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https://www.readbyqxmd.com/read/28219888/cd74-deficiency-mitigates-systemic-lupus-erythematosus-like-autoimmunity-and-pathological-findings-in-mice
#1
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Lijun Zhang, Vasileios C Kyttaris, George C Tsokos, Isaac E Stillman, Takaharu Ichimura, Joseph V Bonventre, Peter Libby, Guo-Ping Shi
CD74 mediates MHC class-II antigenic peptide loading and presentation and plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. C57BL/6 Fas(lpr) mice that develop spontaneous lupus-like autoimmunity and pathology showed elevated CD74 expression in the inflammatory cell infiltrates and the adjacent tubular epithelial cells (TECs) in kidneys affected by lupus nephritis but negligible levels in kidneys from age-matched wild-type mice. The inflammatory cytokine IFN-γ or IL-6 induced CD74 expression in kidney TECs in vitro...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28218625/egress-of-sperm-autoantigen-from-seminiferous-tubules-maintains-systemic-tolerance
#2
Kenneth S K Tung, Jessica Harakal, Hui Qiao, Claudia Rival, Jonathan C H Li, Alberta G A Paul, Karen Wheeler, Patcharin Pramoonjago, Constance M Grafer, Wei Sun, Robert D Sampson, Elissa W P Wong, Prabhakara P Reddi, Umesh S Deshmukh, Daniel M Hardy, Huanghui Tang, C Yan Cheng, Erwin Goldberg
Autoimmune responses to meiotic germ cell antigens (MGCA) that are expressed on sperm and testis occur in human infertility and after vasectomy. Many MGCA are also expressed as cancer/testis antigens (CTA) in human cancers, but the tolerance status of MGCA has not been investigated. MGCA are considered to be uniformly immunogenic and nontolerogenic, and the prevailing view posits that MGCA are sequestered behind the Sertoli cell barrier in seminiferous tubules. Here, we have shown that only some murine MGCA are sequestered...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28213757/germinal-centre-frequency-is-decreased-in-pancreatic-lymph-nodes-from-individuals-with-recent-onset-type-1-diabetes
#3
Abby Willcox, Sarah J Richardson, Lucy S K Walker, Sally C Kent, Noel G Morgan, Kathleen M Gillespie
AIMS/HYPOTHESIS: Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes. METHODS: Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1...
February 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#4
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205558/plant-based-vaccines-for-oral-delivery-of-type-1-diabetes-related-autoantigens-evaluating-oral-tolerance-mechanisms-and-disease-prevention-in-nod-mice
#5
Amanda L Posgai, Clive H Wasserfall, Kwang-Chul Kwon, Henry Daniell, Desmond A Schatz, Mark A Atkinson
Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3(+) and LAP(+) regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199852/b-cell-activating-factor-baff-selects-il-10-b-cells-over-il-10-b-cells-during-inflammatory-responses
#6
Ning Ma, Yu Zhang, Qilin Liu, Zhiding Wang, Xiaoling Liu, Gaizhi Zhu, Dandan Yu, Gencheng Han, Guojiang Chen, Chunmei Hou, Tianxiao Wang, Yuanfang Ma, Beifen Shen, Yan Li, He Xiao, Renxi Wang
B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10(-)B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10(+) Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10(+)B cells over IL-10(-)B cells under noninflammatory conditions in vitro, whereas it expanded IL-10(-)B cells over IL-10(+)B cells during inflammatory responses, such as stimulation with autoantigen and LPS...
February 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28199812/intralymphatic-injection-of-autoantigen-in-type-1-diabetes
#7
LETTER
Johnny Ludvigsson, Jeanette Wahlberg, Rosaura Casas
No abstract text is available yet for this article.
16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28192214/immune-recognition-surface-construction-of-mycobacterium-tuberculosis-epitope-specific-antibody-responses-in-tuberculosis-patients-identified-by-peptide-microarrays
#8
REVIEW
Davide Valentini, Martin Rao, Giovanni Ferrara, Marc Perkins, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Understanding of humoral immune responses in tuberculosis (TB) is gaining interest, since B-cells and antibodies may be important in diagnosis as well as protective immune responses. High-content peptide microarrays (HCPM) are highly precise and reliable for gauging specific antibody responses to pathogens, as well as autoantigens. METHODS: An HCPM comprising epitopes spanning 154 proteins of Mycobacterium tuberculosis was used to gauge specific IgG antibody responses in sera of TB patients from Africa and South America...
