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Journal of Autoimmunity

Giovanna Restuccia, Luigi Boiardi, Alberto Cavazza, Mariagrazia Catanoso, Pierluigi Macchioni, Francesco Muratore, Alessandra Soriano, Luca Cimino, Raffaella Aldigeri, Filippo Crescentini, Nicolò Pipitone, Carlo Salvarani
OBJECTIVE: To evaluate the frequency of long-term remission after glucocorticoids (GCs) suspension in an Italian cohort of patients with biopsy-proven GCA and to identify factors that may predict long-term remission. METHODS: We evaluated 131 patients with biopsy-proven transmural GCA diagnosed and followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 18 months of follow-up...
October 11, 2016: Journal of Autoimmunity
Caitlin M Gillis, Priscila P Zenatti, David A Mancardi, Héloïse Beutier, Laurence Fiette, Lynn E Macdonald, Andrew J Murphy, Susanna Celli, Philippe Bousso, Friederike Jönsson, Pierre Bruhns
Two activating mouse IgG receptors (FcγRs) have the ability to bind monomeric IgG, the high-affinity mouse FcγRI and FcγRIV. Despite high circulating levels of IgG, reports using FcγRI(-/-) or FcγRIV(-/-) mice or FcγRIV-blocking antibodies implicate these receptors in IgG-induced disease severity or therapeutic Ab efficacy. From these studies, however, one cannot conclude on the effector capabilities of a given receptor, because different activating FcγRs possess redundant properties in vivo, and cooperation between FcγRs may occur, or priming phenomena...
October 10, 2016: Journal of Autoimmunity
Chantal Kuhn, Rafael M Rezende, Andre Pires da Cunha, Fabrice Valette, Francisco J Quintana, Lucienne Chatenoud, Howard L Weiner
CD3-specific monoclonal antibody (mAb) treats autoimmune disease in animal models and has shown promise in clinical trials of type 1 diabetes. Whereas intravenous administration of CD3-specific mAb acts primarily by transient depletion of activated effector T cells, oral CD3-specific mAb acts primarily by the induction Tregs. We investigated whether oral CD3-specific mAb inhibits disease in non obese diabetic (NOD) mice that spontaneously develop autoimmune diabetes, closely resembling human type 1 diabetes...
October 10, 2016: Journal of Autoimmunity
Magdalena Paterka, Jan Oliver Voss, Johannes Werr, Eva Reuter, Sophia Franck, Tina Leuenberger, Josephine Herz, Helena Radbruch, Tobias Bopp, Volker Siffrin, Frauke Zipp
Counter-balancing regulatory mechanisms, such as the induction of regulatory T cells (Treg), limit the effects of autoimmune attack in neuroinflammation. However, the role of dendritic cells (DCs) as the most powerful antigen-presenting cells, which are intriguing therapeutic targets in this context, is not fully understood. Here, we demonstrate that conditional ablation of DCs during the priming phase of myelin-specific T cells in experimental autoimmune encephalomyelitis (EAE) selectively aborts inducible Treg (iTreg) induction, whereas generation of T helper (Th)1/17 cells is unaltered...
October 2, 2016: Journal of Autoimmunity
Akiko Takeuchi, Takashi Matsushita, Kenzo Kaji, Yoshinobu Okamoto, Masahide Yasui, Masayoshi Hirata, Naoto Oishi, Akira Higashi, Mariko Seishima, Tomoya Asano, Manabu Fujimoto, Masataka Kuwana, Kazuhiko Takehara, Yasuhito Hamaguchi
OBJECTIVE: To identify and characterize a novel connective tissue disease (CTD)-related autoantibody (autoAb) directed against scaffold attachment factor B (SAFB). METHODS: AutoAb specificity was analyzed using RNA and protein-immunoprecipitation assays. Autoimmune targets were affinity purified using patients' sera and subjected to liquid chromatography mass spectrometry. RESULTS: By immunoprecipitation assay, 10 sera reacted with a protein with a molecular weight of approximately 160 kDa...
September 24, 2016: Journal of Autoimmunity
Cheuk Wun Li, Roman Osman, Francesca Menconi, Erlinda S Concepcion, Yaron Tomer
Autoimmune polyglandular syndrome 3 variant (APS3v) refers to the co-occurrence of autoimmune thyroiditis (AITD) and type 1 diabetes (T1D) within the same individual. HLA class II confers the strongest susceptibility to APS3v. We previously identified a unique amino acid signature of the HLA-DR pocket (designated APS3v HLA-DR pocket) that predisposes to APS3v. We hypothesized that both thyroid and islet peptides can be presented by the unique APS3v HLA-DR pocket, triggering AITD + T1D together. To test this hypothesis we screened islet and thyroid peptides for their ability to bind to the APS3v HLA-DR pocket...
