018: Journal of Autoimmunity
Chen Huang, Xuemei Li, Jinghua Wu, Wei Zhang, Shiren Sun, Liya Lin, Xie Wang, Hongmei Li, Xiaolei Wu, Peng Zhang, Guoshuang Xu, Hanmin Wang, Hongbao Liu, Yuzhen Liu, Dapeng Chen, Li Zhuo, Wenge Li, Huanming Yang, Jian Wang, Ling Wang, Xiao Liu
Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. The pathologic hallmark of IgAN is immune complex deposited in glomerular mesangium, which induces inflammation and affects the kidney's normal functions. The exact pathogenesis of IgAN, however, remains obscure. Further, in current clinical practice, the diagnosis relies on needle biopsy of renal tissue. Therefore, a non-invasive method for diagnosis and prognosis surveillance of the disease is highly desirable. To this end, we investigated the T cell receptor beta chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire in circulating lymphocytes and compared them with kidney infiltrating lymphocytes using immune repertoire high throughput sequencing...
October 29, 2018: Journal of Autoimmunity
Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani, Diego Vergani
Autoimmune serology is key to the diagnosis and management of autoimmune liver diseases. Its correct use in clinical practice requires a basic knowledge of the laboratory techniques used for autoantibody detection. Indirect immunofluorescence (IIF) on triple rodent tissue is still the gold standard screening procedure for liver-relevant autoantibodies, while HEp2 cells and human ethanol-fixed neutrophils are used as substrates to characterize nuclear reactivities and to detect anti-neutrophil cytoplasm antibody, respectively...
October 23, 2018: Journal of Autoimmunity
Benedetta Terziroli Beretta-Piccoli, Diego Vergani, Giorgina Mieli-Vergani
Juvenile sclerosing cholangitis is a rare chronic hepatobiliary disorder characterized by inflammation of the intra- and/or extrahepatic bile ducts, bile duct dilatation, narrowing and obliteration, and, histologically, by inflammatory bile duct damage leading to periductular fibrosis. The diagnosis is based on endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. In children, it may be associated to a variety of systemic and hepatic conditions: thus, the term "primary" sclerosing cholangitis should be reserved for the rare cases without a known cause...
October 23, 2018: Journal of Autoimmunity
Yannick Kronimus, Richard Dodel, Sebastian P Galuska, Sascha Neumann
Immunoglobulin G (IgG) is the most abundant antibody subclass of the human circulatory system and has important functions in the adaptive immune response. On the one hand, recognition and neutralization of antigens is mediated by the fab fragment, and on the other hand, processes such as phagocytosis, complement activation and inflammatory reactions are triggered by the Fc fragment. Here, the composition of conserved N-glycans attached to asparagine 297 of the IgG CH2 domain is a major critical factor that particularly modulates the effector functions of IgG...
October 22, 2018: Journal of Autoimmunity
Christiane Sokollik, Valerie A McLin, Diego Vergani, Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani
Autoimmune hepatitis (AIH) is a rare, chronic disease that affects both adults and children, including infants. The disease is probably triggered by environmental factors in genetically predisposed individuals. The clinical presentation ranges from asymptomatic patients or patients with non-specific symptoms, such as fatigue, to fulminant liver failure, many children presenting with symptoms indistinguishable from those of acute hepatitis. Raised transaminase and immunoglobulin G (IgG) levels, in association with circulating autoantibodies, guide towards the diagnosis...
October 19, 2018: Journal of Autoimmunity
Christian Lundtoft, Julia Seyfarth, Sonja Oberstrass, Joachim Rosenbauer, Christina Baechle, Michael Roden, Reinhard W Holl, Ertan Mayatepek, Sebastian Kummer, Thomas Meissner, Marc Jacobsen
Interleukin-7 receptor α-chain (IL7RA) haplotypes are associated with susceptibility to autoimmune diseases including type 1 diabetes (T1D). Previous studies found lower soluble IL-7Rα (sIL-7Rα) serum levels of the protection-associated IL7RA haplotype assumed to reduce IL-7 availability for self-reactive T cells. Also, a risk-associated IL7RA haplotype is accompanied by lower sIL-7Rα serum concentrations but no underlying mechanisms have been described and the causative polymorphism remains unknown. Here, we characterized functional implications of the nonsynonymous rs1494558 (Thr66Ile), which tags the protection-associated IL7RA haplotype, in HEK293T cells and serum samples of T1D patients with different haplotype carriers...
October 17, 2018: Journal of Autoimmunity
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