February 10, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28186997/autoantibodies-against-glucose-regulated-protein-78-as-serological-biomarkers-in-metastatic-and-recurrent-hepatocellular-carcinoma
#9
Xia Ying, Su-Xia Han, Chen-Chen He, Cong-Ya Zhou, Yi-Ping Dong, Meng-Jiao Cai, Xin Sui, Cheng-Xian Ma, Xiao Sun, Yuan-Yuan Zhang, Wen-Li Gou, Clifford Mason, Qing Zhu
PURPOSE: To identify Heptocellular carcinoma (HCC) associated antigens by proteomics, and validate whether autoantibodies against tumor-associated antigens (TAAs) could be used for diagnosis and conditional monitoring. RESULTS: The 78 kDa glucose regulated protein (GRP78) was selected as a candidate TAA. The titers of autoantibodies against 78 kDa glucose regulated protein (GRP78) from patients with HCC, liver cirrhosis (LC), and chronic hepatitis (CH) were significantly higher than that from normal controls (P<0...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184367/novel-immunotherapies-for-autoimmune-hepatitis
#10
REVIEW
Shamir Cassim, Marc Bilodeau, Catherine Vincent, Pascal Lapierre
Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28183721/carbamylation-of-vimentin-is-inducible-by-smoking-and-represents-an-independent-autoantigen-in-rheumatoid-arthritis
#11
Caroline Ospelt, Holger Bang, Eugen Feist, Giovanni Camici, Stephan Keller, Jacqueline Detert, Anette Krämer, Steffen Gay, Khetam Ghannam, Gerd R Burmester
OBJECTIVES: Smoking has been connected to citrullination of antigens and formation of anti-citrullinated peptide antibodies (ACPAs) in rheumatoid arthritis (RA). Since smoking can modify proteins by carbamylation (formation of homocitrulline), this study was conducted to investigate these effects on vimentin in animal models and RA. METHODS: The efficiency of enzymatic carbamylation of vimentin was characterised. B-cell response was investigated after immunisation of rabbits with different vimentin isoforms...
February 9, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28181533/ebola-virus-infection-induces-autoimmunity-against-dsdna-and-hsp60
#12
H Fausther-Bovendo, X Qiu, S McCorrister, G Westmacott, P Sandstrom, C Castilletti, A Di Caro, G Ippolito, G P Kobinger
Ebola virus (EBOV) survivors are affected by a variety of serious illnesses of unknown origin for years after viral clearance from the circulation. Identifying the causes of these persistent illnesses is paramount to develop appropriate therapeutic protocols. In this study, using mouse and non-human primates which survived EBOV challenge, ELISA, western blot, mass spectrometry and flow cytometry were used to screen for autoantibodies, identify their main targets, investigate the mechanism behind their induction and monitor autoantibodies accumulation in various tissues...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174261/identification-of-unique-antigenic-determinants-in-the-amino-terminus-of-ia-2-ica512-in-childhood-and-adult-autoimmune-diabetes-new-biomarker-development
#13
Maria Acevedo-Calado, Eddie A James, Michael P Morran, Susan L Pietropaolo, Qin Ouyang, David Arribas-Layton, Marco Songini, Marco Liguori, Anna Casu, Richard J Auchus, Shuai Huang, Liping Yu, Aaron Michels, Roberto Gianani, Massimo Pietropaolo
OBJECTIVE: The characterization of diverse subtypes of diabetes is a dynamic field of clinical research and an active area of discussion. The objective of this study was to identify new antigenic determinants in the neuroendocrine autoantigen IA-2 (ICA512) and assess whether circulating autoantibodies directed to new IA-2 epitopes identify autoimmune diabetes in young and adult populations with diabetes. RESEARCH DESIGN AND METHODS: Clinically diagnosed patients with type 2 diabetes (n = 258; diabetes duration: 0...
February 7, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28173777/microrna-29c-inhibits-cell-proliferation-by-targeting-nasp-in-human-gastric-cancer
#14
Beiqin Yu, Xuehua Chen, Jianfang Li, Qinlong Gu, Zhenggang Zhu, Chen Li, Liping Su, Bingya Liu
BACKGROUND: Gastric cancer is one of the most common malignancies worldwide. Recent studies have shown that microRNAs play crucial roles in regulating cellular proliferation process in gastric cancer. MicroRNA-29c (miR-29c) acts as a tumor suppressor in different kinds of tumors. METHODS: Quantitative PCR was performed to evaluate miR-29c expression level in 67 patient gastric cancer tissues and 9 gastric cancer cell lines. The effects of miR-29c were explored by proliferation assay, soft agar colony formation assay, apoptosis and cell cycle analysis using flow cytometry...
February 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28161237/low-molecular-weight-heparins-prevent-the-induction-of-autophagy-of-activated-neutrophils-and-the-formation-of-neutrophil-extracellular-traps
#15
Angelo A Manfredi, Patrizia Rovere-Querini, Armando D'Angelo, Norma Maugeri
The protection exerted by neutrophils against invading microbes is partially mediated via the generation of neutrophil extracellular traps (NETs). In sterile conditions NETs are damaging species, enriched in autoantigens and endowed with the ability to damage the vessel wall and bystander tissues, to promote thrombogenesis, and to impair wound healing. To identify and reposition agents that can be used to modulate the formation of NETs is a priority in the research agenda. Low molecular weight heparins (LMWH) are currently used, mostly on an empirical basis, in conditions in which NETs play a critical role, such as pregnancy complications associated to autoimmune disease...