September 23, 2016: Journal of Autoimmunity
Florian Wiede, Faruk Sacirbegovic, Yew Ann Leong, Di Yu, Tony Tiganis
Non-coding single nucleotide polymorphisms that repress PTPN2 expression have been linked with the development of type 1 diabetes, rheumatoid arthritis and Crohn's disease. PTPN2 attenuates CD8(+) T cell responses to self and prevents overt autoreactivity in the context of T cell homeostasis and antigen cross-presentation. The role of PTPN2 in other immune subsets in the development of autoimmunity remains unclear. Here we show that the inducible deletion of PTPN2 in hematopoietic compartment of adult non-autoimmune prone mice results in systemic inflammation and autoimmunity...
September 19, 2016: Journal of Autoimmunity
Shuji Sumitomo, Shinichiro Nakachi, Tomohisa Okamura, Yumi Tsuchida, Rika Kato, Hirofumi Shoda, Asayo Furukawa, Nobuo Kitahara, Kenji Kondo, Tatsuya Yamasoba, Kazuhiko Yamamoto, Keishi Fujio
IL-10-producing regulatory T cells (IL-10-producing Tregs) are one of the regulatory T cell subsets characterized by the production of high amounts of IL-10, the lack of FOXP3 expression and the strong immunosuppressive capabilities. IL-10-producing Tregs have been primarily reported as induced populations thus far, in part because identifying naturally occurring IL-10-producing Tregs was difficult due to the lack of definitive surface markers. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue that we have identified as being expressed on IL-10 producing Tregs...
September 18, 2016: Journal of Autoimmunity
Fanlei Hu, Hongjiang Liu, Xu Liu, Xia Zhang, Liling Xu, Huaqun Zhu, Yingni Li, Lianjie Shi, Limin Ren, Jian Zhang, Zhanguo Li, Yuan Jia
Regulatory B10 cells were functionally impaired in rheumatoid arthritis (RA), yet the mechanisms were unclear. B cells are recently recognized as important participants in osteoclastogenesis by producing RANKL. In this study, we investigated whether regulatory B10 cells could convert into RANKL-producing cells, thus impairing their immunosuppressive functions in RA and exacerbating the disease progression. Our results showed that human regulatory B10 cells could ectopically express RANKL. Under RA circumstance, RANKL-producing B10 cells expanded dramatically, partially induced by TNF-α...
September 14, 2016: Journal of Autoimmunity
Echarki Zerif, Aida Maalem, Simon Gaudreau, Chantal Guindi, Muhammad Ramzan, Steeve Véroneau, Denis Gris, Jana Stankova, Marek Rola-Pleszczynski, Walid Mourad, Gilles Dupuis, Abdelaziz Amrani
Defects in dendritic cells (DCs) development and function lead to autoimmune disorders. Autoimmune diabetes in humans and NOD mice results from a breakdown of self-tolerance, ending in T cell-mediated β-cell destruction. DCs dysfunction in NOD mice results in part from a defect in the JAK-STAT5 signaling pathway associated with the idd4 susceptibility locus. The involvement of Stat5b in DCs tolerogenic functions remains unknown. We have generated transgenic mice (NOD.CD11c(Stat5b-CA)) expressing a constitutively active form of the Stat5b gene (Stat5b-CA) under control of CD11c promoter...
September 12, 2016: Journal of Autoimmunity
Andrea Doria, M Eric Gershwin, Carlo Selmi
The significant decrease in mortality rates worldwide, the increased proportion of patients achieving a durable remission, and the recent approval of a new drug after several decades are encouraging advances in the tangled history of systemic lupus erythematosus (SLE). However, when data are observed more closely, the research findings on disease pathogenesis and targeted treatments have been quite misleading, as illustrated by the central role of B cells but the missed endpoints in rituximab clinical trials which are burdened by the wide variability of SLE manifestations or the ethnic determinants of disease severity...
August 31, 2016: Journal of Autoimmunity
Satomi Hisamoto, Shinji Shimoda, Kenichi Harada, Sho Iwasaka, Shinya Onohara, Yong Chong, Minoru Nakamura, Yuki Bekki, Tomoharu Yoshizumi, Toru Ikegami, Yoshihiko Maehara, Xiao-Song He, M Eric Gershwin, Koichi Akashi
Understanding the mechanisms of chronic inflammation in primary biliary cholangitis (PBC) is essential for successful treatment. Earlier work has demonstrated that patients with PBC have reduced expression of the anion exchanger 2 (AE2) on biliary epithelial cells (BEC) and deletion of AE2 gene has led to a PBC-like disorder in mice. To directly address the role of AE2 in preventing PBC pathogenesis, we took advantage of our ability to isolate human BEC and autologous splenic mononuclear cells (SMC). We studied the influence of hydrophobic bile acids, in particular, glycochenodeoxycholic acid (GCDC), on AE2 expression in BEC and the subsequent impact on the phenotypes of BEC and local inflammatory responses...
August 31, 2016: Journal of Autoimmunity
Carlo Selmi, Jobert G Barin, Noel R Rose
In the broad field of autoimmunity and clinical immunology, experimental evidence over the past few years have demonstrated several connections between the immune system and the nervous system, both central and peripheral, leading to the definition of neuroimmunology and of an immune-brain axis. Indeed, the central nervous system as an immune-privileged site, thanks to the blood-brain barrier, is no longer a dogma as the barrier may be altered during chronic inflammation with disruptive changes of endothelial cells and tight junctions, largely mediated by adenosine receptors and the expression of CD39/CD73...
August 18, 2016: Journal of Autoimmunity
Olivier Herbin, Anthony J Bonito, Seihwan Jeong, Erica G Weinstein, Adeeb H Rahman, Huabao Xiong, Miriam Merad, Konstantina Alexandropoulos
In the thymus, antigen presenting cells (APCs) namely, medullary thymic epithelial cells (mTECs) and thymic dendritic cells (tDCs) regulate T cell tolerance through elimination of autoreactive T cells and production of thymic T regulatory (tTreg) cells. How the different APCs in the thymus share the burden of tolerazing the emerging T cell repertoire remains unclear. For example, while mutations that inhibit mTEC development or function associate with peripheral autoimmunity, the role of tDCs in organ-specific autoimmunity and tTreg cell production remains controversial...
August 16, 2016: Journal of Autoimmunity
Cristian Doñas, Macarena Carrasco, Macarena Fritz, Carolina Prado, Gabriela Tejón, Francisco Osorio-Barrios, Valeria Manríquez, Paz Reyes, Rodrigo Pacheco, María Rosa Bono, Alejandra Loyola, Mario Rosemblatt
As it has been established that demethylation of lysine 27 of histone H3 by the lysine-specific demethylase JMJD3 increases immune responses and thus elicits inflammation, we hypothesize that inhibition of JMJD3 may attenuate autoimmune disorders. We found that in vivo administration of GSK-J4, a selective inhibitor of JMJD3 and UTX, ameliorates the severity of experimental autoimmune encephalomyelitis (EAE). In vitro experiments revealed that the anti-inflammatory effect of GSK-J4 was exerted through an effect on dendritic cells (DCs), promoting a tolerogenic profile characterized by reduced expression of costimulatory molecules CD80/CD86, an increased expression of tolerogenic molecules CD103 and TGF-β1, and reduced secretion of proinflammatory cytokines IL-6, IFN-γ, and TNF...
August 12, 2016: Journal of Autoimmunity
Maria Teruel, Marta E Alarcón-Riquelme
The genome-wide association study is a free-hypothesis approach based on screening of thousands or even millions of genetic variants distributed throughout the whole human genome in relation to a phenotype. The relevant role of the genome-wide association studies in the last decade is undisputed because it has permitted to elucidate multiple risk genetic factors associated with the susceptibility to several human complex diseases. Regarding systemic lupus erythematosus (SLE) this approach has allowed to identify more than 60 risk loci for SLE susceptibility across populations to date, increasing our understanding on the pathogenesis of this disease...
August 10, 2016: Journal of Autoimmunity
Julie M Ward, Michelle L Ratliff, Mikhail G Dozmorov, Graham Wiley, Joel M Guthridge, Patrick M Gaffney, Judith A James, Carol F Webb
Previously, we determined that enhanced disease activity in patients with systemic lupus erythematosus (SLE) was associated with dramatic increases in numbers of B lymphocytes expressing the transcription factor ARID3a. Our data now indicate ARID3a is important for interferon alpha (IFNa) expression and show a strong association between ARID3a expression and transcription of genes associated with lupus IFN signatures. Furthermore, both ARID3a and IFNa production were elicited in healthy control B cells upon stimulation with the TLR 9 agonist, CpG...
August 10, 2016: Journal of Autoimmunity
Salyan Bhattarai, Khetam Ghannam, Sabine Krause, Olivier Benveniste, Andreas Marg, Gerjan de Bruin, Bo-Tao Xin, Hermen S Overkleeft, Simone Spuler, Werner Stenzel, Eugen Feist
Idiopathic inflammatory myopathies (IIMs) are diseases with muscle weakness, morphologically characterized by inflammatory infiltration and increased expression of MHC class I molecule on myofibers. Immunoproteasome, as a proteolytic complex that shapes the repertoire of antigenic peptides, has been previously demonstrated to be over-expressed in IIMs at mRNA level. In this study, we investigated the expression and the function of the immunoproteasome in IIMs in more detail. As shown by immunofluorescence staining, expression of relevant players of the immunoproteasome was detectable in the inflamed skeletal muscle tissue from IIM patients...
August 10, 2016: Journal of Autoimmunity
Rodrigo Liberal, Edward L Krawitt, John M Vierling, Michael P Manns, Giorgina Mieli-Vergani, Diego Vergani
Autoimmune hepatitis (AIH) is a severe liver disease affecting all age groups worldwide. Novel basic and clinical aspects of AIH, addressed at a Monothematic Conference in London in September 2015, are highlighted in this review. The diagnosis of AIH relies upon detection of characteristic autoantibodies, hypergammaglobulinemia, and interface hepatitis on liver histology. The International Autoimmune Hepatitis Group (IAIHG) has devised diagnostic scoring systems to help in comparative studies and clinical practice...
August 5, 2016: Journal of Autoimmunity
Pier Luigi Meroni
Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions...
August 2, 2016: Journal of Autoimmunity
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