February 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28152559/t-cell-responses-to-peptides-of-goodpasture-autoantigen-in-patients-with-anti-glomerular-basement-membrane-disease
#16
Shui-Yi Hu, Xiao-Yu Jia, Qiu-Hua Gu, Chong-Yan Yu, Xu-Yang Cheng, Qi-Zhuang Jin, Fu-de Zhou, Zhao Cui, Ming-Hui Zhao
AIM: Cell-mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti-glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti-GBM patients, aiming to identify the epitopes and their clinical significance. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 13 patients with anti-GBM disease. Twenty-four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1...
February 2, 2017: Nephrology
https://www.readbyqxmd.com/read/28149012/filarial-abundant-larval-transcript-protein-alt-2-an-immunomodulatory-therapeutic-agent-for-type-1-diabetes
#17
Sridhar M Reddy, Pooja M Reddy, Nitin Amdare, Vishal Khatri, Aaditya Tarnekar, Kalyan Goswami, Maryada Venkata Rami Reddy
Type 1 diabetes (T1D) that accounts for about 5-10 % of all diabetes cases results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. It is characterized by severe inflammatory reaction mediated by pronounced T helper type-1 response. Parasitic infections having the ability to skew the host immune responses towards type-2 type as a part of their defense mechanism are able to induce protection against autoimmune diseases like T1D. Hence, the present study is undertaken to explore a recombinant abundant larval transcript protein of the human lymphatic filarial parasite Brugia malayi (rBmALT-2), a known anti-inflammatory molecule for its therapeutic effect on streptozotocin (STZ)-induced T1D in mice...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28137667/identification-of-novel-autoantigens-via-mass-spectroscopy-based-antibody-mediated-identification-of-autoantigens-ms-amida-using-immune-thrombocytopenic-purpura-itp-as-a-model-disease
#18
Julian Kamhieh-Milz, Viktor Sterzer, Hatice Celik, Omid Khorramshahi, Reham Fadl Hassan Moftah, Abdulgabar Salama
Immune thrombocytopenic purpura (ITP) is one of the best characterized autoimmune diseases. Autoantibodies (AABs) against platelet antigens are considered as the diagnostic hallmark of ITP, but are detectable in only 50% of patients. We designed and applied a novel proteomic approach termed Mass Spectroscopy-based Antibody-Mediated Identification of Autoantigens (MS-AMIDA) for platelet antigens. Patients were separated into patients with classical AABs [ITP(+)] and patients without AABs [ITP(-)]. Altogether, 181 potential AAGs were found in ITP(+) and 135 AAGs in ITP(-), with 34 and 23 AAGs reproducibly found in two runs of MS-AMIDA...
January 27, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28135336/antibodies-directed-against-a-peptide-epitope-of-a-klebsiella-pneumoniae-derived-protein-are-present-in-ankylosing-spondylitis
#19
Antonio Puccetti, Marzia Dolcino, Elisa Tinazzi, Francesca Moretta, Salvatore D'Angelo, Ignazio Olivieri, Claudio Lunardi
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis of unknown origin. Its autoimmune origin has been suggested but never proven. Several reports have implicated Klebsiella pneumoniae as a triggering or perpetuating factor in AS; however, its role in the disease pathogenesis remains debated. Moreover, despite extensive investigations, a biomarker for AS has not yet been identified. To clarify these issues, we screened a random peptide library with pooled IgGs obtained from 40 patients with AS. A peptide (AS peptide) selected from the library was recognized by serum IgGs from 170 of 200 (85%) patients with AS but not by serum specimens from 100 healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28134083/direct-suppression-of-autoaggressive-cd8-t-cells-with-cd80-86-blockade-in-cd8-t-cell-mediated-polymyositis-models-of-mice
#20
Hisanori Hasegawa, Kimito Kawahata, Fumitaka Mizoguchi, Naoko Okiyama, Nobuyuki Miyasaka, Hitoshi Kohsaka
OBJECTIVES: CD80/86 blockade to inhibit CD28 costimulation suppressed alloreactive human and murine CD4+ T cells but not alloreactive CD8+ T cells. In contrast, CD28 costimulation augments CD8+ T cell-mediated cell lysis in antigen-nonspecific stimulation. The present study was conducted to discern whether the CD80/86 blockade exerts therapeutic effects on CD8+ T cell-mediated polymyositis (PM) models of mice and whether the effects could be attributable to direct suppression of autoantigen-specific CD8+ T cells...
January 27, 2017: Clinical and Experimental Rheumatology
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